Prevalence and Incidence of Rare Diseases

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Number 1 | January 2021

Prevalence and incidence of rare diseases:

Bibliographic data Prevalence, incidence or number of published cases listed by diseases (in alphabetical order)

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is favoured (registries, meta-analyses, population-based studies, Methodology large cohorts studies).

For congenital diseases, the prevalence is estimated, so that: Orphanet carries out a systematic survey of literature in order to Prevalence = birth prevalence x (patient life expectancy/general estimate the prevalence and incidence of rare diseases. This population life expectancy). study aims to collect new data regarding point prevalence, birth When only incidence data is documented, the prevalence is prevalence and incidence, and to update already published data estimated when possible, so that : according to new scientific studies or other available data. Prevalence = incidence x disease mean duration.

This data is presented in the following reports published When neither prevalence nor incidence data is available, which biannually: is the case for very rare diseases, the number of cases or families documented in the medical literature is provided. • Prevalence, incidence or number of published cases listed by diseases (in alphabetical order); Limitations of the study • Diseases listed by decreasing prevalence, incidence or number of published cases; The prevalence and incidence data presented in this report are only estimations and cannot be considered to be absolutely Data collection correct. The average values presented in this report do not take into A number of different sources are used : account the heterogeneous nature of the methodologies employed by the studies considered in the literature survey. • Registries (RARECARE, EUROCAT, etc) ; The validity and exactitude of raw data sources is taken for • National/international health institutes and agencies granted and have not been verified. Thus, confusion between (Institut National de Veille Sanitaire (French Institute terms such as incidence and prevalence and/or birth prevalence of Health Surveillance); American Center of Disease is possible due to the interchangeable use of these terms in Control and Prevention, American National Cancer certain sources. Institute, European Medicines Agency, World Health It is possible that prevalence is overestimated in some cases as Organization etc) ; epidemiological studies are generally based on hospital data in regions with higher prevalence. • Medline is consulted using the following search algorithm : «Disease names» AND Data presentation Epidemiology[MeSH:NoExp] OR Incidence[Title/abstract] OR Prevalence[Title/ abstract] OR Epidemiology[Title/abstract]; Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data • Medical texts, grey literature and reports from experts; I indicates incidence data. BP indicates birth prevalence • Orphanet collaborating experts Please note that this is just a selection of Orphanet's rare Data characteristics disease epidemiological data. Currently 6077 rare diseases are annotated with prevalence or incidence information in the The data published in this document are worldwide estimations, Orphanet database. To access the complete data sets visit or European estimations if a worldwide estimation is not Orphadata (www.orphadata.org). available.

The published data is raw collected data or extrapolations of raw data at worldwide or European level when no genetic founder effect is suspected as a cause of a disease.

If a range of national data is available, the average is calculated to estimate the worldwide or European prevalence or incidence.When a range of data sources is available, the most recent data source that meets a certain number of quality criteria

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Prevalence, incidence or number of of Estimated ORPHACod Disease publishe published cases listed by diseases (in prevalence/inciden e or Group of diseases d cases ce (/100,000) alphabetical order) or families 16p13.3 microduplication 27 Cases Number 96078 syndrome of Estimated 42 Cases ORPHACod Disease publishe 352629 16q24.1 microdeletion syndrome prevalence/inciden e or Group of diseases d cases ce (/100,000) 27 Cases or 261250 16q24.3 microdeletion syndrome

families 17p13.3 microduplication 50 Cases 11p15.4 microduplication 1 Family 217385 300305 syndrome syndrome 170

11q22.2q22.3 microdeletion 5 Cases 97685 17q11 microdeletion syndrome Cases 444002 syndrome 11 Cases 17q11.2 microduplication 7 Cases 313884 12p12.1 microdeletion syndrome 139474 syndrome 22 Cases 103 94063 12q14 microdeletion syndrome 261265 17q12 microdeletion syndrome Cases 12q15q21.1 microdeletion 6 Cases 289513 syndrome 118 17q12 microduplication 3 Cases 261272 Cases 412035 13q12.3 microdeletion syndrome syndrome

3 Cases 17q21.31 microdeletion 1.82 P* 261120 14q11.2 microdeletion syndrome 363958 syndrome 14q11.2 microduplication 7 Cases 17q23.1q23.2 microdeletion 7 Cases 261229 261279 syndrome syndrome 3 Cases 19 Cases 261144 14q12 microdeletion syndrome 529962 17q24.2 microdeletion syndrome

14q22q23 microdeletion 5 Cases 19p13.12 microdeletion 6 Cases 264200 254346 syndrome syndrome 14q24.1q24.3 microdeletion 3 Cases 19p13.13 microdeletion 7 Cases 401935 357001 syndrome syndrome 33 Cases 19p13.3 microduplication 6 Cases 488280 14q32 duplication syndrome 447980 syndrome 12 Cases 19q13.11 microdeletion 12 Cases 314585 15q overgrowth syndrome 217346 syndrome 200 9 Cases 261183 15q11.2 microdeletion syndrome Cases 293948 1p21.3 microdeletion syndrome

1p31p32 microdeletion 5 Cases 15q11q13 microduplication 30 Cases 401986 238446 syndrome syndrome 2 Cases 246 456298 1p35.2 microdeletion syndrome

199318 15q13.3 microdeletion syndrome Cases 1q21.1 microduplication 46 Cases 250994 syndrome 9 Cases 100 261190 15q14 microdeletion syndrome 238769 1q44 microdeletion syndrome Cases 30 Cases 94065 15q24 microdeletion syndrome 2-aminoadipic 2-oxoadipic 20 Cases 16p11.2p12.2 microdeletion 8 Cases 79154 261211 aciduria syndrome 2-methylbutyryl-CoA 30 Cases 16p11.2p12.2 microduplication 7 Cases 79157 261204 dehydrogenase deficiency syndrome 3 Cases 16p12.1p12.3 triplication 3 Cases 261295 20p12.3 microdeletion syndrome 485405 syndrome 4 Cases 16p13.11 microdeletion 7.0 BP 313781 20p13 microdeletion syndrome 261236 syndrome 11 Cases 162 444051 20q11.2 microdeletion syndrome 16p13.11 microduplication 261243 Cases 21q22.11q22.12 microdeletion 14 Cases syndrome 261323 syndrome 6 Cases 500055 16p13.2 microdeletion syndrome 567 22q11.2 deletion syndrome 9.6 BP*

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 3 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families syndrome 37.5 BP 7 Cases 567 22q11.2 deletion syndrome 397695 3q27.3 microdeletion syndrome

2 Cases 46,XX disorder of sex 363680 2p13.2 microdeletion syndrome 2 Cases 2975 development-skeletal anomalies

2p15p16.1 microdeletion 11 Cases syndrome 261349 syndrome 46,XX ovarian dysgenesis-short 3 Cases 444048 7 Cases stature syndrome 163693 2p21 microdeletion syndrome 500 46,XX ovotesticular disorder of 2p21 microdeletion syndrome 2 Cases 2138 Cases 369881 sex development without cystinuria 18 Cases 46,XX ovotesticular disorder of 2.5 BP 228402 2q23.1 microdeletion syndrome 2138 sex development 2q23.1 microduplication 2 Cases 46,XX testicular disorder of sex 2.5 P 313947 393 syndrome development 46,XY disorder of sex 23 Cases 15 Cases 1617 2q24 microdeletion syndrome 90796 development due to isolated

2q32q33 microdeletion 25 Cases 17,20-lyase deficiency 251019 46,XY disorder of sex 2 syndrome 115 443087 development due to testicular Families

1001 2q37 microdeletion syndrome Cases 17,20-desmolase deficiency

46,XY disorder of sex 3-hydroxy-3-methylglutaryl-CoA 9 Cases development-adrenal 9 Cases 35701 168558 synthase deficiency insufficiency due to CYP11A1 13 Cases deficiency 939 3-hydroxyisobutyric aciduria 46,XY gonadal dysgenesis-motor 5 Cases 3-methylcrotonyl-CoA 2.65 BP* 168563 and sensory neuropathy 6 carboxylase deficiency syndrome 3-methylglutaconic aciduria type 20 Cases 50.0 BP* 67046 8 47,XYY syndrome 1 3-methylglutaconic aciduria type 22 Cases 1.0 BP* 445038 96263 48,XXXY syndrome 7 3-methylglutaconic aciduria type 9 Cases 1.9 BP* 505208 10 48,XXYY syndrome 8 3-methylglutaconic aciduria type 4 Cases 10 Cases 505216 99329 48,XYYY syndrome 9 3-phosphoglycerate 0.55 BP* 15 Cases 96264 49,XXXXY syndrome 79351 dehydrogenase deficiency, 2 Cases infantile/juvenile form 261534 49,XXXYY syndrome 3-phosphoserine phosphatase 8 Cases 79350 deficiency, infantile/juvenile 8 Cases 99330 49,XYYYY syndrome form 200 25 Cases 7 3C syndrome 289494 4H leukodystrophy Cases

200

2616 3M syndrome Cases 14 Cases 238750 4q21 microdeletion syndrome

32 Cases 4q25 proximal deletion 3 Cases 293843 3MC syndrome 502437 syndrome 8 Cases 2.0 P* 435638 3p25.3 microdeletion syndrome 217064 5-fluorouracil poisoning

42 Cases 8 Cases 1621 3q13 microdeletion syndrome 33572 5-oxoprolinase deficiency

100 7 Cases 329802 5p13 microduplication syndrome 96095 3q26 microduplication syndrome Cases 40 Cases 228384 5q14.3 microdeletion syndrome 356947 3q26q27 microdeletion 4 Cases 228415 5q35 microduplication syndrome 30 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 4 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families syndrome 19 Cases 9 251046 6p22 microdeletion syndrome 100008 ACys amyloidosis Families

19 Cases 75857 6q terminal deletion syndrome 50 Cases 978 ADULT syndrome 12 Cases 171829 6q16 microdeletion syndrome 475

4 Cases 85448 AGel amyloidosis Cases 251056 6q25 microdeletion syndrome

7p22.1 microduplication 5 Cases 12 Cases 314034 442582 AH amyloidosis syndrome 163 AHDC1-related intellectual 7q11.23 microduplication 96121 Cases disability-obstructive sleep 4 Cases syndrome 412069 apnea-mild dysmorphism 20 Cases syndrome 251061 7q31 microdeletion syndrome 4 Cases 250977 AICA-ribosiduria 8p inverted duplication/deletion 3.9 BP* 96092 20.0 P* syndrome 90081 AIDS wasting syndrome 3 Cases 251066 8p11.2 deletion syndrome AKT2-related familial partial 1 Family 79085 1.72 P lipodystrophy 251076 8p23.1 duplication syndrome 10.0 P* 85443 AL amyloidosis 4 Cases 228399 8q12 microduplication syndrome ALDH18A1-related De Barsy 32 Cases 35664 13 Cases syndrome 284160 8q21.11 microdeletion syndrome 57 Cases 79327 ALG1-CDG 6 Cases 178303 8q22.1 microdeletion syndrome 8 Cases 280071 ALG11-CDG 2 Cases 508488 8q24.3 microdeletion syndrome 11 Cases 79324 ALG12-CDG 4 Cases 324313 9p13 microdeletion syndrome 1 Case 324422 ALG13-CDG 10 Cases 531151 9q21.13 microdeletion syndrome 1 Case 79326 ALG2-CDG 9q31.1q31.3 microdeletion 2 Cases 401923 15 Cases syndrome 79321 ALG3-CDG 9q33.3q34.11 microdeletion 4 Cases 495818 54 Cases syndrome 79320 ALG6-CDG 2 Cases 439232 AApoAIV amyloidosis 15 Cases 79325 ALG8-CDG 1 Family 324723 ABeta amyloidosis, Arctic type 12 Cases 79328 ALG9-CDG 250 7 100006 ABeta amyloidosis, Dutch type Cases 93561 ALys amyloidosis Families

324708 ABeta amyloidosis, Iowa type Families 5 Cases 157954 ANE syndrome

7 ANGPT1-related hereditary 4 Cases 537891 324713 ABeta amyloidosis, Italian type Families angioedema with normal C1Inh

ANK3-related intellectual 5 Cases 2 356996 disability-sleep disturbance

324718 ABetaA21G amyloidosis Families syndrome

3 Cases 1133 AREDYLD syndrome 1 Family 324703 ABetaL34V amyloidosis ATP13A2-related juvenile 4 Cases 314632 99892 ACTH-dependent Cushing 0.55 I neuronal ceroid lipofuscinosis

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 5 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 4 0.08 I AXIN2-related attenuated 73274 Acquired hemophilia 401911 Families familial adenomatous polyposis Acquired hypertrichosis 60 Cases 2221 0.5 BP* lanuginosa 915 Aarskog-Scott syndrome Acquired idiopathic sideroblastic 0.09 I* 75564 10 Cases anemia 916 Aase-Smith syndrome 242

100 464453 Acquired methemoglobinemia Cases

14 Abetalipoproteinemia Cases

Acquired monoclonal Ig light 100

Ablepharon macrostomia 16 Cases 91136 chain-associated Fanconi Cases 920 syndrome syndrome 200 Acquired pseudoxanthoma 20 Cases Abnormal origin of right or left 228247 99050 Cases elasticum pulmonary artery from the aorta 300 Acquired von Willebrand 4 Cases 99147 Cases 921 Abruzzo-Erickson syndrome syndrome

Absence deformity of leg- 2 Cases 10 2310 Acral dystrophic epidermolysis cataract syndrome 158673 Families bullosa 10 Absence of fingerprints- 1658 Families 40 Cases congenital milia syndrome 263534 Acral peeling skin syndrome

0.5 I* 2 Cases 980 Absence of the pulmonary artery 281127 Acral self-healing collodion baby

Absent radius-anogenital 2 Cases 10 Cases 3016 958 Acro-renal-mandibular syndrome anomalies syndrome Absent thumb-short stature- 3 Cases 20 2951 immunodeficiency syndrome 959 Acro-renal-ocular syndrome Families

Absent tibia-polydactyly- 3 Cases 3328 arachnoid cyst syndrome 38 Cases 36 Acrocallosal syndrome Acanthosis nigricans-insulin 5 Cases 90301 resistance-muscle cramps-acral 10 Cases 2008 Acrocardiofacial syndrome enlargement syndrome 3.2 P* 8 Cases 926 Acatalasemia 221054 Acrocephalopolydactyly

0.09 P 2 Cases 48818 Aceruloplasminemia 949 Acrocraniofacial dysostosis

Achalasia-microcephaly 7 Cases 80 Cases 929 950 Acrodysostosis syndrome 4.0 BP Acrodysostosis with multiple 40 Cases 15 Achondroplasia 280651 hormone resistance 3.0 BP* 2 Cases 15 Achondroplasia 2956 Acrodysplasia scoliosis

2.7 P 2 49382 Achromatopsia Acrofacial dysostosis, Catania 1786 Families type 0.029 I* 424046 Acinar cell carcinoma of pancreas Acrofacial dysostosis, Kennedy- 2 Cases 64542 Acitretin/etretinate 26 Cases Teebi type 40366 embryopathy Acrofacial dysostosis, Palagonia 4 Cases 1787 Acquired aneurysmal 10.0 P* type 90065 subarachnoid hemorrhage Acrofacial dysostosis, Rodríguez 13 Cases 1788 200 type

91385 Acquired angioedema Cases 12 Cases 1784 Acrofrontofacionasal dysostosis

Acquired generalized 1.0 P* Acromegaloid facial appearance 23 Cases 79086 965 lipodystrophy syndrome 0.1 P* 0.47 I 73274 Acquired hemophilia 963 Acromegaly

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 6 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

22 Cases 11.0 P* 1827 Acromelic frontonasal dysplasia 513 Acute lymphoblastic leukemia

Acromesomelic dysplasia, 10 Cases 101 968 Hunter-Thompson type 488239 Acute macular neuroretinopathy Cases

Acromesomelic dysplasia, 50 Cases 40 Maroteaux type Acute megakaryoblastic 0.02 I* 518 60 Cases leukemia 969 Acromicric dysplasia Acute monoblastic/monocytic 0.13 I* 514 100 leukemia

955 Acroosteolysis dominant type Cases Acute myeloblastic leukemia 0.02 I* 98834 with maturation Acroosteolysis-keloid-like Acute myeloblastic leukemia 0.01 I* 5 Cases 98833 363665 lesions-premature aging without maturation

syndrome 2.5 I 519 Acute myeloid leukemia 25 Cases 85203 Acropectoral syndrome 3.39 I* 519 Acute myeloid leukemia 30 Cases 957 Acropectorovertebral dysplasia 10.0 P* 519 Acute myeloid leukemia 20 Cases 971 Acrorenal syndrome 10.98 519 Acute myeloid leukemia Action myoclonus-renal failure 38 Cases 163696 syndrome Acute myeloid leukemia with 0.01 I* 98832 18 Cases minimal differentiation 397596 Activated PI3K-delta syndrome Acute myeloid leukemia with 0.11 I* 98277 12 Cases recurrent genetic anomaly 284460 Acute annular outer retinopathy 0.17 I* 517 Acute myelomonocytic leukemia Acute disseminated 0.6 I* 83597 encephalomyelitis Acute panmyelosis with 0.06 I* 86843 Acute encephalopathy with 283 myelofibrosis

363549 biphasic seizures and late Cases Acute peripheral arterial 16.0 P* 90064 reduced diffusion occlusion Acute generalized 0.3 I 0.11 I* 293173 520 Acute promyelocytic leukemia exanthematous pustulosis Acute infantile liver failure due 19 Cases Acute sensorineural hearing loss 217371 to synthesis defect of mtDNA- by acute acoustic trauma or 40.0 P* 90059 encoded proteins sudden deafness or surgery Acute infantile liver failure- induced acoustic trauma cerebellar ataxia-peripheral 3 Cases 1.6 I 466794 139417 Acute transverse myelitis sensory motor neuropathy syndrome 150 Acute infantile liver failure- Acute zonal occult outer 6 Cases 284454 Cases 370088 multisystemic involvement retinopathy

syndrome Acyl-CoA dehydrogenase 9 23 Cases Acute inflammatory 99901 3.1 P* deficiency 98916 demyelinating 0.01 I* 55881 Adamantinoma polyradiculoneuropathy 0.013 I* 0.11 79276 Acute intermittent porphyria 55881 Adamantinoma

0.54 P* 398 79276 Acute intermittent porphyria 974 Adams-Oliver syndrome Cases 3.8 P* 79126 Acute interstitial pneumonia 12.5 P* 20.0 P* 85138 Addison disease 90062 Acute liver failure Adducted thumbs-arthrogryposis 9 Cases 25.0 I* 2952 178320 Acute lung injury syndrome, Christian type

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 7 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 5.97 I* 213504 Adenocarcinoma of ovary Agammaglobulinemia- 3 Cases Adenocarcinoma of the anal 0.253 I* 83617 microcephaly-craniosynostosis- 424016 canal severe dermatitis syndrome Adenocarcinoma of the cervix 1.01 I* 10.0 P* 213772 51 Aicardi-Goutières syndrome uteri Adenocarcinoma of the 3.264 I* Alacrimia-choreoathetosis-liver 8 Cases 99976 404454 esophagus dysfunction syndrome Adenocarcinoma of the 0.7 I 0.8 BP* 99976 52 Alagille syndrome esophagus Adenocarcinoma of the 5.55 Alar cartilages hypoplasia- 2 Cases 99976 2007 esophagus coloboma-telecanthus syndrome Adenocarcinoma of the 10 Cases 2.62 I* 319671 Alazami syndrome 424991 gallbladder and extrahepatic

biliary tract 1.0 P 53 Albers-Schönberg osteopetrosis Adenocarcinoma of the liver and 0.412 I* 424943 intrahepatic biliary tract 5.0 P* 53 Albers-Schönberg osteopetrosis Adenocarcinoma of the small 0.588 I* 104075 intestine 1 Family 998 Albinism-deafness syndrome 100 Adenosine monophosphate 45 Cases 2 Cases deaminase deficiency 502444 Alkaline ceramidase 3 deficiency

Adenovirus infection in 18.0 P* 320 91127 immunocompromised patients 59 Allan-Herndon-Dudley syndrome Cases

Adenylosuccinate lyase 56 Cases 46 deficiency 3 Cases 1006 Alopecia antibody deficiency Adenylosuccinate synthetase-like 19 Cases 482601 1-related distal myopathy 10.5 P* 700 Alopecia totalis 0.75 P* 1501 Adrenocortical carcinoma 25.0 P* 701 Alopecia universalis 0.03 I* 1501 Adrenocortical carcinoma Alopecia-contractures-dwarfism- 5 Cases 1005 2 Cases intellectual disability syndrome 977 Adrenomyodystrophy Alopecia-epilepsy-pyorrhea- 12 Cases 1008 3.0 P* intellectual disability syndrome 86875 Adult T-cell leukemia/lymphoma 15 Alopecia-intellectual disability Adult familial nephronophthisis- 2 Cases 2850 Families 2666 syndrome spastic quadriparesia syndrome 19 Cases Alopecia-intellectual disability- 178487 Adult intestinal botulism 2 Cases 1014 hypergonadotropic

50 Cases hypogonadism syndrome 206583 Adult polyglucosan body disease 0.7 BP* 726 Alpers-Huttenlocher syndrome 20 Adult-onset autosomal dominant 99027 Families 0.07 P* leukodystrophy 726 Alpers-Huttenlocher syndrome

Adult-onset autosomal recessive 14 Cases 20.0 P* 284289 60 Alpha-1-antitrypsin deficiency cerebellar ataxia Adult-onset autosomal recessive 2 Cases Alpha-B crystallin-related late- 17 Cases 255132 399058 sideroblastic anemia onset myopathy 2 Alpha-N-acetylgalactosaminidase 20 Cases Adult-onset cervical dystonia, 3137 420492 Families deficiency DYT23 type Alpha-N-acetylgalactosaminidase 10 Cases 79279 Adult-onset distal myopathy due 9 Cases deficiency type 1 329478 to VCP mutation Alpha-N-acetylgalactosaminidase 10 Cases 79280 Adult-onset dystonia- 14 Cases deficiency type 2 199351 parkinsonism Alpha-N-acetylgalactosaminidase 10 Cases 79281 183669 Agammaglobulinemia 0.13 P* deficiency type 3

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 8 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Alpha-dystroglycan-related limb- 1 Case 0.1 I* 280333 37553 Andersen-Tawil syndrome girdle muscular dystrophy R16 400 Aneurysm-osteoarthritis 45 Cases 284984 100025 Alpha-heavy chain disease Cases syndrome

Angel-shaped phalango- 20 Cases 63442 0.1 P* epiphyseal dysplasia 61 Alpha-mannosidosis 7.5 P 72 Angelman syndrome 200 Alpha-thalassemia-X-linked 847 Cases 1.3 BP* intellectual disability syndrome 72 Angelman syndrome

Alpha-thalassemia-intellectual 20 Cases 52 Cases 98791 disability syndrome linked to 251671 Angiocentric glioma

chromosome 16 Angioosteohypertrophic 0.8 BP* Alpha-thalassemia- 80 Cases 2346 231401 syndrome myelodysplastic syndrome 0.02 Alport syndrome-intellectual 2 263413 Angiosarcoma

86818 disability-midface hypoplasia- Families 2 Cases 370039 Angora hair nevus elliptocytosis syndrome 950 Anhidrotic ectodermal dysplasia- 64 Alström syndrome Cases immunodeficiency- 2 Cases 69088 osteopetrosis-lymphedema 0.16 I* 284 Alveolar echinococcosis syndrome 3 Cases Amaurosis-hypertrichosis 2 Cases 1069 Aniridia-absent patella syndrome 1021 syndrome 22 Aniridia-cerebellar ataxia- Amelo-onycho-hypohidrotic 2 Cases 1065 Families 1028 intellectual disability syndrome syndrome 40 Cases Aniridia-intellectual disability 2 Cases 314422 Ameloblastic carcinoma 1068 syndrome Aminopterin/methotrexate 17 Cases Aniridia-ptosis-intellectual 1908 3 Cases embryofetopathy 1067 disability-familial obesity

1.0 P* syndrome 67043 Amoebic keratitis Aniridia-renal agenesis- 2 Cases 27 Cases 1064 psychomotor retardation 319635 Amyloidosis cutis dyschromia syndrome 2.2 I* 0.32 I 803 Amyotrophic lateral sclerosis 1070 Anisakiasis

3.85 P Ankyloblepharon filiforme 3 803 Amyotrophic lateral sclerosis 1074 adnatum-imperforate anus Families

5.2 P* syndrome 803 Amyotrophic lateral sclerosis Ankylosing vertebral 8 Cases 2206 1.35 I hyperostosis with tylosis 803 Amyotrophic lateral sclerosis 10 Cases 254411 Annular atrophic lichen planus Amyotrophic lateral sclerosis 70 Cases 357043 type 4 7

18.3 P* 281139 Annular epidermolytic ichthyosis Families 228113 Anal fistula

2.0 P* 1.8 BP* 98841 Anaplastic large cell lymphoma 675 Annular pancreas

0.09 I* Anonychia with flexural 3 Cases 251630 Anaplastic oligodendroglioma 69125 pigmentation 0.17 I* Anonychia-microcephaly 4 Cases 142 Anaplastic thyroid carcinoma 1094 syndrome 0.1 P* Anonychia-onychodystrophy 14 Cases 142 Anaplastic thyroid carcinoma 90390 syndrome 10 Cases 17 Cases 93347 Anauxetic dysplasia 1104 Anophthalmia plus syndrome

1101 Anophthalmia-megalocornea- 3 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 9 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families cardiopathy-skeletal anomalies 1.0 P* 23 Argininosuccinic aciduria syndrome Anophthalmia/microphthalmia- 30 Cases 38 Cases 77298 91 Aromatase deficiency esophageal atresia syndrome 0.028 BP* 30 Cases 93976 Anotia 178345 Aromatase excess syndrome

11 Cases 140 2987 Antecubital pterygium syndrome Aromatic L-amino acid 35708 Cases decarboxylase deficiency Anterior maxillary protrusion- 7 Cases 562559 strabismus-intellectual disability Arrhinia-choanal atresia- 4 Cases 1135 syndrome microphthalmia syndrome Anti-glomerular basement 0.08 I* Arrhythmogenic right ventricular 20.0 P 375 247 membrane disease cardiomyopathy Anti-glomerular basement 0.2 P* Arterial dissection-lentiginosis 4 Cases 375 1682 membrane disease syndrome 50 Cases 102 454710 Anti-p200 pemphigoid 3342 Arterial tortuosity syndrome Cases

3.5 P 81 Antisynthetase syndrome Arthrogryposis multiplex 5.7 BP* 1037 34 Cases congenita 83 Antley-Bixler syndrome Arthrogryposis multiplex 10 Cases 35.6 BP* 1150 congenita-whistling face 1457 Aorta coarctation syndrome Aortic arch anomaly-facial Arthrogryposis-anterior horn cell 15 Cases 4 Cases 53696 1110 dysmorphism-intellectual disease syndrome

disability syndrome Arthrogryposis-ectodermal 2 Cases 3200 0.3 BP* dysplasia syndrome 2299 Aortic arch interruption Arthrogryposis-hyperkeratosis 2 Cases 1485 130 syndrome, lethal form

3400 Aorto-ventricular tunnel Cases Arthrogryposis-like hand 1 Family 1144 anomaly-sensorineural deafness

Aphalangy-hemivertebrae- syndrome 3 Cases 1112 urogenital-intestinal dysgenesis Arthrogryposis-renal 100

syndrome 2697 dysfunction-cholestasis Cases

Aphalangy-syndactyly- 5 Cases syndrome 1113 microcephaly syndrome 2 Arthrogryposis-severe scoliosis Aphonia-deafness-retinal 65720 Families 2 Cases syndrome 324540 dystrophy-bifid halluces-

intellectual disability syndrome 50 Cases 1253 Ascher syndrome 10.0 BP 1114 Aplasia cutis congenita 44.0 P* 137686 Asherman syndrome Aplasia cutis congenita-intestinal 3 Cases 1116 lymphangiectasia syndrome 5 Cases 85175 Astley-Kendall dysplasia 4 Cases 1117 Aplasia cutis-myopia syndrome 0.02 I* 251679 Astroblastoma 8.5 P* 99981 Apnea of prematurity 4.8 I* 94 Astrocytoma 30

425 Apolipoprotein A-I deficiency Families 2.5 P* 94 Astrocytoma

Aprosencephaly cerebellar 2 Cases 0.33 P* 1126 96 Ataxia with vitamin E deficiency dysgenesis Arachnodactyly-abnormal Ataxia-deafness-intellectual 8 Cases 5 Cases 1188 1129 ossification-intellectual disability disability syndrome

syndrome Ataxia-intellectual disability- 7 Cases Arachnodactyly-intellectual 370022 oculomotor apraxia-cerebellar 3 Cases 1130 disability-dysmorphism cysts syndrome

syndrome 459033 Ataxia-oculomotor apraxia type 12 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 10 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Ataxia-photosensitivity-short 2 Cases 114 Auriculoosteodysplasia Families 1184 stature syndrome 0.49 P* Autism spectrum disorder due to 60 Cases 100 Ataxia-telangiectasia 352490 AUTS2 deficiency Autism spectrum disorder- 25 Cases 8 Cases 56304 Atelosteogenesis type II 370943 epilepsy-arthrogryposis

25 Cases syndrome 56305 Atelosteogenesis type III Autism-epilepsy syndrome due 5

Athabaskan brainstem 13 Cases 308410 to branched chain ketoacid Families 69739 dysgenesis syndrome dehydrogenase kinase deficiency Atherosclerosis-deafness- Autism-facial port-wine stain 4 Cases 2 Cases 137911 1192 diabetes-epilepsy-nephropathy syndrome 170 syndrome Autoerythrocyte sensitization 3.5 P* 324636 Cases 95713 Athyreosis syndrome

Autoimmune encephalopathy 14 Cases 10 Cases 1193 Atkin-Flaitz syndrome 420789 with parasomnia and obstructive

15.0 P* sleep apnea 163934 Atopic keratoconjunctivitis Autoimmune enteropathy and 5 Cases 16.0 BP* 391487 endocrinopathy-susceptibility to 1201 Atresia of small intestine chronic infections syndrome Atrial septal defect- 2.02 I* 11 Cases 98375 Autoimmune hemolytic anemia 1479 atrioventricular conduction

defects syndrome Autoimmune hemolytic anemia- Atrioventricular defect- autoimmune thrombocytopenia- 6 Cases 2 Cases 444463 1352 blepharophimosis-radial and primary immunodeficiency

anal defect syndrome syndrome 100 1.2 I Attenuated Chédiak-Higashi 2137 Autoimmune hepatitis 352723 Cases syndrome 0.75 I* 2137 Autoimmune hepatitis Atypical Fanconi syndrome- 7 Cases 544628 neonatal hyperinsulinism 23.5 P 2137 Autoimmune hepatitis syndrome 5 9 Cases Autoimmune interstitial lung 314466 Atypical Meigs syndrome 444092 Families disease-arthritis syndrome 0.17 BP* 1456 Atypical coarctation of aorta 500 Autoimmune Atypical dentin dysplasia due to 4 Cases 3261 Cases 314721 lymphoproliferative syndrome SMOC2 deficiency Autoimmune 20 Cases 17 Cases 289863 Atypical glycine encephalopathy 436159 lymphoproliferative syndrome

due to CTLA4 haploinsuffiency Atypical hemolytic uremic 1.0 P* 2134 Autoimmune syndrome 1 Family 275517 lymphoproliferative syndrome Atypical hypotonia-cystinuria 2 Cases 238523 with recurrent viral infections syndrome Autoimmune pulmonary alveolar 0.5 P 6 747 proteinosis 391411 Atypical juvenile parkinsonism Families Autoimmune pulmonary alveolar 0.04 I 747 proteinosis 20 Cases 86797 Atypical lichen myxedematosus Autoinflammation-PLCG2- 2 Cases 324530 associated antibody deficiency- Auditory neuropathy-optic 8 Cases 542585 immune dysregulation atrophy syndrome Autoinflammatory syndrome Auricular abnormalities-cleft lip 5 Cases 2 Cases 329173 with pyogenic bacterial infection 77300 with or without cleft palate- and amylopectinosis ocular abnormalities syndrome 100 50 Cases 33110 Autosomal agammaglobulinemia 137888 Auriculocondylar syndrome Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 11 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 50 Cases 90348 Autosomal dominant cutis laxa Autosomal dominant Charcot- 2 Cases 487814 Marie-Tooth disease type 2 due Autosomal dominant deafness- 22 Cases 79499 to DGAT2 mutation onychodystrophy syndrome Autosomal dominant Charcot- Autosomal dominant distal 2 Cases 8 Cases 435819 Marie-Tooth disease type 2 due 476093 axonal motor neuropathy-

to TFG mutation myofibrillar myopathy syndrome Autosomal dominant Charcot- 2 Autosomal dominant focal 28 Cases 329466 401964 Marie-Tooth disease type 2 with Families dystonia, DYT25 type

giant axons Autosomal dominant focal non- Autosomal dominant Charcot- 1 Family epidermolytic palmoplantar 21 Cases 99946 402003 Marie-Tooth disease type 2A1 keratoderma with plantar Autosomal dominant Charcot- 44 Cases blistering 99938 Marie-Tooth disease type 2D Autosomal dominant hyper-IgE 0.1 I* 2314 Autosomal dominant Charcot- 51 Cases syndrome 521414 Marie-Tooth disease type 2DD Autosomal dominant 40 Cases 5 1810 hypohidrotic ectodermal Autosomal dominant Charcot- 99940 Families dysplasia Marie-Tooth disease type 2F 100 Autosomal dominant Autosomal dominant Charcot- 1 Family 89937 Cases 99941 hypophosphatemic rickets Marie-Tooth disease type 2G Autosomal dominant intellectual Autosomal dominant Charcot- 30 Cases 16 Cases 99944 457193 disability-craniofacial anomalies- Marie-Tooth disease type 2K Autosomal dominant Charcot- 1 Family cardiac defects syndrome 99945 Autosomal dominant Marie-Tooth disease type 2L 20 Cases Autosomal dominant Charcot- 20 Cases 100043 intermediate Charcot-Marie- 228179 Marie-Tooth disease type 2M Tooth disease type A Autosomal dominant Autosomal dominant Charcot- 28 Cases 37 Cases 228174 100044 intermediate Charcot-Marie- Marie-Tooth disease type 2N Autosomal dominant Charcot- 8 Cases Tooth disease type B 329258 Autosomal dominant Marie-Tooth disease type 2Q 35 Cases Autosomal dominant Charcot- 2 Cases 100045 intermediate Charcot-Marie- 397735 Marie-Tooth disease type 2U Tooth disease type C Autosomal dominant Autosomal dominant Charcot- 21 Cases 12 Cases 447964 100046 intermediate Charcot-Marie- Marie-Tooth disease type 2V Tooth disease type D Autosomal dominant Charcot- 24 Cases 488333 Autosomal dominant Marie-Tooth disease type 2W 21 Cases 93114 intermediate Charcot-Marie- Autosomal dominant Charcot- 7 Cases 435387 Tooth disease type E Marie-Tooth disease type 2Y Autosomal dominant Autosomal dominant Charcot- 21 Cases 8 Cases 466768 352670 intermediate Charcot-Marie- Marie-Tooth disease type 2Z Tooth disease type F 100 Autosomal dominant Robinow Autosomal dominant 3107 Cases syndrome intermediate Charcot-Marie- 9 Cases 324585 Tooth disease with neuropathic Autosomal dominant adult-onset 0.1 P* 209335 pain proximal spinal muscular atrophy 4 Autosomal dominant aplasia and 6 Cases Autosomal dominant limb-girdle 314399 266 Families myelodysplasia muscular dystrophy type 1A

Autosomal dominant cerebellar 2.7 P 99 Autosomal dominant limb-girdle 11 Cases ataxia 238755 muscular dystrophy type 1H Autosomal dominant cerebellar 5.6 P* 99 100 ataxia Autosomal dominant 140957 Cases Autosomal dominant cerebellar macrothrombocytopenia 24 Cases 314404 ataxia-deafness-narcolepsy Autosomal dominant mendelian syndrome susceptibility to mycobacterial 68 Cases Autosomal dominant childhood- 319581 97 Cases diseases due to partial 363447 onset proximal spinal muscular IFNgammaR1 deficiency atrophy

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 12 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Autosomal dominant mendelian nerve conduction velocity susceptibility to mycobacterial 2 Cases Autosomal dominant spastic 53 Cases 319589 251282 diseases due to partial ataxia type 1 IFNgammaR2 deficiency 10 Autosomal dominant Autosomal dominant spastic 15 Cases 100991 Families 457050 mitochondrial myopathy with paraplegia type 10

exercise intolerance Autosomal dominant spastic 27 Cases Autosomal dominant multiple 4 Cases 100993 65743 paraplegia type 12 pterygium syndrome Autosomal dominant spastic 10 Cases 2 100994 Autosomal dominant paraplegia type 13 99846 Families 20 myoglobinuria Autosomal dominant spastic 100998 Families paraplegia type 17 Autosomal dominant myopia- midfacial retrusion-sensorineural 1 Family Autosomal dominant spastic 1 Family 440354 100999 hearing loss-rhizomelic dysplasia paraplegia type 19 syndrome Autosomal dominant spastic 1 Family Autosomal dominant 101009 99 Cases paraplegia type 29 329211 neovascular inflammatory Autosomal dominant spastic 1 Family 320365 vitreoretinopathy paraplegia type 36 100 Autosomal dominant nocturnal Autosomal dominant spastic 13 Cases 98784 Families 171612 frontal lobe epilepsy paraplegia type 37

Autosomal dominant spastic 1 Family Autosomal dominant optic 3.3 P 171617 98672 paraplegia type 38 atrophy Autosomal dominant spastic 7 Cases 3 320355 Autosomal dominant optic paraplegia type 41 67036 Families atrophy and cataract Autosomal dominant spastic 1 Family 171863 paraplegia type 42 Autosomal dominant optic 0.4 P* 1215 10 atrophy plus syndrome Autosomal dominant spastic 100988 Families Autosomal dominant optic 2.0 P paraplegia type 6 98673 atrophy, classic form Autosomal dominant spastic 1 Family Autosomal dominant 33 Cases 444099 2783 paraplegia type 73 osteopetrosis type 1 10 Autosomal dominant Autosomal dominant spastic 10 Cases 100989 Families 1010 palmoplantar keratoderma and paraplegia type 8

congenital alopecia 2 Autosomal dominant spastic Autosomal dominant polycystic 39.6 P* 447753 Families 730 paraplegia type 9A kidney disease Autosomal dominant polycystic 3 30 Cases Autosomal dominant spastic 88924 kidney disease type 1 with 447757 Families paraplegia type 9B tuberous sclerosis 200 Autosomal dominant popliteal Autosomal dominant striatal 11 Cases 1300 Cases 228169 pterygium syndrome neurodegeneration

Autosomal dominant 4 Autosomal dominant preaxial 1 Family 466806 thrombocytopenia with platelet Families 476119 polydactyly-upperback secretion defect hypertrichosis syndrome Autosomal dominant 3 Cases Autosomal dominant primary 3086 28 Cases vitreoretinochoroidopathy 34528 hypomagnesemia with Autosomal erythropoietic 0.012 I* hypocalciuria 79278 protoporphyria Autosomal dominant progressive 14 Cases 88659 Autosomal erythropoietic 0.92 P* nephropathy with hypertension 79278 protoporphyria Autosomal dominant proximal 1 Family 314889 Autosomal recessive Charcot- 29 Cases renal tubular acidosis 466775 Marie-Tooth disease type 2X Autosomal dominant 38 Cases 100 209867 rhegmatogenous retinal Autosomal recessive Robinow 1507 Cases detachment syndrome

140481 Autosomal dominant slowed 1 Family 250984 Autosomal recessive Stickler 15 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 13 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families syndrome deficiency 3 Cases Autosomal recessive congenital 0.5 P* 1027 Autosomal recessive amelia 281097 ichthyosis Autosomal recessive anterior 8 Cases Autosomal recessive cutis laxa 60 Cases 519388 90349 segment dysgenesis type 1 Autosomal recessive ataxia due 6 Cases Autosomal recessive cutis laxa 40 Cases 247815 90350 to PEX10 deficiency type 2 Autosomal recessive ataxia due 31 Cases Autosomal recessive dopa- 50 Cases 139485 101150 to ubiquinone deficiency responsive dystonia Autosomal recessive ataxia, 57 Cases Autosomal recessive 26 Cases 88644 1974 Beauce type faciodigitogenital syndrome Autosomal recessive axonal Autosomal recessive 7 Cases 2 Cases 329329 521411 Charcot-Marie-Tooth disease due frontotemporal pachygyria

to copper metabolism defect Autosomal recessive infantile 12 Cases 300547 33 hypercalcemia Autosomal recessive axonal 324442 Families Autosomal recessive 8 neuropathy with neuromyotonia 217055 intermediate Charcot-Marie- Families

Autosomal recessive 20 Cases Tooth disease type A 139455 bestrophinopathy Autosomal recessive 1 Case Autosomal recessive 20 Cases 254334 intermediate Charcot-Marie- 448242 brachyolmia Tooth disease type B Autosomal recessive cerebellar 3.3 P Autosomal recessive 1172 3 Cases ataxia 369867 intermediate Charcot-Marie-

Autosomal recessive cerebellar 3.6 P* Tooth disease type C 1172 ataxia Autosomal recessive 4 Cases Autosomal recessive cerebellar 435998 intermediate Charcot-Marie- 2 Cases 453521 ataxia due to CWF19L1 Tooth disease type D

deficiency Autosomal recessive isolated 5 Cases 98676 10 optic atrophy Autosomal recessive cerebellar 412057 Families Autosomal recessive lethal ataxia due to STUB1 deficiency 13 Cases 538096 neonatal axonal sensorimotor

Autosomal recessive cerebellar 10 Cases polyneuropathy 352641 ataxia with late-onset spasticity Autosomal recessive leukoencephalopathy-ischemic 3 Cases Autosomal recessive cerebellar 314572 ataxia-epilepsy-intellectual 2 Cases stroke-retinitis pigmentosa 404499 disability syndrome due to syndrome RUBCN deficiency Autosomal recessive lower 5 Cases 206580 motor neuron disease with Autosomal recessive cerebellar ataxia-epilepsy-intellectual 3 Cases childhood onset 404493 disability syndrome due to TUD Autosomal recessive malignant 0.75 BP* 667 deficiency osteopetrosis Autosomal recessive cerebellar Autosomal recessive mendelian ataxia-pyramidal signs- 17 Cases susceptibility to mycobacterial 7 Cases 363429 477857 nystagmus-oculomotor apraxia diseases due to complete syndrome RORgamma receptor deficiency Autosomal recessive cerebellar Autosomal recessive mendelian 1 Family 95434 ataxia-saccadic intrusion susceptibility to mycobacterial 18 Cases 319569 syndrome diseases due to partial Autosomal recessive cerebral 4 Cases IFNgammaR1 deficiency 363969 atrophy Autosomal recessive mendelian Autosomal recessive complex susceptibility to mycobacterial 6 Cases 4 Cases 319574 506353 spastic paraplegia due to diseases due to partial

Kennedy pathway dysfunction IFNgammaR2 deficiency Autosomal recessive congenital Autosomal recessive multiple 64 Cases 7 Cases 2990 363432 cerebellar ataxia due to GRID2 pterygium syndrome

deficiency Autosomal recessive myogenic 1 Family Autosomal recessive congenital 10 Cases 319332 arthrogryposis multiplex 324262 cerebellar ataxia due to MGLUR1 congenita

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 14 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Autosomal recessive nail 4 Cases paraplegia type 35 280654 dysplasia 2 Autosomal recessive spastic Autosomal recessive 23 Cases 139480 Families 93329 paraplegia type 39 omodysplasia Autosomal recessive optic 17 Cases Autosomal recessive spastic 2 Cases 227976 320370 atrophy, OPA7 type paraplegia type 43 Autosomal recessive Autosomal recessive spastic 3 Cases 8 Cases 320401 1366 palmoplantar keratoderma and paraplegia type 44

congenital alopecia 7 Autosomal recessive spastic Autosomal recessive primary 320396 Families paraplegia type 45 immunodeficiency with defective 3 Cases 437552 spontaneous natural killer cell Autosomal recessive spastic 5 Cases 320391 cytotoxicity paraplegia type 46 Autosomal recessive severe 4 Cases Autosomal recessive spastic 2 Cases 420702 congenital neutropenia due to 306511 paraplegia type 48 CSF3R deficiency Autosomal recessive spastic 9 Cases Autosomal recessive severe 319199 2 Cases paraplegia type 53 420699 congenital neutropenia due to 6 Autosomal recessive spastic CXCR2 deficiency 320380 Families Autosomal recessive severe paraplegia type 54 57 Cases 331176 congenital neutropenia due to Autosomal recessive spastic 14 Cases 320375 G6PC3 deficiency paraplegia type 55 Autosomal recessive severe 5 14 Cases Autosomal recessive spastic 423384 congenital neutropenia due to 320411 Families paraplegia type 56 JAGN1 deficiency Autosomal recessive spastic 54 Cases Autosomal recessive spastic 2 Cases 314603 431329 ataxia with leukoencephalopathy paraplegia type 57 Autosomal recessive spastic 6 Cases Autosomal recessive spastic 3 Cases 254343 ataxia-optic atrophy-dysarthria 401795 paraplegia type 59 syndrome Autosomal recessive spastic 1 Case Autosomal recessive spastic 1 Family 401800 100995 paraplegia type 60 paraplegia type 14 Autosomal recessive spastic 4 Cases 10 401780 Autosomal recessive spastic paraplegia type 61 100996 Families Autosomal recessive spastic 7 Cases paraplegia type 15 401785 paraplegia type 62 Autosomal recessive spastic 9 Cases Autosomal recessive spastic 2 Cases 209951 401805 paraplegia type 18 paraplegia type 63 Autosomal recessive spastic 36 Cases Autosomal recessive spastic 4 Cases 101000 401810 paraplegia type 20 paraplegia type 64 Autosomal recessive spastic 35 Cases Autosomal recessive spastic 2 Cases 101001 401815 paraplegia type 21 paraplegia type 66 5 Autosomal recessive spastic Autosomal recessive spastic 2 Cases 101003 Families 401820 paraplegia type 23 paraplegia type 67

Autosomal recessive spastic 2 Cases Autosomal recessive spastic 1 Family 401830 101004 paraplegia type 69 paraplegia type 24 Autosomal recessive spastic 4 Cases Autosomal recessive spastic 1 Family 401835 101005 paraplegia type 70 paraplegia type 25 Autosomal recessive spastic 1 Case 10 401840 Autosomal recessive spastic paraplegia type 71 101006 Families paraplegia type 26 Autosomal recessive spastic 11 Cases 468661 paraplegia type 74 Autosomal recessive spastic 10 Cases 101007 Autosomal recessive spastic 5 Cases paraplegia type 27 459056 paraplegia type 75 Autosomal recessive spastic 7 Cases 101008 7 paraplegia type 28 Autosomal recessive spastic 488594 Families Autosomal recessive spastic 1 Family paraplegia type 76 171622 paraplegia type 32 466722 Autosomal recessive spastic 8 Cases 171629 Autosomal recessive spastic 38 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 15 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families paraplegia type 77 Autosomal recessive spastic 7 Cases 5 Cases 513436 85284 BRESEK syndrome paraplegia type 78 2 BVES-related limb-girdle 3 Cases Autosomal recessive spastic 476084 447760 Families muscular dystrophy paraplegia type 9B Bacterial susceptibility due to 24 Cases 183713 Autosomal recessive 3 TLR signaling pathway deficiency

95433 spinocerebellar ataxia-blindness- Families 3.0 P 36234 Bacterial toxic-shock syndrome deafness syndrome Autosomal recessive 4 Cases 40 Cases 401979 spondylometaphyseal dysplasia, 1225 Baller-Gerold syndrome

Mégarbané type 8 Cases Autosomal semi-dominant 1226 Bamforth-Lazarus syndrome 7 Cases 280365 severe lipodystrophic 2 Cases 1227 Bangstad syndrome laminopathy 3 Autosomal spastic paraplegia 1 Family 101010 Families 1228 Banki syndrome type 30 Baraitser-Winter 60 Cases Autosomal spastic paraplegia 19 Cases 2995 397946 cerebrofrontofacial syndrome type 58 16 Cases Autosomal spastic paraplegia 14 Cases 1231 Barber-Say syndrome 401849 type 72 0.7 P* 7 110 Bardet-Biedl syndrome Autosomal systemic lupus 300345 Families 0.5 BP* erythematosus 110 Bardet-Biedl syndrome

826 0.22 P* 454836 Avian influenza Cases 111 Barth syndrome

24 Cases 0.5 P* 1234 Bartsocas-Papas syndrome 782 Axenfeld-Rieger syndrome

0.1 I* Axial spondylometaphyseal 13 Cases 112 Bartter syndrome 168549 dysplasia Basel-Vanagaite-Smirin-Yosef 7 Cases 18 Cases 464738 1272 Aymé-Gripp syndrome syndrome

20 Cases B-cell chronic lymphocytic 48.0 P* 100976 Bathing suit ichthyosis 67038 leukemia 145 B-cell immunodeficiency-limb 10 Cases 166113 Bazex syndrome Cases 567502 anomaly-urogenital

malformation syndrome 143

17.45 I* 113 Bazex-Dupré-Christol syndrome Cases 171915 B-cell non-Hodgkin lymphoma

0.05 I* 2.0 P* 86852 B-cell prolymphocytic leukemia 98895 Becker muscular dystrophy

B3GALT6-related 15 1.53 P 536467 spondylodysplastic Ehlers-Danlos Families 98895 Becker muscular dystrophy

syndrome 2.2 BP* 1 Case 98895 Becker muscular dystrophy 79332 B4GALT1-CDG

3.5 BP* B4GALT7-related 116 Beckwith-Wiedemann syndrome 6 Cases 75496 spondylodysplastic Ehlers-Danlos 2 Cases syndrome 1237 Beemer-Ertbruggen syndrome

8 Cases 464336 BENTA disease 2

1241 Bencze syndrome Families BICD2-related autosomal 60 Cases 363454 dominant childhood-onset Benign Samaritan congenital 4 Cases proximal spinal muscular atrophy 324581 myopathy 9 217266 BNAR syndrome 251287 Benign concentric annular 27 Cases Families

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 16 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families macular dystrophy 100 33 Cases 123 Björnstad syndrome 1949 Benign familial neonatal epilepsy Families

0.67 BP* 124 Blackfan-Diamond anemia 10 Benign familial neonatal-infantile 140927 Families 3.05 BP seizures 93930 Bladder exstrophy

Benign infantile focal epilepsy 36 Cases Bleeding diathesis due to a 20 Cases 166308 with midline spikes and waves 73271 collagen receptor defect during sleep Bleeding disorder due to CalDAG- 3 Cases Benign infantile seizures 100 420566 GEFI deficiency 166305 associated with mild Cases Bleeding disorder due to P2Y12 14 Cases 36355 gastroenteritis defect Benign nocturnal alternating 12 Cases Blepharo-cheilo-odontic 50 Cases 209973 1997 hemiplegia of childhood syndrome Benign paroxysmal tonic upgaze 12 Cases 3 1179 Blepharonasofacial malformation of childhood with ataxia 1252 Families 150 syndrome Benign paroxysmal torticollis of 71518 Cases Blepharophimosis-intellectual 58 Cases infancy 293642 disability syndrome 6.0 P* Blepharophimosis-intellectual 30 Cases 252164 Benign schwannoma 2728 disability syndrome, Ohdo type 100 Blepharophimosis-intellectual 20 Cases 274 Bernard-Soulier syndrome Cases 3047 disability syndrome, SBBYS type Blepharophimosis-ptosis- 6 Cases 0.14 BP* 2057 esotropia-syndactyly-short 118 Beta-mannosidosis stature syndrome Beta-mercaptolactate cysteine 1 Case Blepharoptosis-myopia-ectopia 3 Cases 1035 1259 disulfiduria lentis syndrome Beta-propeller protein- 68 Cases Blindness-scoliosis- 4 Cases 329284 171844 associated neurodegeneration arachnodactyly syndrome Beta-sarcoglycan-related limb- 0.1 P* Blomstrand lethal 13 Cases 119 50945 girdle muscular dystrophy R4 chondrodysplasia 1.0 I 300 848 Beta-thalassemia 125 Bloom syndrome Cases 10.0 I* 848 Beta-thalassemia 1.0 BP Beta-ureidopropionase 5 Cases 16 Blue cone monochromatism 65287 deficiency 1.0 P Bilateral acute depigmentation 62 Cases 16 Blue cone monochromatism 69736 of the iris 200 3 Bilateral microtia-deafness-cleft 1059 Blue rubber bleb nevus Cases 140963 Families palate syndrome 40 Cases 200 217008 Bockenheimer syndrome Bilateral striopallidodentate 1980 Cases Body skin hyperlaxity due to calcinosis 11 Cases 91135 vitamin K-dependent coagulation 0.002 I* 424982 Biliary cystadenocarcinoma factor deficiency 46 Cases 1.6 BP 97297 Bohring-Opitz syndrome 79241 Biotinidase deficiency Bone dysplasia, lethal Holmgren 7 Cases 1.6 P* 1842 79241 Biotinidase deficiency type 0.8 I* 23 Cases 223727 Bone sarcoma 364198 Bipartite talus 9.29 P* 0.35 P 223727 Bone sarcoma 179 Birdshot chorioretinopathy 1261 Bonnemann-Meinecke-Reich 4 Cases 122 Birt-Hogg-Dubé syndrome 0.5 P*

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 17 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families syndrome Brain malformation-congenital 2 Cases 10 Cases 75389 heart disease-postaxial 1263 Boomerang dysplasia polydactyly syndrome Borjeson-Forssman-Lehmann 50 Cases Brain malformations- 127 musculoskeletal abnormalities- 29 Cases syndrome 500150 16 Cases facial dysmorphism-intellectual 69737 Bosley-Salih-Alorainy syndrome disability syndrome 100 0.022 I* 1267 Botulism 209905 Brain-lung-thyroid syndrome Cases

60 Cases 1270 Bowen-Conradi syndrome 150

7 Cases 1297 Branchio-oculo-facial syndrome Cases 93382 Brachydactyly type A6

1 Family Branchiogenic deafness 5 Cases 93397 Brachydactyly type A7 50815 syndrome 10 Branchioskeletogenital 7 Cases Brachydactyly-arterial 1299 1276 Families syndrome hypertension syndrome 65 Cases 90354 Brittle cornea syndrome 4 Brachydactyly-elbow wrist 1275 Families 13.0 P* dysplasia syndrome 70589 Bronchopulmonary dysplasia

100 Brachydactyly-long thumb 4 Cases 2946 79493 Brooke-Spiegler syndrome Cases syndrome Brachydactyly-mesomelia- 2 Cases 1277 intellectual disability-heart 0.09 I* 1304 Brucellosis defects syndrome Brachydactyly-nystagmus- 1 Family 60 Cases 1246 2771 Bruck syndrome cerebellar ataxia syndrome Brachydactyly-preaxial hallux 8 Cases 20.0 P* 1278 130 Brugada syndrome varus syndrome Brachydactyly-short stature- 12 Cases 1.5 P* 166035 131 Budd-Chiari syndrome retinitis pigmentosa syndrome 2 1.1 P Brachydactyly-syndactyly, Zhao 131 Budd-Chiari syndrome 93409 Families type 0.1 I 131 Budd-Chiari syndrome Brachymorphism- 9 Cases 1292 onychodysplasia-dysphalangism 16.0 P 36258 Buerger disease syndrome 100 10.0 P* 36258 Buerger disease 1293 Brachyolmia Cases

Bullous diffuse cutaneous 40 Cases 280785 4 mastocytosis

93302 Brachyolmia, Maroteaux type Families 25.0 P* 703 Bullous pemphigoid

Brachytelephalangy- 0.17 I* 2 Cases 543 Burkitt lymphoma 1295 dysmorphism-Kallmann

syndrome 11

2 Cases 1200 Burn-McKeown syndrome Families 52047 Braddock syndrome

5 Cases 5.0 I 75374 Bradyopsia 1306 Buschke-Ollendorff syndrome

8 Cases 26 Cases 178506 Brain calcification, Rajab type 1262 Böök syndrome

Brain demyelination due to 0.11 P* 2 Cases 1308 C syndrome 168598 methionine adenosyltransferase

deficiency C11ORF73-related autosomal 6 Cases Brain dopamine-serotonin 8 Cases 495844 recessive hypomyelinating 352649 vesicular transport disease leukodystrophy

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 18 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families C12ORF65-related combined 30 Cases 150 497623 oxidative phosphorylation defect 140944 CLOVES syndrome Cases

0.15 I* 329918 C3 glomerulopathy COASY protein-associated 2 Cases 397725 12.0 P* neurodegeneration 329918 C3 glomerulopathy 12 Cases 1458 CODAS syndrome 148

135 CACH syndrome Cases 20 Cases 1466 COFS syndrome

1 Case 3 Cases 448010 CAD-CDG 263508 COG1-CDG

4 Cases 1 Case 369942 CADDS 435934 COG2-CDG

5 Cases 2 Cases 83472 CAMOS syndrome 263501 COG4-CDG

100 9 Cases 263487 COG5-CDG 71279 CANOMAD syndrome Cases

10 Cases 464443 COG6-CGD 8 Cases 468684 CCDC115-CDG 8 Cases 79333 COG7-CDG CD4+/CD56+ hematodermic 12.0 P* 86870 neoplasm 2 Cases 95428 COG8-CDG CEBPE-associated autoinflammation- 4 Cases CTCF-related 5 Cases 566067 363611 immunodeficiency-neutrophil neurodevelopmental disorder dysfunction syndrome 100

13 Cases 1310 Caffey disease Cases 66631 CEDNIK syndrome

CELSR1-related late-onset 11 Cases 5.0 P* 569816 280062 Calciphylaxis primary lymphedema 6.5 BP Calpain-3-related limb-girdle 1.0 P* 138 CHARGE syndrome 267 muscular dystrophy R1 9.0 P* Calpain-3-related limb-girdle 47 Cases 138 CHARGE syndrome 565909 muscular dystrophy D4 60 Cases Calvarial doughnut lesions-bone 20 Cases 139 CHILD syndrome 85192 fragility syndrome 8 Cases 8 Cases 3474 CHIME syndrome 1318 Campomelia, Cumming type

2 0.33 BP* 263463 CHST3-related skeletal dysplasia Families 140 Campomelic dysplasia

1 Family CIDEC-related familial partial 1 Case 1319 Camptobrachydactyly 435651 lipodystrophy Camptodactyly syndrome, 8 Cases 24 Cases 1327 251383 CK syndrome Guadalajara type 1 Camptodactyly syndrome, 2 Cases 6 Cases 1326 168984 CLAPO syndrome Guadalajara type 2 Camptodactyly syndrome, 5 Cases CLCN4-related X-linked 38 Cases 488434 485350 Guadalajara type 3 intellectual disability syndrome 30 Camptodactyly-arthropathy- 50 Cases 2848 Families 284448 CLIPPERS coxa-vara-pericarditis syndrome

2 Cases Camptodactyly-fibrous tissue 314629 CLN11 disease 3 Cases 1321 hyperplasia-skeletal dysplasia

4 Cases syndrome 352709 CLN13 disease Camptodactyly-joint 4 Cases 2 Cases 1323 contractures-facial skeletal 228357 CLN9 disease defects syndrome

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 19 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Camptodactyly-tall stature- 30 Cases 150 85164 scoliosis-hearing loss syndrome 139411 Carney triad Cases

Camptodactyly-taurinuria 17 Cases 1325 syndrome 20

300 97286 Carney-Stratakis syndrome Families

1328 Camurati-Engelmann disease Cases

Carnitine palmitoyl transferase 60 Cases 156 1.0 BP 1A deficiency 141 Canavan disease 300 Carnitine palmitoyl transferase II 21 Cases 228302 Cases 171881 Cap myopathy deficiency, myopathic form

20 67 Cases Carnitine palmitoyl transferase II 160148 Cap polyposis 228308 Families deficiency, neonatal form 261 Capillary malformation- 30 137667 Cases Carnitine palmitoyl transferase II arteriovenous malformation 228305 Families deficiency, severe infantile form 7.0 I 70482 Carcinoma of esophagus 300 Carnitine palmitoyltransferase II 6.67 I* 157 Cases 70482 Carcinoma of esophagus deficiency

9.8 P Carnitine palmitoyltransferase II 1.0 P* 70482 Carcinoma of esophagus 157 deficiency 7.1 P* Carnitine-acylcarnitine 60 Cases 70482 Carcinoma of esophagus 159 translocase deficiency 12.2 24 Cases 70482 Carcinoma of esophagus 1361 Carnosinase deficiency

Carcinoma of esophagus, salivary 0.004 I* 0.2 BP 418945 1361 Carnosinase deficiency gland type Carcinoma of gallbladder and 12.0 I 0.1 I 56044 53035 Caroli disease extrahepatic biliary tract Carcinoma of gallbladder and 4.37 I* 70 Cases 56044 65759 Carpenter syndrome extrahepatic biliary tract Cardiac anomalies-heterotaxy 9 Cases 6 Cases 137628 93973 Carpenter-Waziri syndrome syndrome Cardiac-valvular Ehlers-Danlos 6 Cases 7 Cases 230851 65282 Carvajal syndrome syndrome Cardiocranial syndrome, Pfeiffer 7 Cases 1.35 BP* 2872 195 Cat-eye syndrome type 300 6.6 P* 50839 Cat-scratch disease 1340 Cardiofaciocutaneous syndrome Cases Cataract-aberrant oral frenula- 3 Cases 1373 40.0 P* growth delay syndrome 97292 Cardiogenic shock Cataract-ataxia-deafness 2 Cases 1368 Cardiomyopathy-cataract-hip 9 Cases syndrome 1345 Cataract-congenital heart spine disease syndrome 2 Cases Cardiomyopathy-hypotonia- 2 Cases 314993 disease-neural tube defect 91130 lactic acidosis syndrome syndrome Cardiospondylocarpofacial 5 Cases Cataract-deafness-hypogonadism 3 Cases 3238 1383 syndrome syndrome 3 20 Cases 1358 Carey-Fineman-Ziter syndrome 162 Cataract-glaucoma syndrome Families

160

1359 Carney complex Cases Cataract-growth hormone deficiency-sensory neuropathy- 3 Cases 436174 3 sensorineural hearing loss- Carney complex-trismus- 319340 Families skeletal dysplasia syndrome pseudocamptodactyly syndrome Cataract-intellectual disability- 3 Cases 1381 anal atresia-urinary defects

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 20 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families syndrome Cataract-intellectual disability- 20 Cases 21 Cases 1387 66625 Cerebrooculonasal syndrome hypogonadism syndrome 8 5 Cases 169079 Cernunnos-XLF deficiency 1377 Cataract-microcornea syndrome Families

Cervical hypertrichosis- 4 Cases 2218 Cataract-nephropathy- 2 Cases peripheral neuropathy syndrome 1380 encephalopathy syndrome Channelopathy-associated 20 Cases 88642 Catecholaminergic polymorphic 10.0 P* congenital insensitivity to pain 3286 ventricular tachycardia 109

33 Cases 46627 Char syndrome Cases 1388 Catel-Manzke syndrome

Caudal appendage-deafness 2 Cases Charcot-Marie-Tooth disease 17.5 P 1123 65753 syndrome type 1 170 Charcot-Marie-Tooth disease 1 Family Celiac disease-epilepsy-cerebral 101101 1459 Cases type 2B2 calcification syndrome Charcot-Marie-Tooth disease 4 Cases 228374 30 Cases type 2B5 3258 Cenani-Lenz syndrome Charcot-Marie-Tooth disease 13 Cases 101102 Central cloudy dystrophy of 24 Cases type 2H 98972 François Charcot-Marie-Tooth disease 18 Cases 300319 4.0 P* type 2P 178029 Central diabetes insipidus Charcot-Marie-Tooth disease 1 Case 397968 Central nervous system type 2R 2 Cases 3240 calcification-deafness-tubular Charcot-Marie-Tooth disease 35 Cases 443073 acidosis-anemia syndrome type 2S Central nervous system 0.07 I* Charcot-Marie-Tooth disease 10 Cases 251870 495274 embryonal tumor type 2T 500 11 Charcot-Marie-Tooth disease 73256 Central neurocytoma Cases 99955 Families type 4B1

28.0 P* Charcot-Marie-Tooth disease 3 Cases 411527 Central retinal vein occlusion 363981 type 4B3 Centripetalis recessive 10 Cases Charcot-Marie-Tooth disease 15 Cases 89841 99954 dystrophic epidermolysis bullosa type 4H Cerebellar ataxia with 100 Charcot-Marie-Tooth disease 18 Cases 504476 neuropathy and bilateral Cases 139515 type 4J vestibular areflexia syndrome Charcot-Marie-Tooth disease- 7 Cases Cerebellar ataxia-areflexia-pes 90103 deafness-intellectual disability cavus-optic atrophy- 10 Cases 1171 syndrome sensorineural hearing loss Charcot-Marie-Tooth 25.0 P* syndrome 166 disease/Hereditary motor and Cerebellar hypoplasia- 3 Cases sensory neuropathy 2246 tapetoretinal degeneration 4 Cases 1406 Charlie M syndrome syndrome 3 100 Cerebellar-facial-dental 444072 Families 1221 Cheilitis glandularis Cases syndrome

Cerebral arteriovenous 6.0 P* 300 46724 malformation 184 Cherubism Cases Cerebral autosomal dominant 3.0 P* 136 arteriopathy-subcortical infarcts- 0.12 I* 324625 Chikungunya leukoencephalopathy Cerebrocostomandibular 75 Cases 70 Cases 1393 90280 Chilblain lupus syndrome 9 Cases 22 Cases 314679 Cerebrofacioarticular syndrome 209908 Childhood apraxia of speech

1394 Cerebrofaciothoracic dysplasia 20 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 21 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 2.0 P* 168782 Childhood disintegrative disorder Chromophobe renal cell 0.01 I* 319303 Childhood encephalopathy due carcinoma 5 Cases 293955 to thiamine pyrophosphokinase Chronic atrial and intestinal 17 Cases 435988 deficiency dysrhythmia syndrome Childhood-onset autosomal 22 Cases Chronic diarrhea with villous 2 Cases 363677 recessive myopathy with 1670 atrophy external ophthalmoplegia Chronic enteropathy associated 18 Cases Childhood-onset basal ganglia 4 Cases 468641 497906 with SLCO2A1 gene degeneration syndrome 0.46 BP Childhood-onset benign chorea 3 Cases 379 Chronic granulomatous disease 494541 with striatal involvement 0.5 BP* 379 Chronic granulomatous disease Childhood-onset motor and cognitive regression syndrome 7 Cases 1.0 P* 500180 396 Chronic hiccup with extrapyramidal movement disorder Chronic infantile diarrhea due to 32 Cases Childhood-onset progressive 314373 3 guanylate cyclase 2C overactivity contractures-limb-girdle 466921 Families Chronic inflammatory 3.7 P* weakness-muscle dystrophy 2932 demyelinating polyneuropathy syndrome 1.25 I* Childhood-onset spasticity with 3 Cases 521 Chronic myeloid leukemia 401866 hyperglycinemia 5.63 8.6 BP* 521 Chronic myeloid leukemia 137914 Choanal atresia

6.0 P* 4.2 I 521 Chronic myeloid leukemia 70567 Cholangiocarcinoma

Chronic myelomonocytic 0.29 I* 4.0 I* 98823 70567 Cholangiocarcinoma leukemia

Chronic myeloproliferative 0.53 I* 2.1 P 86830 70567 Cholangiocarcinoma disease, unclassifiable

Chronic nonbacterial 0.3 P Cholestasis-lymphedema 47 Cases 324964 osteomyelitis/Chronic recurrent 1414 syndrome multifocal osteomyelitis Cholestasis-pigmentary Chronic nonbacterial 5 Cases 2.5 I 1415 retinopathy-cleft palate 324964 osteomyelitis/Chronic recurrent

syndrome multifocal osteomyelitis Chondrodysplasia punctata, 3 Cases Chronic primary adrenal 0.4 I* 79347 101959 Toriello type insufficiency Chondrodysplasia with joint 4 Cases Chronic primary adrenal 14.0 P* 280586 101959 dislocations, gPAPP type insufficiency Chondrodysplasia-disorder of sex 2 Cases Chronic thromboembolic 3.0 P* 1422 70591 development syndrome pulmonary hypertension Chondroectodermal dysplasia 4 Cases 3 Cases 319195 93971 Chudley-Lowry-Hoar syndrome with night blindness 50 Cases 25 Cases 404507 Chondromyxoid fibroma 314597 Chudley-McCullough syndrome

0.24 I* 55 Cases 55880 Chondrosarcoma 71 Chylomicron retention disease

3.55 500 55880 Chondrosarcoma 167 Chédiak-Higashi syndrome Cases 0.01 I* 251899 Choroid plexus carcinoma Circumscribed palmoplantar 17 Cases 0.35 69744 251899 Choroid plexus carcinoma hypokeratosis Cirrhosis-dystonia-polycythemia- 20 Cases Choroidal atrophy-alopecia 2 Cases 309854 1433 hypermanganesemia syndrome syndrome 2.4 P* 2.0 P* 247525 Citrullinemia type I 180 Choroideremia 391 Classic Hodgkin lymphoma 2.463 I* 85278 Christianson syndrome 30 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 22 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 80.0 BP 199306 Cleft lip/palate 22.9 391 Classic Hodgkin lymphoma Cleft lip/palate-deafness-sacral 2 Cases 2003 Classic Hodgkin lymphoma, 0.04 I* lipoma syndrome 98846 lymphocyte-depleted type Cleft lip/palate-ectodermal 50 Cases 3253 Classic Hodgkin lymphoma, 0.1 I* dysplasia syndrome 98845 lymphocyte-rich type Cleft lip/palate-intestinal 5 Cases Classic Hodgkin lymphoma, 0.42 I* 2001 malrotation-cardiopathy 98844 mixed cellularity type syndrome Classic Hodgkin lymphoma, 1.28 I* 53.6 BP* 98843 2014 Cleft palate nodular sclerosis type Classic congenital adrenal Cleft palate-large ears-small 8 Cases 7.0 P* 2013 90794 hyperplasia due to 21- head syndrome

hydroxylase deficiency Cleft palate-lateral synechia 11 Cases 2016 Classic congenital adrenal syndrome 7.0 BP 90794 hyperplasia due to 21- Cleft palate-short stature- 2 Cases 2015 hydroxylase deficiency vertebral anomalies syndrome Classic congenital adrenal Cleft palate-stapes fixation- 2 Cases 2010 hyperplasia due to 21- 7.5 BP* oligodontia syndrome 315306 hydroxylase deficiency, salt 0.1 P 1452 Cleidocranial dysplasia wasting form Classic congenital adrenal 0.4 BP* hyperplasia due to 21- 7.5 P* 1452 Cleidocranial dysplasia 315306 hydroxylase deficiency, salt 2 Cases 1453 Cleidorhizomelic syndrome wasting form Classic congenital adrenal 0.75 BP* hyperplasia due to 21- 2.5 P* 93929 Cloacal exstrophy 315311 hydroxylase deficiency, simple 0.54 BP 93929 Cloacal exstrophy virilizing form 2.1 I* Cloverleaf skull-multiple 3 Cases 79239 Classic galactosemia 93267 congenital anomalies syndrome 0.29 I* 1.0 BP* 58017 Classic hairy cell leukemia 51577 Cobblestone lissencephaly

3.12 Cobblestone lissencephaly 58017 Classic hairy cell leukemia 6 Cases 352682 without muscular or ocular 0.3 BP 394 Classic homocystinuria involvement 1.0 P* 1.65 P* 90068 Cocaine intoxication 394 Classic homocystinuria 2 Cochleosaccular degeneration- 0.5 I* 3233 Families 2584 Classic mycosis fungoides cataract syndrome

Classic neuroendocrine tumor of 0.25 I 0.5 I* 329977 191 Cockayne syndrome appendix 5.0 P 0.2 BP* 287 Classical Ehlers-Danlos syndrome 191 Cockayne syndrome

Classical-like Ehlers-Danlos 17 Cases 1.5 P 230839 192 Coffin-Lowry syndrome syndrome type 1 Classical-like Ehlers-Danlos 7 Cases 1.5 P* 536532 192 Coffin-Lowry syndrome syndrome type 2 Clear cell adenocarcinoma of the 0.32 I* 190 398971 ovary 1465 Coffin-Siris syndrome Cases 1.99 I* 319276 Clear cell renal carcinoma 300 Cleft lip and palate-craniofacial 7 Cases 1467 Cogan syndrome Cases 508476 dysmorphism-congenital heart

defect-hearing loss syndrome Cognitive impairment-coarse 11 Cases 2 Cases 444077 facies-heart defects-obesity- 1995 Cleft lip-retinopathy syndrome pulmonary involvement-short

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 23 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families stature-skeletal dysplasia Combined immunodeficiency 9 Cases 231154 syndrome due to partial RAG1 deficiency 200 Combined immunodeficiency 2 Cases 193 Cohen syndrome Cases 221139 with faciooculoskeletal

anomalies 0.1 P* Combined oxidative 32 Cases 31824 Colchicine poisoning 324535 phosphorylation defect type 11 6 Cases Combined oxidative 2 Cases 157820 Cold-induced sweating syndrome 319514 phosphorylation defect type 13 3 Cases Combined oxidative 5 Cases 2050 Cole-Carpenter syndrome 319519 phosphorylation defect type 14 Coloboma of macula- 10 Cases Combined oxidative 16 Cases 1471 319524 brachydactyly type B syndrome phosphorylation defect type 15 Colobomatous macrophthalmia- 21 Cases 20 468672 Combined oxidative microcornea syndrome 369913 Families phosphorylation defect type 17 5 Colobomatous microphthalmia- 424099 Families Combined oxidative 1 Case rhizomelic dysplasia syndrome 254920 phosphorylation defect type 2 Colobomatous optic disc-macular Combined oxidative 2 Cases 3 Cases 420728 435930 atrophy-chorioretinopathy phosphorylation defect type 20

syndrome Combined oxidative 2 Cases 420733 5.0 BP phosphorylation defect type 21 1198 Colonic atresia Combined oxidative 11 Cases 444013 Combined deficiency of factor V 0.5 P* phosphorylation defect type 23 35909 and factor VIII Combined oxidative 3 Cases 444458 Combined hamartoma of the 120 phosphorylation defect type 24

440727 retina and retinal pigment Cases Combined oxidative 2 Cases 447954 epithelium phosphorylation defect type 25 Combined immunodeficiency 18 Cases Combined oxidative 2 Cases 238505 477684 due to CD27 deficiency phosphorylation defect type 26 Combined immunodeficiency 6 Cases Combined oxidative 3 Cases 538958 477774 due to CD70 deficiency phosphorylation defect type 27 Combined immunodeficiency 10 Cases Combined oxidative 1 Case 169090 478029 due to CRAC channel dysfunction phosphorylation defect type 29 Combined immunodeficiency 11 Cases Combined oxidative 2 Cases 217390 478042 due to DOCK8 deficiency phosphorylation defect type 30 Combined immunodeficiency 5 Cases Combined oxidative 6 Cases 505227 565624 due to GINS1 deficiency phosphorylation defect type 39 Combined immunodeficiency 6 Cases Combined oxidative 2 Cases 357329 254925 due to IL21R deficiency phosphorylation defect type 4 Combined immunodeficiency 13 Cases Combined oxidative 7 Cases 538963 254930 due to ITK deficiency phosphorylation defect type 7 Combined immunodeficiency 23 Cases Combined oxidative 7 Cases 445018 319504 due to LRBA deficiency phosphorylation defect type 8 Combined immunodeficiency 3 Cases Combined oxidative 4 Cases 397964 319509 due to MALT1 deficiency phosphorylation defect type 9 Combined immunodeficiency 7 Cases Combined pancreatic lipase- 3 Cases 504530 309111 due to Moesin deficiency colipase deficiency Combined immunodeficiency 6 Cases Complement component 3 27 Cases 317428 280133 due to ORAI1 deficiency deficiency Combined immunodeficiency 1 Case Complete androgen insensitivity 3.0 I* 431149 99429 due to OX40 deficiency syndrome Combined immunodeficiency 7 Cases Complete androgen insensitivity 0.83 P 314689 99429 due to STK4 deficiency syndrome 2 Combined immunodeficiency Complete atrioventricular septal 20.0 BP* 476113 Families 1329 due to TFRC deficiency defect 98949 Complete cryptophthalmia 15 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 24 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Complex lethal 6 Cases 50 Cases 457378 86816 Congenital analbuminemia osteochondrodysplasia Complication after organ 9.0 P* 16 Cases 306644 1195 Congenital atransferrinemia transplantation 13.0 I* Congenital autosomal recessive 5 Cases 268316 Complication in hemodialysis 566192 small-platelet thrombocytopenia Complications after Congenital axonal neuropathy 7 Cases 0.65 P* 538101 90053 hematopoietic stem cell with encephalopathy

transplantation Congenital bilateral absence of 50.0 P* 48 Composite 39 Cases vas deferens 458758 hemangioendothelioma Congenital bile acid synthesis 2 Cases 79302 0.01 I* defect type 3 168966 Composite lymphoma Congenital bile acid synthesis 5 Cases 79095 Conductive deafness-malformed 8 Cases defect type 4 3216 external ear syndrome Congenital brachyesophagus- 8 Cases Conductive deafness-ptosis- 3 Cases 514352 intrathoracic stomach-vertebral 3236 skeletal anomalies syndrome anomalies syndrome Cone dystrophy with 45 Cases Congenital brain dysgenesis due 209932 3 Cases supernormal rod response 71278 to glutamine synthetase

2.5 P* deficiency 1872 Cone rod dystrophy Congenital cataract-hearing loss- 5 Cases 2 Cases 300313 severe developmental delay 221142 Confetti-like macular atrophy syndrome Congenital cataract-hypertrophic Congenital absence of upper arm 0.62 BP 40 Cases 294975 1369 cardiomyopathy-mitochondrial and forearm with hand present Congenital absence/hypoplasia 2 myopathy syndrome Congenital cataract-progressive 973 of fingers excluding thumb, Families 3 Cases 330054 muscular hypotonia-hearing loss- unilateral 13.35 I* developmental delay syndrome 418 Congenital adrenal hyperplasia Congenital cataract-severe 2 Cases 6.7 BP* 521432 neonatal hepatopathy-global 418 Congenital adrenal hyperplasia developmental delay syndrome Congenital cataracts-facial 170 10.0 P* 418 Congenital adrenal hyperplasia 48431 dysmorphism-neuropathy Cases

Congenital adrenal hyperplasia syndrome 0.75 BP* 90795 due to 11-beta-hydroxylase Congenital cerebellar ataxia due 6 Cases 512260 deficiency to RNU12 mutation Congenital adrenal hyperplasia Congenital chronic diarrhea with 2 Cases 0.47 P* 329242 90795 due to 11-beta-hydroxylase protein-losing enteropathy Congenital deficiency in alpha- 22 Cases deficiency 168612 Congenital adrenal hyperplasia fetoprotein 0.1 P* 90793 due to 17-alpha-hydroxylase 30.0 BP 2140 Congenital diaphragmatic hernia deficiency Congenital adrenal hyperplasia 21.2 BP* 68 Cases 2140 Congenital diaphragmatic hernia 90791 due to 3-beta-hydroxysteroid

dehydrogenase deficiency Congenital disorder of 1.5 BP* 137 Congenital adrenal hyperplasia glycosylation 0.75 BP* 95699 due to cytochrome P450 Congenital dyserythropoietic 0.16 BP* 85 oxidoreductase deficiency anemia Congenital agenesis of the 6 Cases 740 495879 Congenital dyserythropoietic scrotum 85 Cases anemia Congenital alpha2-antiplasmin 40 Cases 79 deficiency Congenital dyserythropoietic 60 Cases 98870 Congenital alveolar capillary 40 Cases anemia type III 210122 dysplasia Congenital dyserythropoietic 4 Cases 293825 Congenital amegakaryocytic 100 anemia type IV 3319 thrombocytopenia Cases 103910 Congenital enterocyte heparan 3 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 25 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families sulfate deficiency Congenital insensitivity to pain 3 Cases 453510 Congenital erosive and vesicular 31 Cases with severe intellectual disability 231573 dermatosis Congenital intrauterine infection- 30 Cases 1229 200 like syndrome Congenital erythropoietic 79277 Cases 100 porphyria Congenital intrinsic factor 332 Cases deficiency Congenital erythropoietic 0.065 I* 79277 porphyria Congenital isolated 2.0 BP 657 0.05 P* hyperinsulinism 325 Congenital factor II deficiency Congenital labioscrotal agenesis- 0.1 P* cerebellar malformation-corneal 3 Cases 326 Congenital factor V deficiency 495875 dystrophy-facial dysmorphism 0.33 P* syndrome 327 Congenital factor VII deficiency 17 Cases 1954 Congenital lethal erythroderma 0.1 P* 329 Congenital factor XI deficiency Congenital lethal myopathy, 4 Cases 210163 0.04 I* Compton-North type 331 Congenital factor XIII deficiency Congenital limbs-face 14 Cases 0.05 P* 562528 contractures-hypotonia- 331 Congenital factor XIII deficiency developmental delay syndrome 0.15 P* 4.0 BP 335 Congenital fibrinogen deficiency 1928 Congenital lobar emphysema

Congenital generalized 25 Cases 2 Cases 93109 Congenital megacalycosis 476406 hypercontractile muscle stiffness

syndrome Congenital membranous Congenital generalized 40 Cases nephropathy due to 15 Cases 1023 69063 hypertrichosis, Ambras type fetomaternal anti-neutral Congenital generalized 0.5 P* endopeptidase alloimmunization 528 Congenital microcephaly-severe lipodystrophy 20 Cases 2.2 BP* 391376 encephalopathy-progressive 98976 Congenital glaucoma cerebral atrophy syndrome Congenital multiple café-au-lait 4.54 BP 2 Cases 60041 Congenital heart block 508512 macules-increased sister

chromatid exchange syndrome Congenital heart defect-round 3 Cases 1355 face-developmental delay Congenital muscular dystrophy 23 Cases 157973 syndrome due to LMNA mutation Congenital hereditary 68 Cases Congenital muscular dystrophy 6 Cases 98975 98893 endothelial dystrophy type I type 1B Congenital hereditary facial Congenital muscular dystrophy 14 Cases 13 Cases 371007 306530 paralysis-variable hearing loss with hyperlaxity Congenital muscular dystrophy 0.03 P* syndrome 34520 46.5 BP* with integrin alpha-7 deficiency 2185 Congenital hydrocephalus Congenital muscular dystrophy 3 Cases 38.0 BP* 329178 with intellectual disability and 442 Congenital hypothyroidism severe epilepsy Congenital muscular dystrophy- Congenital hypothyroidism due 21.3 P* 7 Cases 95711 1875 infantile cataract-hypogonadism to developmental anomaly syndrome Congenital hypothyroidism due 1.0 P* 95715 to transplacental passage of TSH- Congenital muscular dystrophy- respiratory failure-skin 4 Cases binding inhibitory antibodies 486815 abnormalities-joint hyperlaxity Congenital ichthyosis-intellectual 2 Cases syndrome 352333 disability-spastic quadriplegia 0.3 P* syndrome 590 Congenital myasthenic syndrome

Congenital ichthyosis- 2 Cases 2271 microcephalus-tetraplegia Congenital myopathy with 5 Cases 319160 syndrome internal nuclei and atypical cores Congenital insensitivity to pain 2 Cases Congenital myopathy with 2 Cases 217399 424107 with hyperhidrosis myasthenic-like onset

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 26 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Congenital myopathy with 2 Cases Congenital sucrase-isomaltase 20.0 P* 544602 35122 reduced type 2 muscle fibers deficiency Congenital myopathy, Paradas 2 Cases 1.3 BP* 199329 499009 Congenital syphilis type 1.0 P Congenital total pulmonary 9.0 BP 206973 Congenital myotonia 99125 venous return anomaly Congenital neuronal ceroid 10 Cases 33.0 BP* 168486 858 Congenital toxoplasmosis lipofuscinosis Congenital neutropenia- 0.5 BP* 16 Cases 92050 Congenital tufting enteropathy 369852 myelofibrosis-nephromegaly

syndrome 130

Congenital non-bullous 0.3 P* 291 Congenital varicella syndrome Cases 79394 ichthyosiform erythroderma Congenital osteogenesis Congenital vertebral-cardiac- 4 Cases 3 Cases 521438 2772 imperfecta-microcephaly- renal anomalies syndrome

cataracts syndrome Congenitally corrected 3.0 BP 10 Cases 216694 transposition of the great 313906 Congenital pancreatic cyst arteries 3 Cases Congenitally short costocoracoid 1 Family 139414 Congenital panfollicular nevus 2391 ligament Congenital primary lymphedema 23 Cases Congenitally uncorrected 569821 24.25 BP* of Gordon 860 transposition of the great

Congenital progressive bone arteries marrow failure-B-cell 5 Cases Connective tissue disorder due to 2 Cases 508542 300284 immunodeficiency-skeletal lysyl hydroxylase-3 deficiency dysplasia syndrome 3 Cases 420794 Cono-spondylar dysplasia 200 Congenital pseudoarthrosis of 66630 Cases Constitutional megaloblastic the clavicle 6 Cases 319651 anemia with severe neurologic

Congenital pulmonary airway 8.2 BP* disease 2444 malformation Contractures-developmental 6 Cases 436003 100 delay-Pierre Robin syndrome Congenital pulmonary 2414 Cases Contractures-ectodermal lymphangiectasia 2 Cases 1484 dysplasia-cleft lip/palate

Congenital pulmonary valve 39.3 BP* syndrome 3189 stenosis Contractures-webbed neck- 2 Cases 350 314002 micrognathia-hypoplastic nipples

3269 Congenital radioulnar synostosis Cases syndrome

12 Cases 1487 Cooks syndrome Congenital respiratory-biliary 35 Cases 2040 fistula 2 Cases 1488 Cooper-Jabs syndrome Congenital reticular 40 Cases 281190 ichthyosiform erythroderma Corneal dystrophy-perceptive 24 Cases 1490 0.03 I* deafness syndrome 290 Congenital rubella syndrome Corneal intraepithelial 0.35 BP* dyskeratosis-palmoplantar 19 Cases 290 Congenital rubella syndrome 352662 hyperkeratosis-laryngeal Congenital short bowel 43 Cases dyskeratosis syndrome 2301 syndrome 1.9 P* 199 Cornelia de Lange syndrome Congenital sideroblastic anemia- B-cell immunodeficiency-periodic 16 Cases 1.3 BP* 369861 199 Cornelia de Lange syndrome fever-developmental delay syndrome Corneodermatoosseous 7 Cases 3194 15 Cases syndrome 103908 Congenital sodium diarrhea Corpus callosum agenesis- 2 Cases 6 52055 intellectual disability-coloboma- Congenital stromal corneal 101068 Families micrognathia syndrome dystrophy 459074 Corpus callosum agenesis- 4 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 27 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Cortical blindness-intellectual 3 Cases 1541 Craniosynostosis, Boston type Families 1389 disability-polydactyly syndrome Cortical dysgenesis with Craniosynostosis, Herrmann- 2 Cases 12 Cases 2145 300570 pontocerebellar hypoplasia due Opitz type

to TUBB3 mutation Craniosynostosis, Philadelphia 1 Family 1527 Corticosteroid-sensitive aseptic 49 Cases type 54251 abscess syndrome Craniosynostosis-Dandy-Walker 4 Cases 300 1538 malformation-hydrocephalus

3071 Costello syndrome Cases syndrome

Craniosynostosis-anal anomalies- 9 Cases 85199 0.5 P* porokeratosis syndrome 201 Cowden syndrome Craniosynostosis-fibular aplasia 2 Cases 1533 4 Cases syndrome 1508 Coxoauricular syndrome Craniosynostosis-hydrocephalus- 2 Cases 47 Cases 171839 Arnold-Chiari malformation type 1509 Coxopodopatellar syndrome I-radioulnar synostosis syndrome 9 Cases Craniosynostosis-intracranial 3 Cases 1512 Crane-Heise syndrome 52054 calcifications syndrome 30 Cases Craniosynostosis- 1525 Cranio-osteoarthropathy 3 Cases 565858 microretrognathia-severe

20 Cases intellectual disability syndrome 1513 Craniodiaphyseal dysplasia 4 Cases 1528 Craniotelencephalic dysplasia Craniodigital-intellectual 5 Cases 1514 disability syndrome 0.1 BP* 205 Crigler-Najjar syndrome 60 Cases 1515 Cranioectodermal dysplasia 1.0 P* 205 Crigler-Najjar syndrome 1 Family 85168 Craniofacial conodysplasia 30 Cases 1545 Crisponi syndrome Craniofacial dysplasia-osteopenia 5 Cases 314555 syndrome 0.8 BP* 1461 Criss-cross heart Craniofacial dysplasia-short 8 Cases 459061 stature-ectodermal anomalies- 500

intellectual disability syndrome 2930 Cronkhite-Canada syndrome Cases

14 Cases 1516 Craniofacial dyssynostosis 12 Cases 2935 Crossed polysyndactyly Craniofacial-deafness-hand 3 Cases 1529 syndrome 0.9 BP* 207 Crouzon disease Craniofaciofrontodigital 4 Cases 363705 syndrome Crouzon syndrome-acanthosis 0.1 BP 93262 Craniofrontonasal dysplasia- 2 Cases nigricans syndrome 1521 Poland anomaly syndrome 11.0 I* 1546 Cryptococcosis 28 Cases 50814 Craniolenticulosutural dysplasia Cryptogenic multifocal ulcerous 60 Cases 468635 Craniometadiaphyseal dysplasia, 4 Cases stenosing enteritis 85184 wormian bone type Cryptomicrotia-brachydactyly- 2 Cases 1547 160 excess fingertip arch syndrome

1522 Craniometaphyseal dysplasia Cases Cryptorchidism-arachnodactyly- 3 Cases 1548 intellectual disability syndrome 1.0 I 1.96 I* 54595 Craniopharyngioma 1549 Cryptosporidiosis

2.0 P* Curly hair-acral keratoderma- 14 Cases 54595 Craniopharyngioma 307766 caries syndrome 4 Cases 1.0 P* 157832 Craniorhiny 1552 Currarino syndrome

1531 Craniosynostosis 24.3 BP* 1553 Curry-Jones syndrome 9 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 28 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

4.0 P* 0.5 BP* 96253 Cushing disease 213 Cystinosis

0.2 I* 14.0 P 96253 Cushing disease 214 Cystinuria

6.5 P* 5.0 P* 553 Cushing syndrome 214 Cystinuria

5.9 P 97 Cases 553 Cushing syndrome 75381 Cystoid macular dystrophy

0.15 I* Cytomegalovirus disease in 553 Cushing syndrome patients with impaired cell 25.5 P* 137698 Cushing syndrome due to mediated immunity deemed at 0.08 P* 189427 macronodular adrenal risk

hyperplasia 100 Cytophagic histiocytic Cutaneous collagenous 20 Cases 94087 Cases 280779 panniculitis vasculopathy Cytosolic phospholipase-A2 Cutaneous neuroendocrine 0.27 I 2 Cases 79140 477787 alpha deficiency associated carcinoma Cutaneous neuroendocrine 0.13 I* bleeding disorder 79140 3 Cases carcinoma 2437 Czeizel-Losonci syndrome Cutaneous neuroendocrine 4.0 P* 79140 13 Cases carcinoma 356978 D,L-2-hydroxyglutaric aciduria Cutaneous neuroendocrine 0.86 79140 80 Cases carcinoma 79315 D-2-hydroxyglutaric aciduria Cutaneous photosensitivity- 3 Cases 2881 1 Case lethal colitis syndrome 300536 DDOST-CDG 60 Cases 451607 Cutaneous pseudolymphoma DDX41-related hematologic 3

Cutis gyrata-acanthosis nigricans- 12 Cases 488647 malignancy predisposition Families 1555 craniosynostosis syndrome syndrome 0.1 BP* 40 Cases 209 Cutis laxa 79134 DEND syndrome

Cutis laxa with severe DIAPH1-related sensorineural 21 Cases 8 Cases 221145 pulmonary, gastrointestinal and 494444 hearing loss-thrombocytopenia

urinary anomalies syndrome 18 Cases 70 Cases 171719 Cutis laxa-Marfanoid syndrome 404546 DITRA

300 17 Cases Cutis marmorata telangiectatica 91131 DK1-CDG 1556 Cases congenita DNA2-related mitochondrial DNA 4 Cases 352470 0.1 P* deletion syndrome 2686 Cyclic neutropenia DNAJB2-related Charcot-Marie- 2 Cases 443950 Cyprus facial- 1 Family Tooth disease type 2 2674 6 neuromusculoskeletal syndrome DNAJB6-related limb-girdle 1.0 I* 34516 Families 400 Cystic echinococcosis muscular dystrophy D1

DNM1L-related encephalopathy 7.4 P* 11 Cases 586 Cystic fibrosis 330050 due to mitochondrial and

Cystic fibrosis-gastritis- 2 Cases peroxisomal fission defect 2575 5 Cases megaloblastic anemia syndrome 447737 DOCK2 deficiency Cystic hamartoma of lung and 3 Cases 2111 DONSON-related microcephaly- kidney 30 Cases Cystic leukoencephalopathy 50 Cases 572761 short stature-limb abnormalities 85136 without megalencephaly spectrum 0.75 BP 50 Cases 213 Cystinosis 79500 DOORS syndrome

18 Cases 213 Cystinosis 1.5 P* 86309 DPAGT1-CDG

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 29 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 9 Cases syndrome 79322 DPM1-CDG 0.27 I* 99970 Dedifferentiated liposarcoma 1 Case 263494 DPM3-CDG Deficiency in anterior pituitary 7 Cases DYNC1H1-related autosomal 293978 function-variable 37 Cases 209341 dominant childhood-onset immunodeficiency syndrome

proximal spinal muscular atrophy 20 Dehydrated hereditary DYRK1A-related intellectual 54 Cases 3202 Families 464306 stomatocytosis disability syndrome DYRK1A-related intellectual 2 19 Cases Delayed membranous cranial 268261 disability syndrome due to 3034 Families ossification 21q22.13q22.2 microdeletion Dacryocystitis-osteopoikilosis 5 Cases Delayed speech-facial 1562 6 Cases syndrome 3038 asymmetry-strabismus-ear lobe

Dahlberg-Borer-Newcomer 2 Cases creases syndrome 1563 syndrome 10 Cases 1627 Deletion 5q35 Dandy-Walker malformation- 5 Cases 1566 postaxial polydactyly syndrome Delta-sarcoglycan-related limb- 0.3 P* 219 3.4 P* girdle muscular dystrophy R6 218 Darier disease 714.0 I 99828 Dengue fever 40 Cases 2962 De Barsy syndrome 0.5 I* 99828 Dengue fever Deaf blind hypopigmentation 2 Cases 3214 syndrome, Yemenite type 0.25 P 93571 Dense deposit disease Deafness with labyrinthine 56 Cases 90024 aplasia, microtia, and 250

microdontia 1652 Dent disease Families

2 Cases 3241 Deafness-craniofacial syndrome 1.0 P* 99789 Dentin dysplasia type I Deafness-ear malformation- 4 Cases 3232 facial palsy syndrome 19

15 99791 Dentin dysplasia type II Families Deafness-enamel hypoplasia-nail 3220 Families defects syndrome Dentin dysplasia-sclerotic bones 1 Family 99792 Deafness-encephaloneuropathy- 2 Cases syndrome 254898 obesity-valvulopathy syndrome 14.5 P* 49042 Dentinogenesis imperfecta Deafness-epiphyseal dysplasia- 2 Cases 3218 short stature syndrome Dentinogenesis imperfecta type 14.6 P* 166260 Deafness-genital anomalies- 2 2 Cases 3224 metacarpal and metatarsal Dentinogenesis imperfecta-short 2 Cases synostosis syndrome 71267 stature-hearing loss-intellectual

Deafness-hypogonadism 5 Cases disability syndrome 90646 syndrome 300

3 220 Denys-Drash syndrome Cases

94064 Deafness-infertility syndrome Families

27.0 P* 1656 Dermatitis herpetiformis Deafness-intellectual disability 3 Cases 85321 syndrome, Martin-Probst type Dermatofibrosarcoma 10.0 P* 31112 Deafness-lymphedema-leukemia 20 Cases protuberans 3226 syndrome 2 Cases 1659 Dermatoleukodystrophy 5 Cases 3230 Deafness-oligodontia syndrome 0.55 I* 221 Dermatomyositis Deafness-onychodystrophy 50 Cases 3231 syndrome 6.0 P* 221 Dermatomyositis Deafness-small bowel 5 Cases 3217 diverticulosis-neuropathy Dermatoosteolysis, Kirghizian 5 Cases 1657 syndrome type 3239 Deafness-vitiligo-achalasia 2 Cases 86920 Dermatopathia pigmentosa 20 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 30 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families reticularis Dermatosparaxis Ehlers-Danlos 15 Cases 2.79 I* 1901 544 Diffuse large B-cell lymphoma syndrome 15 Cases Diffuse neonatal 70 Cases 79149 Dermochondrocorneal dystrophy 2123 hemangiomatosis 11 Cases Diffuse palmoplantar 1660 Dermoodontodysplasia 10 Cases 86918 keratoderma-acrocyanosis

50 Cases syndrome 1425 Desbuquois syndrome Digital extensor muscle aplasia- 3 Cases 2926 Desmin-related myopathy with 5 Cases polyneuropathy 84132 Mallory body-like inclusions 150 Dihydropteridine reductase 0.3 I* 226 Cases 873 Desmoid tumor deficiency

300 Dilated cardiomyopathy- 20 Desmoplastic small round cell 83469 Cases 2229 hypergonadotropic Families tumor hypogonadism syndrome Desmoplastic/nodular 0.01 I* Dimethylglycine dehydrogenase 1 Case 251863 243343 medulloblastoma deficiency 10 Cases 0.02 BP 35107 Desmosterolosis 227 Diphallia

Developmental and speech delay 14 Cases 33 Cases 313892 1681 Diprosopus due to SOX5 deficiency Developmental delay with Dislocation of the hip- 4 Cases 22 Cases 2412 329195 autism spectrum disorder and dysmorphism syndrome

gait instability 0.6 P* 79168 Disorder of bile acid synthesis Developmental delay-facial 26 Cases 369891 dysmorphism syndrome due to Disorder of sex development- 3 Cases 2983 MED13L deficiency intellectual disability syndrome Developmental malformations- 2 Cases 150 79107 Disseminated peritoneal deafness-dystonia syndrome 71274 Cases leiomyomatosis Dianzani autoimmune 30 Cases 275523 lymphoproliferative disease Distal 17p13.1 microdeletion 16 Cases 319171 18 Cases syndrome 66637 Diaphanospondylodysostosis Distal 17p13.3 microdeletion 16 Cases 261257 Diaphragmatic defect-limb 7 Cases syndrome 2141 deficiency-skull defect syndrome Distal 7q11.23 microdeletion 41 Cases 254351 Diaphragmatic hernia-short 2 Cases syndrome 527468 bowel-asplenia syndrome Distal 7q11.23 microduplication 5 Cases 261102 1.2 P* syndrome 628 Diastrophic dwarfism Distal Xq28 microduplication 9 Cases 293939 0.3 BP* syndrome 628 Diastrophic dwarfism 24 Cases 399096 Distal anoctaminopathy 18 Cases 370046 Didymosis aplasticosebacea 10.0 P 1146 Distal arthrogryposis type 1 5.25 I 146 Differentiated thyroid carcinoma 53 Cases 251515 Distal arthrogryposis type 10 2.0 I* 146 Differentiated thyroid carcinoma 33 Cases 329457 Distal arthrogryposis type 5D 1.0 P* 90060 Diffuse alveolar hemorrhage 4 Distal hereditary motor 139525 Families Diffuse cerebral and cerebellar neuropathy type 2 atrophy-intractable seizures- 4 Cases 404437 progressive microcephaly Distal hereditary motor 30 Cases 139552 syndrome neuropathy, Jerash type 30 Cases Distal limb deficiencies- 6 Cases 79456 Diffuse cutaneous mastocytosis 1307 micrognathia syndrome 544 Diffuse large B-cell lymphoma 43.0 P* 96148 Distal monosomy 10q 40 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 31 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

8 Cases 97.7 BP* 280325 Distal monosomy 12p 870 Down syndrome

150 2.5 BP 33069 Dravet syndrome 1590 Distal monosomy 13q Cases

Duane anomaly-myopathy- 2 Cases 50817 30 Cases scoliosis syndrome 1596 Distal monosomy 15q 10.0 P* 233 Duane retraction syndrome 34 Cases 1620 Distal monosomy 3p Duane retraction syndrome with 4 Cases 529574 35 Cases congenital deafness 96125 Distal monosomy 6p 0.2 BP* 235 Dubowitz syndrome 89 Cases 1642 Distal monosomy 9p 5.0 P* 98896 Duchenne muscular dystrophy Distal myopathy with anterior 4 Cases 178400 tibial onset 4.78 P 98896 Duchenne muscular dystrophy Distal myopathy with posterior 16 Cases 63273 leg and anterior hand 9.0 BP* 1203 Duodenal atresia involvement 7 Cases 9.0 P* 488650 Distal myopathy, Tateyama type 1203 Duodenal atresia

13 Cases 38 Cases 399103 Distal nebulin myopathy 314621 Duplication of the pituitary gland

Distal spinal muscular atrophy 28 Cases 300 139547 type 3 237 Duplication of urethra Cases

3248 Distal symphalangism Families 100

239 Dyggve-Melchior-Clausen disease Cases

23 Cases 314588 Distal tetrasomy 15q 7.8 P* 412 Dysbetalipoproteinemia 40 Cases 96102 Distal trisomy 10q 10.0 P 412 Dysbetalipoproteinemia 40 Cases 1745 Distal trisomy 6p Dyschondrosteosis-nephritis 1 Family 1765 2 Cases syndrome 3262 Dobrow syndrome 300 Dyschromatosis symmetrica 10 41 Cases Dominant dystrophic hereditaria 158676 Families epidermolysis bullosa, nails only 51 Cases 1766 Dysequilibrium syndrome Dominant hypophosphatemia 12 Cases 244305 with nephrolithiasis or 0.1 P* 1775 Dyskeratosis congenita osteoporosis 50 Cases Dysmorphism-pectus carinatum- 2 Cases 2143 Donnai-Barrow syndrome 2104 joint laxity syndrome 0.3 P* Dysmorphism-short stature- 255 Dopa-responsive dystonia 2 Cases 2282 deafness-disorder of sex

0.5 P development syndrome 255 Dopa-responsive dystonia Dysplasia epiphysealis 0.1 I 1822 Dopa-responsive dystonia due to 43 Cases hemimelica 70594 sepiapterin reductase deficiency 2 Cases 2204 Dysplastic cortical hyperostosis Dopamine beta-hydroxylase 21 Cases 230 deficiency Dysraphism-cleft lip/palate-limb 3 Cases 2476 0.5 BP reduction defects syndrome 3427 Double outlet left ventricle 16 Cases 85198 Dysspondyloenchondromatosis Double uterus-hemivagina-renal 60 Cases 3411 agenesis syndrome 12 Cases 210571 Dystonia 16 870 Down syndrome 95.0 BP

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 32 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 32 Cases brain atrophy-microcephaly- 412217 Dystonia-aphonia syndrome muscle weakness-optic atrophy Dystonia-parkinsonism- 11 Cases syndrome 521406 hypermanganesemia syndrome Early-onset progressive 3 Cases 0.7 P 1943 encephalopathy with migrant 303 Dystrophic epidermolysis bullosa continuous myoclonus 1.1 P* Early-onset progressive 303 Dystrophic epidermolysis bullosa encephalopathy-hearing loss- 3 Cases 500144 100 pons hypoplasia-brain atrophy Dystrophic epidermolysis bullosa 89843 Families syndrome pruriginosa Early-onset progressive 26 Cases encephalopathy-spastic ataxia- 6 Cases 199343 EAST syndrome 496756 distal spinal muscular atrophy 4 syndrome Early-onset progressive 293936 EDICT syndrome Families 6 Cases 352654 neurodegeneration-blindness-

1.11 BP* ataxia-spasticity syndrome 1896 EEC syndrome Early-onset seizures-distal limb 7 anomalies-facial dysmorphism- 12 Cases 505237 1897 EEM syndrome Families global developmental delay

syndrome Early-onset spastic ataxia- EMILIN-1-related connective 3 Cases 2 Cases 485418 313772 myoclonic epilepsy-neuropathy tissue disease syndrome 2 EPHB4-related lymphatic-related 568065 Families 19 Cases hydrops fetalis 391320 East Texas bleeding disorder

28220 3 Cases 496751 EVEN-plus syndrome 319218 Ebola hemorrhagic fever Cases

Ear-patella-short stature 67 Cases 2554 1.25 P* syndrome 1880 Ebstein malformation

80 Cases 1935 Early myoclonic encephalopathy 3.5 BP* 1880 Ebstein malformation

3 Cases 324290 Early-onset Lafora body disease Ectodermal dysplasia with natal 1 Family 69083 teeth, Turnpenny type 4 Early-onset X-linked optic 98890 Families Ectodermal dysplasia, 7 Cases atrophy 1818 trichoodontoonychial type Early-onset calcifying Ectodermal dysplasia-blindness 2 Cases 13 Cases 1806 556985 leukoencephalopathy-skeletal syndrome Ectodermal dysplasia-cutaneous 4 Cases dysplasia 247827 Early-onset epilepsy-intellectual syndactyly syndrome 5 Cases Ectodermal dysplasia- 488635 disability-brain anomalies 2 Cases 1883 sensorineural deafness syndrome Early-onset epileptic syndrome encephalopathy-cortical 3 Cases Ectodermal dysplasia-syndactyly 22 Cases 411986 247820 blindness-intellectual disability- syndrome 0.67 BP facial dysmorphism syndrome 448270 Ectopia cordis Early-onset familial noncirrhotic 3 Cases 494348 Ectopia lentis-chorioretinal 8 Cases portal hypertension 1884 Early-onset generalized limb- 0.4 P* dystrophy-myopia syndrome 256 Ectrodactyly-polydactyly 1 Family onset dystonia 1892 Early-onset myopathy-areflexia- syndrome 13 Cases 2 439212 respiratory distress-dysphagia Edinburgh malformation 1895 Families syndrome syndrome 2 Early-onset parkinsonism- 2379 Families 0.9 BP* intellectual disability syndrome 98249 Ehlers-Danlos syndrome

496641 Early-onset progressive diffuse 22 Cases 1902 Ehrlichiosis 50 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 33 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Cases 6 Cases 79106 Eiken syndrome 29.0 P* 73247 Eosinophilic esophagitis 5 Cases 228240 Elastoderma 34.4 P 73247 Eosinophilic esophagitis 0.4 BP* 289 Ellis Van Creveld syndrome 280

1.1 BP 2070 Eosinophilic gastroenteritis Cases 289 Ellis Van Creveld syndrome

350 Eosinophilic granulomatosis with 1.56 P* 183 96170 Emanuel syndrome Cases polyangiitis

Eosinophilic granulomatosis with 1.5 P 183 0.01 I* polyangiitis 180226 Embryonal carcinoma Eosinophilic granulomatosis with 0.18 I* 183 Embryonal tumor of 0.22 I* polyangiitis 251852 neuroepithelial tissue 0.2 I* 301 Ependymal tumor Emery-Dreifuss muscular 0.3 P* 261 dystrophy 3.85 301 Ependymal tumor 2 Cases 1927 Emery-Nelson syndrome 0.16 I* 251636 Ependymoma 11 Cases 1031 Enamel-renal syndrome Epibulbar lipodermoid- 1 Family Encephalocraniocutaneous 77 Cases 231742 preauricular appendage- 2396 lipomatosis polythelia syndrome Encephalopathy due to 400 15 Cases 527276 mitochondrial and peroxisomal 35125 Epidermal nevus syndrome Cases

fission defect 200 Encephalopathy due to 10 Cases 139406 302 Epidermodysplasia verruciformis Cases prosaposin deficiency 100 Encephalopathy due to sulfite 833 Cases 0.03 I* oxidase deficiency 46487 Epidermolysis bullosa acquisita

Encephalopathy-hypertrophic 1.8 P 1 Case 304 Epidermolysis bullosa simplex 319678 cardiomyopathy-renal tubular

disease syndrome 2.2 BP* 304 Epidermolysis bullosa simplex Endocrine-cerebro- 7 Cases 199332 osteodysplasia syndrome Epidermolysis bullosa simplex 2 Cases 412181 0.81 I* due to BP230 deficiency 454723 Endometrioid carcinoma of ovary Epidermolysis bullosa simplex 3 Cases 412189 6 due to exophilin 5 deficiency Endosteal hyperostosis, Worth 2790 Families Epidermolysis bullosa simplex 40 Cases type 257 with muscular dystrophy Endosteal sclerosis-cerebellar 4 Cases 6 85186 Epidermolysis bullosa simplex, hypoplasia syndrome 79401 Families Ogna type 2 Cases 1937 Eng-Strom syndrome Epidermolysis bullosa simplex, 19 Cases 89838 4.3 P* autosomal recessive K14 60015 Enlarged parietal foramina 1.68 BP 141077 Epignathus 3.7 P 60015 Enlarged parietal foramina Epilepsy-microcephaly-skeletal 2 Cases 1948 7 Cases dysplasia syndrome 83620 Enteric anendocrinosis 6 Cases 1951 Epilepsy-telangiectasia syndrome Enthesitis-related juvenile 5.7 P* 85438 idiopathic arthritis Epiphyseal dysplasia-hearing 2 Cases 1825 52 Cases loss-dysmorphism syndrome 449566 Eosinophilic angiocentric fibrosis 1 Family 79135 Episodic ataxia type 3 402035 Eosinophilic colitis 196

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 34 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 2 FASTKD2-related infantile 3 Cases 79136 Episodic ataxia type 4 Families 166105 mitochondrial

encephalomyopathy 7 Cases 22 Cases 211067 Episodic ataxia type 5 2492 FATCO syndrome

4 Cases FBLN1-related developmental 209967 Episodic ataxia type 6 3 Cases 404451 delay-central nervous system

7 Cases anomaly-syndactyly syndrome 209970 Episodic ataxia type 7 FGFR2-related bent bone 11 Cases 313855 Episodic ataxia with slurred 13 Cases dysplasia 401953 speech FKRP-related limb-girdle 1.0 P* 34515 186 muscular dystrophy R9 Epithelial recurrent erosion 293381 Cases 6 dystrophy 2045 FLOTCH syndrome Families

Epstein-Barr virus-associated 1.2 I 313920 gastric carcinoma 4 Cases 247790 FTH1-related iron overload 500

35687 Erdheim-Chester disease Cases 0.22 BP* 324 Fabry disease

6 Cases Facial dysmorphism-anorexia- 999 Ermine phenotype 3 Cases 1969 cachexia-eye and skin anomalies

200 syndrome

317 Erythrokeratodermia variabilis Cases Facial dysmorphism-

developmental delay-behavioral 19 Cases 284169 Erythrokeratodermia- 3 Cases abnormalities syndrome due to 476096 cardiomyopathy syndrome 10p11.21p12.31 microdeletion 24.3 BP* Facial dysmorphism- 1199 Esophageal atresia developmental delay-behavioral 10 Cases 466950 0.48 I* abnormalities syndrome due to 3318 Essential thrombocythemia WAC point mutation Facial dysmorphism- 0.02 I* 11 Cases 1957 Esthesioneuroblastoma 352712 immunodeficiency-livedo-short

2 Cases stature syndrome 785 Estrogen resistance syndrome Facial dysmorphism-lens 4 dislocation-anterior segment 80 Cases 412022 Families 51188 Ethylmalonic encephalopathy abnormalities-spontaneous

filtering blebs syndrome 0.1 P* 1959 Evans syndrome Facial dysmorphism- 3 Cases 1970 macrocephaly-myopia-Dandy- Exostoses-anetodermia- 1 Family 1962 Walker malformation syndrome brachydactyly type E syndrome Facial dysmorphism-shawl 2 Cases Extensor tendons of finger 2 Cases 1778 3294 scrotum-joint laxity syndrome anomalies Facial onset sensory and motor 47 Cases External auditory canal atresia- 85162 10 Cases neuronopathy 3023 vertical talus-hypertelorism 4 Cases syndrome 1973 Faciocardiorenal syndrome

0.13 I* 363579 Extragonadal germ cell tumor 4.5 P* 269 Facioscapulohumeral dystrophy

Extraskeletal myxoid 0.2 P* 209916 Fallot complex-intellectual chondrosarcoma 5 Cases 3304 disability-growth delay Extrasystoles-short stature- 2 Cases syndrome 1964 hyperpigmentation-microcephaly Familial Alzheimer-like prion 2 Cases syndrome 280397 disease Eye defects-arachnodactyly- 6 Cases 2725 10 cardiopathy syndrome 481662 Familial Chilblain lupus Families Eyebrow duplication-syndactyly 3 Cases 3172 syndrome 10 4 Cases 535458 Familial GPIHBP1 deficiency 306550 FADD-related immunodeficiency Families

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 35 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 6 Familial developmental 70 Cases 1799 Families 79293 Familial LCAT deficiency dysphasia

14 Familial dyskinesia and facial 18 Cases Familial acute necrotizing 324588 88619 Families myokymia encephalopathy 6 Familial encephalopathy with 6.0 P* 85110 Families 733 Familial adenomatous polyposis neuroserpin inclusion bodies

Familial adrenal hypoplasia with Familial episodic pain syndrome 3 Cases 28 Cases 95700 absent pituitary luteinizing 391392 with predominantly lower limb

hormone involvement 12 Familial episodic pain syndrome 21 Cases 228277 Familial anetoderma Families 391389 with predominantly upper body

involvement 3 Familial gastric type 1 5 Cases Familial apolipoprotein A5 464756 530849 Families neuroendocrine tumor deficiency 7 Familial hyperaldosteronism type 10 251274 Families Familial apolipoprotein C-II III 309020 Families deficiency 23 Cases 238475 Familial hypercholanemia 17

615 Familial atrial myxoma Families 28 Familial hyperthyroidism due to 424 Families mutations in TSH receptor Familial atrial tachyarrhythmia- 7 Cases 436242 infra-Hisian cardiac conduction Familial hypocalciuric 5.5 P 93372 disease hypercalcemia type 1 1 Family Familial infantile myoclonic 7 Cases 1551 Familial benign copper deficiency 352582 epilepsy 100 Familial isolated dilated 2.91 I* Familial calcium pyrophosphate 154 1416 Families cardiomyopathy deposition Familial isolated dilated 17.5 P* 154 4 Cases cardiomyopathy 1768 Familial caudal dysgenesis 100 Familial isolated Familial cavitary optic disc 17 Cases 99879 Families 464760 hyperparathyroidism anomaly Familial cerebral cavernous 15.0 P 10 221061 Familial isolated malformation 2238 Families hypoparathyroidism 5

1428 Familial chondromalacia patellae Families Familial isolated 2

2239 hypoparathyroidism due to Families

Familial chylomicronemia 0.97 P* agenesis of parathyroid gland 444490 syndrome 150 Familial isolated pituitary 4 314777 Cases Familial clubfoot due to adenoma 238578 Families 17q23.1q23.2 microduplication 2

Familial congenital mirror 75 Cases 411788 Familial isolated trichomegaly Families 238722 movements 2 Familial congenital nasolacrimal 4 Cases Familial lipase maturation factor 451612 535453 Families duct obstruction 1 deficiency Familial congenital palsy of 6 Cases 91498 40.0 BP* trochlear nerve 768 Familial long QT syndrome 11 Cases 319189 Familial cortical myoclonus Familial median cleft of the 8 Cases 401942 16 Cases upper and lower lips 53296 Familial cutaneous collagenoma 1.5 I* 618 Familial melanoma Familial cutaneous telangiectasia 24 Cases 313846 and oropharyngeal cancer Familial mesial temporal lobe 4 Cases 165805 predisposition syndrome epilepsy with febrile seizures

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 36 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

495930 Familial monosomy 7 syndrome Families Familial thoracic aortic aneurysm 22 Cases 91387 and aortic dissection Familial multiple discoid 44 Cases 22 Cases 538756 93953 Familial thyroglossal duct cyst fibromas 8 Cases Familial thyroid 2.67 I 922 Familial nasal acilia 95716 dyshormonogenesis Familial omphalocele syndrome 5 Cases Familial thyroid 4.0 P* 280403 95716 with facial dysmorphism dyshormonogenesis Familial or sporadic hemiplegic 10.0 P* 0.3 P* 569 84 Fanconi anemia migraine Familial osteodysplasia, 4 Cases 0.62 BP* 2769 84 Fanconi anemia Anderson type Familial papillary thyroid 2 Cases 0.3 P 97290 carcinoma with renal papillary 84 Fanconi anemia

neoplasia 200

Familial partial lipodystrophy, 20 Cases 2088 Fanconi-Bickel syndrome Cases 79084 Köbberling type Familial primary 200 96 Cases hypomagnesemia with 333 Farber disease 306516 Cases hypercalciuria and Fatal congenital hypertrophic 10 Cases nephrocalcinosis 439854 cardiomyopathy due to glycogen

Familial primary storage disease hypomagnesemia with 72 Cases 27 Cases 2196 hypercalciuria and 466 Fatal familial insomnia

nephrocalcinosis with severe Fatal infantile hypertonic 11 Cases 280553 ocular involvement myofibrillar myopathy Familial primary Fatal mitochondrial disease due hypomagnesemia with 110 7 Cases 168566 to combined oxidative 31043 hypercalciuria and Cases phosphorylation defect type 3 nephrocalcinosis without severe Fatal post-viral 2 Cases ocular involvement 391343 neurodegenerative disorder Familial primary 5 Fatty acyl-CoA reductase 1 3 Cases hypomagnesemia with 438178 34527 Families deficiency normocalciuria and Febrile infection-related epilepsy 1.0 P* normocalcemia 163703 syndrome Familial progressive cardiac 50 Cases 871 123 conduction defect 1305 Feingold syndrome Cases 3 Familial progressive hyper- and 280628 Families hypopigmentation 120

391641 Feingold syndrome type 1 Cases Familial progressive retinal 9 Cases 488197 dystrophy-iris coloboma- 7 Cases congenital cataract syndrome 391646 Feingold syndrome type 2

Familial reactive perforating 50 Cases 79147 Female infertility due to oocyte 16 Cases collagenosis 488191 meiotic arrest 5 Female infertility due to zona 4 Cases 231108 Familial rhabdoid tumor Families 404466 pellucida defect

5 Familial scaphocephaly 11 Cases Female restricted epilepsy with 168624 101039 Families syndrome, McGillivray type intellectual disability

80 62 Cases 51083 Familial short QT syndrome Families 1988 Femoral-facial syndrome

1.5 BP* 11 Cases 2019 Femur-fibula-ulna complex 166282 Familial sick sinus syndrome

Ferro-cerebro-cutaneous 3 Cases Familial steroid-resistant 13 Cases 397922 280406 syndrome nephrotic syndrome with

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 37 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Fetal akinesia deformation 0.6 BP* 300 994 sequence 2092 Focal dermal hypoplasia Cases

Fetal akinesia-cerebral and 3 Cases 363409 retinal hemorrhage syndrome Focal epilepsy-intellectual 7 Cases 1.6 BP* 352587 disability-cerebro-cerebellar 1915 Fetal alcohol syndrome malformation 147 40.0 P* 294 Fetal cytomegalovirus syndrome 398166 Focal facial dermal dysplasia Cases

2 Cases 465824 Fetal encasement syndrome Focal facial dermal dysplasia type 81 Cases 79133 800 I

1917 Fetal methylmercury syndrome Cases Focal facial dermal dysplasia type 22 Cases 398173 II Fetal valproate spectrum 1.02 BP* Focal facial dermal dysplasia type 20 Cases 1906 1807 disorder III Fever-associated acute infantile 11 Cases Focal facial dermal dysplasia type 21 Cases 464724 398189 liver failure syndrome IV 115 30 Cases 477650 Fibroblastic rheumatism 48918 Focal myositis Cases

20 Cases 2021 Fibrochondrogenesis Focal, segmental or multifocal 2.0 I* 1866 Fibrodysplasia ossificans 0.05 P dystonia 337 Focal, segmental or multifocal 11.7 P* progressiva 1866 Fibrodysplasia ossificans 0.078 P* dystonia 337 150 progressiva Fibrolamellar hepatocellular 0.025 I* 2048 Foix-Chavany-Marie syndrome Cases 401920 carcinoma 16 Follicular cholangitis and 5 Cases 300552 84090 Fibronectin glomerulopathy Families pancreatitis 37.0 P* 545 Follicular lymphoma 0.01 I* 2030 Fibrosarcoma 2.192 I* 545 Follicular lymphoma Fibular aplasia-ectrodactyly 50 Cases 1118 0.1 I* syndrome 228371 Foodborne botulism Fibular dimelia-diplopodia 11 Cases 1757 8 Cases syndrome 3219 Fountain syndrome 2.0 P* 93323 Fibular hemimelia Foveal hypoplasia-optic nerve 7

Fibulo-ulnar hypoplasia-renal 2 Cases 397618 decussation defect-anterior Families 2256 anomalies syndrome segment dysgenesis syndrome 29 Cases Foveal hypoplasia-presenile 11 Cases 3255 Filippi syndrome 2253 cataract syndrome Finger hyperphalangy-toe Fowler urethral sphincter 33 Cases 2 Cases 2795 369979 anomalies-severe pectus dysfunction syndrome 44 Cases excavatum syndrome 221126 Fowler vasculopaty 20 Cases 97232 Fingerprint body myopathy 32.5 P 908 Fragile X syndrome Finnish upper limb-onset distal 7 Cases 399086 2.4 BP* myopathy 908 Fragile X syndrome 30 Cases 79292 Fish-eye disease 20.0 P* 908 Fragile X syndrome Flat face-microstomia-ear 2 Cases 1968 30 Cases anomaly syndrome 137834 Frank-Ter Haar syndrome 30 Cases 98970 Fleck corneal dystrophy 0.2 BP* 2052 Fraser syndrome

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 38 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

10 Cases 309246 GM2 gangliosidosis, AB variant 130

834 Free sialic acid storage disease Cases GMPPB-related limb-girdle 2 Cases 363623 muscular dystrophy R19 100 1 Family 2053 Freeman-Sheldon syndrome Cases 2090 GMS syndrome

GNB5-related intellectual 22 Cases 1 Family 542306 disability-cardiac arrhythmia 85335 Fried syndrome syndrome 12 Cases 1.0 P 99672 Fried's tooth and nail syndrome 602 GNE myopathy

2.0 P* 16 Cases 95 Friedreich ataxia 2102 GTP cyclohydrolase I deficiency

14 Cases 10 Cases 1791 Frontofacionasal dysplasia 506358 Gabriele-de Vries syndrome

100 0.4 I 1826 Frontometaphyseal dysplasia Cases 570422 Galactose mutarotase deficiency

2.0 BP* 0.7 BP* 352 Galactosemia 250 Frontonasal dysplasia 2.1 I* Frontonasal dysplasia-alopecia- 5 Cases 352 Galactosemia 228390 genital anomalies syndrome 100

Frontonasal dysplasia-bifid nose- 11 Cases 351 Galactosialidosis Cases 521308 upper limb anomalies syndrome Frontonasal dysplasia-severe 3 Cases 97 Cases 306542 microphthalmia-severe facial 2065 Galloway-Mowat syndrome

clefting syndrome 3 Gamma-aminobutyric acid 3.0 P* 2066 Families 282 Frontotemporal dementia transaminase deficiency

7.0 BP* Gamma-glutamyl transpeptidase 7 Cases 2059 Fryns syndrome 33573 deficiency 2 Cases 120 2058 Fryns-Smeets-Thiry syndrome 100026 Gamma-heavy chain disease Cases

100

349 Fucosidosis Cases Gamma-sarcoglycan-related 0.2 P* 353 limb-girdle muscular dystrophy

11 Cases R5 2854 Fuhrmann syndrome 9.1 BP 79665 Gardner syndrome 5 Fukutin-related limb-girdle 206554 Families Gastric adenocarcinoma and muscular dystrophy R13 28 Cases 314022 proximal polyposis of the

40 Cases stomach 24 Fumaric aciduria 24 Cases 2069 Gastrocutaneous syndrome 38 Cases 2067 GAPO syndrome 13.0 P* 44890 Gastrointestinal stromal tumor GCGR-related 8 Cases 438274 hyperglucagonemia 1.0 I 44890 Gastrointestinal stromal tumor 0.75 BP* 354 GM1 gangliosidosis 1.0 I* 44890 Gastrointestinal stromal tumor 200

79255 GM1 gangliosidosis type 1 Cases 16.9 BP* 2368 Gastroschisis

50 Cases 1.7 I* 79256 GM1 gangliosidosis type 2 355 Gaucher disease

70 Cases 1.3 BP 79257 GM1 gangliosidosis type 3 355 Gaucher disease

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 39 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

1.0 P* 26.0 P* 77259 Gaucher disease type 1 182067 Glial tumor

0.01 P* 5.35 I* 77260 Gaucher disease type 2 182067 Glial tumor

0.05 P* 3.0 I 77261 Gaucher disease type 3 360 Glioblastoma

Gaucher disease- 2.52 I* 10 Cases 360 Glioblastoma 2072 ophthalmoplegia-cardiovascular

calcification syndrome 1.0 P 360 Glioblastoma 27 Cases 2623 Geleophysic dysplasia 0.01 I* 251582 Gliomatosis cerebri 2 Cases 2074 Gemignani syndrome 0.03 I* 251576 Gliosarcoma 300 Generalized arterial calcification 51608 Cases of infancy Global developmental delay- alopecia-macrocephaly-facial 5 Cases 544488 Generalized basal epidermolysis dysmorphism-structural brain 14 Cases 508529 bullosa simplex with skin anomalies syndrome

atrophy, scarring and hair loss Global developmental delay-lung 2 Cases Generalized eruptive 40 Cases 404476 cysts-overgrowth-Wilms tumor 411777 keratoacanthoma syndrome 40.0 P Global developmental delay- 98497 Genetic peripheral neuropathy neuro-ophthalmological 26 Cases 488613 500 abnormalities-seizures- Genetic primary 34526 Cases intellectual disability syndrome hypomagnesemia Global developmental delay- 3 Cases 15 Cases 73223 osteopenia-ectodermal defect 2075 Genitopalatocardiac syndrome syndrome 22 Cases Global developmental delay- 85201 Genitopatellar syndrome visual anomalies-progressive 6 Cases 480898 10 Cases cerebellar atrophy-truncal 93398 Genochondromatosis type 2 hypotonia syndrome 5 Cases 30 Cases 2077 German syndrome 141163 Glossopalatine ankylosis

50 Cases 0.005 I* 2078 Geroderma osteodysplastica 97280 Glucagonoma

Gerstmann-Straussler-Scheinker 0.0055 I Glutamate-cysteine ligase 10 Cases 356 33574 syndrome deficiency 50 Glutaryl-CoA dehydrogenase 1.0 BP 25 643 Giant axonal neuropathy Families deficiency Glutathione synthetase 70 Cases 32 0.02 I* deficiency 251579 Giant cell glioblastoma 0.17 P* 407 Glycine encephalopathy Gingival fibromatosis-facial 2 Cases 2025 Glycogen storage disease due to 84 Cases dysmorphism syndrome 34587 2 LAMP-2 deficiency Gingival fibromatosis-progressive 2027 Families Glycogen storage disease due to 0.8 BP* deafness syndrome 365 acid maltase deficiency 2.5 P* Glycogen storage disease due to 3.0 P* 358 Gitelman syndrome 365 acid maltase deficiency Glaucoma secondary to Glycogen storage disease due to 12 Cases 1.75 BP 238763 spherophakia/ectopia lentis and 420429 acid maltase deficiency, late-

megalocornea onset Glaucoma-ectopia lentis- Glycogen storage disease due to 3 Cases 1.0 BP 2084 microspherophakia-stiff joints- 364 glucose-6-phosphatase

short stature syndrome deficiency

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 40 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Glycogen storage disease due to 7 Cases 1.0 BP* 2095 Gorlin-Chaudhry-Moss syndrome 79258 glucose-6-phosphatase

deficiency type Ia 5.0 P* 39812 Graft versus host disease Glycogen storage disease due to 150

79259 glucose-6-phosphatase Cases 7 Cases 79094 Grange syndrome deficiency type Ib Glycogen storage disease due to 0.1 BP 1 Family 367 glycogen branching enzyme 2097 Grant syndrome

deficiency 0.85 I* Glycogen storage disease due to 900 Granulomatosis with polyangiitis 16 Cases 2089 hepatic glycogen synthase 9.0 P* 900 Granulomatosis with polyangiitis deficiency Glycogen storage disease due to 1.0 BP* 50 Cases 264580 liver phosphorylase kinase 33111 Granulomatous slack skin

deficiency 60 Cases Glycogen storage disease due to 721 Gray platelet syndrome 4 Cases 137625 muscle and heart glycogen Grayson-Wilbrandt corneal 1 Family 293375 synthase deficiency dystrophy Glycogen storage disease due to 1 Case 10 Cases 99849 1426 Greenberg dysplasia muscle beta-enolase deficiency Glycogen storage disease due to 100 150

371 muscle phosphofructokinase Cases 381 Griscelli syndrome Cases

deficiency Glycogen storage disease due to 30 Cases 20 Cases 715 muscle phosphorylase kinase 79476 Griscelli syndrome type 1

deficiency 102 Glycogen storage disease due to 30 79477 Griscelli syndrome type 2 Cases 713 phosphoglycerate kinase 1 Families

deficiency 13 Cases Glycogen storage disease due to 79478 Griscelli syndrome type 3 50 Cases 97234 phosphoglycerate mutase Growth and developmental deficiency delay-hypotonia-vision 2 Cases Glycogen storage disease due to 1.0 BP* 391348 370 impairment-lactic acidosis phosphorylase kinase deficiency syndrome Glycogen storage disease with 1 Case Growth delay due to insulin-like 5 Cases 263297 severe cardiomyopathy due to 73272 growth factor type 1 deficiency glycogenin deficiency Growth delay-hydrocephaly-lung 4 Cases 0.025 I 3035 329984 Goblet cell carcinoma hypoplasia syndrome

Growth delay-intellectual 6 Cases Goldberg-Shprintzen megacolon 24 Cases 541423 66629 disability-hepatopathy syndrome syndrome Growth retardation-mild 2 Cases 50 Cases 391366 developmental delay-chronic 53540 Goldmann-Favre syndrome hepatitis syndrome 200 Grubben-de Cock-Borghgraef 3 Cases 1986 Gollop-Wolfgang complex Cases 2101 syndrome

Guanidinoacetate 80 Cases 241 382 methyltransferase deficiency 169105 Good syndrome Cases 1.45 I 2103 Guillain-Barré syndrome

3 Cases 65798 Goodman syndrome 1.4 I* 2103 Guillain-Barré syndrome

300 3.5 P* 73 Gorham-Stout disease Cases 2103 Guillain-Barré syndrome

3 Cases 2.0 P* 2957 Guttmacher syndrome 377 Gorlin syndrome

200 1.1 P Gyrate atrophy of choroid and 377 Gorlin syndrome 414 Cases retina

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 41 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Gómez-López-Hernández 36 Cases Heart defects-limb shortening 2 Cases 1532 1354 syndrome syndrome 100 2

168569 H syndrome Cases 1350 Heart-hand syndrome type 2 Families

6 3 Cases 1342 Heart-hand syndrome type 3 73229 HANAC syndrome Families

Heart-hand syndrome, Slovenian 14 Cases 168796 2 Cases type 2119 HEC syndrome 100 Helicoid peripapillary 2 86813 Cases HNRNPDL-related limb-girdle chorioretinal degeneration 55596 Families muscular dystrophy D3 3 Cases 562509 Heme oxygenase-1 deficiency 37 Cases 391417 HSD10 disease 100 Hemidystonia-hemiatrophy 5 Cases 306741 Cases 85295 HSD10 disease, atypical type syndrome

3 Cases 12 Cases 391457 HSD10 disease, neonatal type 141148 Hemifacial myohyperplasia

HTRA1-related autosomal Hemihyperplasia-multiple 10 Cases 21 Cases 276280 482077 dominant cerebral small vessel lipomatosis syndrome

disease 4.15 P* 2130 Hemimelia 60 Cases 99803 Haddad syndrome Hemiparkinsonism-hemiatrophy 68 Cases 306669 100 syndrome

2342 Haim-Munk syndrome Cases 74 Cases 79230 Hemochromatosis type 2

8 Cases 33 Cases 2107 Hall-Riggs syndrome 225123 Hemochromatosis type 3

150 200

2108 Hallermann-Streiff syndrome Cases 139491 Hemochromatosis type 4 Cases

2 Cases 10 Cases 2109 Hallermann-Streiff-like syndrome 280615 Hemoglobinopathy Toms River

Hallux varus-preaxial 2 Cases 7 2110 Hemolytic anemia due to polysyndactyly syndrome 86817 Families adenylate kinase deficiency Hamel cerebro-palato-cardiac 4 Cases 93946 syndrome Hemolytic anemia due to 50 Cases 200 712 glucophosphate isomerase

457 Harlequin ichthyosis Cases deficiency

Hemolytic anemia due to 3 Cases 90030 100 glutathione reductase deficiency

199282 Harlequin syndrome Cases Hemolytic anemia due to red cell 5.0 P* 766 pyruvate kinase deficiency 3 Cases Hemolytic uremic syndrome with 47 Cases 2115 Harrod syndrome 357008 DGKE deficiency 4.2 P 6.25 I* 2116 Hartnup disease 448 Hemophilia

17 Cases 7.7 P* 2117 Hartsfield syndrome 448 Hemophilia

5 4.85 P 2118 Hawkinsinuria Families 98878 Hemophilia A

8.0 P* Hearing loss-familial salivary 98878 Hemophilia A 2 Cases 3225 gland insensitivity to aldosterone 11.25 BP 98878 Hemophilia A syndrome Heart defect-tongue hamartoma- 4 Cases 3.0 P* 1338 98879 Hemophilia B polysyndactyly syndrome

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 42 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 1.665 BP of vitamin K-dependent clotting Families 98879 Hemophilia B factors Hemorrhagic disease due to Hereditary cryohydrocytosis with 53 Cases 4 Cases 398088 178396 alpha-1-antitrypsin Pittsburgh normal stomatin

mutation Hereditary cryohydrocytosis with 3 Cases 168577 Hemorrhagic fever-renal 0.74 I* reduced stomatin 340 syndrome 1.5 I* 26106 Hereditary diffuse gastric cancer Hemorrhagic fever-renal 37.0 P* 340 syndrome Hereditary diffuse 7 Cases leukoencephalopathy with 27 Cases 324632 Hendra virus infection 313808 axonal spheroids and pigmented 50 Cases glia 2136 Hennekam syndrome Hereditary fibrosing 3 Cases poikiloderma-tendon 15 Cases 2135 Hennekam-Beemer syndrome 221043 contractures-myopathy- Hepatic fibrosis-renal cysts- 4 Cases pulmonary fibrosis syndrome 2031 30 Cases intellectual disability syndrome 90045 Hereditary folate malabsorption 11.0 P* 890 Hepatic veno-occlusive disease 5.0 P* 469 Hereditary fructose intolerance Hepatic veno-occlusive disease- 28 Cases 79124 Hereditary hemorrhagic 16.0 P* immunodeficiency syndrome 774 Hepatitis B reinfection following 2.0 P* telangiectasia 90073 150 liver transplantation 40.0 P* 3197 Hereditary hyperekplexia Cases 402823 Hepatitis delta

0.02 I* Hereditary hyperferritinemia- 64 Cases 449 Hepatoblastoma 163 cataract syndrome 0.54 Hereditary hypotrichosis with 4 Cases 449 Hepatoblastoma 217407 recurrent skin vesicles 15.0 P* Hereditary inclusion body 17 Cases 88673 Hepatocellular carcinoma 324381 myopathy type 4 Hereditary inclusion body 3.221 I* 21 Cases 88673 Hepatocellular carcinoma 79091 myopathy-joint contractures-

Hepatoencephalopathy due to ophthalmoplegia syndrome 2 Cases 200 137681 combined oxidative Hereditary leiomyomatosis and 523 Cases phosphorylation defect type 1 renal cell cancer 40 Cases 95159 Hepatoerythropoietic porphyria 120 Hereditary motor and sensory Hereditary North American 36 Cases 90117 Cases 168583 neuropathy, Okinawa type Indian childhood cirrhosis 10 Hereditary acrokeratotic 41 Cases Hereditary myopathy with early 2907 178464 Families poikiloderma respiratory failure

5.0 P* 91378 Hereditary angioedema Hereditary myopathy with lactic 19 Cases 43115 acidosis due to ISCU deficiency Hereditary arterial and articular 16 Cases 289601 9 multiple calcification syndrome Hereditary neurocutaneous 1062 Families Hereditary breast and ovarian 25.0 P* malformation 145 cancer syndrome Hereditary neuropathy with 3.5 P* 2 640 Hereditary bullous dystrophy, liability to pressure palsies 1867 Families macular type 16 Cases 279943 Hereditary neutrophilia

350 Hereditary cerebral hemorrhage 85458 Cases 20 Cases with amyloidosis 30 Hereditary orotic aciduria

2 0.43 P* 676 Hereditary chronic pancreatitis 79141 Hereditary painful callosities Families

98434 Hereditary combined deficiency 30 476102 Hereditary pediatric Behçet-like 13 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 43 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families disease with neutropenia 19 0.3 I Hereditary persistence of alpha- 1930 Herpes simplex virus encephalitis 168615 Families fetoprotein Herpes simplex virus stromal 16.0 P* 137599 Hereditary pheochromocytoma- 0.3 I keratitis 29072 paraganglioma 1.0 P* 189 Hidrotic ectodermal dysplasia Hereditary progressive mucinous 18 Cases 158025 histiocytosis Hidrotic ectodermal dysplasia, 6 Cases 1808 Hereditary sclerosing 9 Cases Christianson-Fourie type 221039 poikiloderma, Weary type Hidrotic ectodermal dysplasia, 4 Cases 1809 Hereditary sensorimotor Halal type 4 Cases 280598 neuropathy with hyperelastic High bone mass osteogenesis 2 Cases 314029 skin imperfecta Hereditary sensory and 5 Cases High myopia-sensorineural 7 Cases 320385 autonomic neuropathy due to 363396 deafness syndrome TECPR2 mutation High-grade dysplasia in patients 36.0 P* 2 231080 Hereditary sensory and with Barrett esophagus 139564 Families 10.9 BP* autonomic neuropathy type 1B 388 Hirschsprung disease

Hereditary sensory and 35 Cases Hirschsprung disease-deafness- 2 Cases 970 2155 autonomic neuropathy type 2 polydactyly syndrome Hereditary sensory and 4 Cases Hirschsprung disease-nail 314381 3 Cases autonomic neuropathy type 6 2153 hypoplasia-dysmorphism Hereditary sensory and 3 Cases 391397 syndrome autonomic neuropathy type 7 Hirschsprung disease-type D 4 Cases 11 2150 Hereditary sensory and brachydactyly syndrome 478664 Families Histidinuria-renal tubular defect 5 Cases autonomic neuropathy type 8 2158 syndrome Hereditary sensory and 4 Cases Histiocytic and dendritic cell 0.05 I* 139573 autonomic neuropathy with 98287 tumor deafness and global delay 2.4 I* 6 98293 Hodgkin lymphoma Hereditary sensory neuropathy- 456318 Families 46.9 deafness-dementia syndrome 98293 Hodgkin lymphoma

4.8 P* 3 Cases 685 Hereditary spastic paraplegia 93970 Holmes-Gang syndrome

4.2 P Holocarboxylase synthetase 0.5 BP* 685 Hereditary spastic paraplegia 79242 deficiency Hereditary thermosensitive 1 Family 13.4 BP* 84093 2162 Holoprosencephaly neuropathy Hereditary thrombocytopenia 9 Cases Holoprosencephaly- 11 Cases 480851 2163 with early-onset myelofibrosis craniosynostosis syndrome 150 Holoprosencephaly-radial heart 4 Cases 3467 Hereditary xanthinuria Cases 3186 renal anomalies syndrome

0.7 BP* 9.05 I* 392 Holt-Oram syndrome 3467 Hereditary xanthinuria

3 Cases Heritable pulmonary arterial 0.08 P* 2167 Holzgreve syndrome 275777 hypertension Homocystinuria without 73 Cases 0.15 P 622 79430 Hermansky-Pudlak syndrome methylmalonic aciduria

Homozygous familial 0.1 P Hermansky-Pudlak syndrome 2 Cases 391665 231531 hypercholesterolemia type 7 33 Cases Hermansky-Pudlak syndrome 6 Cases 3322 Hoyeraal-Hreidarsson syndrome 231537 type 8 30 Cases Hermansky-Pudlak syndrome 2 Cases 228116 Hughes-Stovin syndrome 280663 type 9 56970 Human prion disease 0.15 I* 183678 Hermansky-Pudlak syndrome 40 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 44 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 30 Cases 79155 Hydroxykynureninuria 0.3 P* 56970 Human prion disease 2 Cases 309147 Hyper-beta-alaninemia 150

3265 Humero-radial synostosis Cases Hyperammonemic 4 Cases 401948 encephalopathy due to carbonic

30 Cases anhydrase VA deficiency 3266 Humero-radio-ulnar synostosis Hyperandrogenism due to 11 Cases 168588 5 Cases cortisone reductase deficiency 94056 Humero-ulnar synostosis 2 Cases 276405 Hyperbiliverdinemia 5 Cases 3383 Humerus trochlea aplasia Hypercholesterolemia due to 24 Cases Hunter-McAlpine 10 Cases 209902 cholesterol 7alpha-hydroxylase 97340 craniosynostosis deficiency Hypercoagulability syndrome 0.38 I 2 399 Huntington disease due to 83639 Families 12.0 P* glycosylphosphatidylinositol 399 Huntington disease deficiency 2.7 P Hyperekplexia-epilepsy 4 Cases 399 Huntington disease 163985 syndrome 50 1.5 P* 168956 Hypereosinophilic syndrome 98934 Huntington disease-like 2 Families Hypergonadotropic 3 Cases Huntington disease-like 2410 hypogonadism-cataract 10 Cases 401901 syndrome due to C9ORF72 syndrome 200 expansions Hyperimmunoglobulinemia D 0.5 P* 343 Cases 93473 Hurler syndrome with periodic fever

0.7 BP* Hyperinsulinism due to HNF1A 2 Cases 93473 Hurler syndrome 324575 deficiency Hutchinson-Gilford progeria 0.025 BP Hyperinsulinism due to INSR 10 Cases 740 263458 syndrome deficiency Hutchinson-Gilford progeria 0.005 P Hyperinsulinism due to UCP2 2 Cases 740 276556 syndrome deficiency 150 Hyperinsulinism due to short 10 Cases 498474 Hyaline fibromatosis syndrome Cases 71212 chain 3-hydroxylacyl-CoA

dehydrogenase deficiency Hydrocephalus with stenosis of 1.7 BP 0.5 P* 2182 682 Hyperkalemic periodic paralysis the aqueduct of Sylvius Hydrocephalus with stenosis of 1.7 P Hyperkeratosis- 10 Cases 2182 1336 the aqueduct of Sylvius hyperpigmentation syndrome Hydrocephalus-blue sclerae- 1 Family Hypermobile Ehlers-Danlos 12.5 P* 2186 285 nephropathy syndrome syndrome Hydrocephalus-costovertebral Hyperornithinemia- 111 8 Cases 2180 dysplasia-Sprengel anomaly 415 hyperammonemia- Cases

syndrome homocitrullinuria syndrome Hydrocephalus-obesity- 2 Cases Hyperostosis corticalis 35 Cases 2183 3416 hypogonadism syndrome generalisata Hydrocephaly-cerebellar 2 Cases 13 Cases 1397 443098 Hyperostosis cranialis interna agenesis syndrome 100 Hydrocephaly-low insertion 2 Cases Hyperparathyroidism-jaw tumor 2184 99880 Cases umbilicus syndrome syndrome Hydrocephaly-tall stature-joint 2 Cases 2181 Hyperphenylalaninemia due to 6 Cases laxity syndrome 508523 Hydrops-lactic acidosis- DNAJC12 deficiency 1 Case 528091 sideroblastic anemia- Hyperphenylalaninemia due to 0.2 P 238583 multisystemic failure syndrome tetrahydrobiopterin deficiency 247262 Hyperphosphatasia-intellectual 24 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 45 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families disability syndrome dysfunction-ichthyosis- 25 Cases xerostomia syndrome 1519 Hypertelorism, Teebi type Hypohidrosis-enamel hypoplasia- 12 Cases 3 363523 palmoplantar keratoderma- Hypertelorism-hypospadias- 2211 Families intellectual disability syndrome polysyndactyly syndrome Hypohidrotic ectodermal 6.7 P* 238468 Hypertelorism-microtia-facial 9 Cases dysplasia 2213 clefting syndrome Hypohidrotic ectodermal 0.2 BP* 98813 Hypertelorism-preauricular dysplasia with immunodeficiency 13 Cases 293958 sinus-punctual pits-deafness Hypohidrotic ectodermal 3 Cases syndrome 1882 dysplasia-hypothyroidism-ciliary

28 Cases dyskinesia syndrome 2220 Hypertrichosis cubiti Hypoinsulinemic hypoglycemia 5 Cases 293964 100 and body hemihypertrophy Hypertrichosis lanuginosa 2222 Cases 1.0 P* congenita 681 Hypokalemic periodic paralysis

Hypertrichosis-acromegaloid 27 Cases Hypomandibular faciocranial 3 Cases 966 1790 facial appearance syndrome dysostosis Hypertrichotic Hypomyelinating 50 Cases 1517 osteochondrodysplasia, Cantu leukodystrophy-ataxia- 8 Cases 137639 type hypodontia-hypomyelination Hypertrophic cardiomyopathy syndrome 3 Cases 324525 and renal tubular disease due to Hypomyelination neuropathy- 9 Cases 2680 mitochondrial DNA mutation arthrogryposis syndrome 12 Cases Hypomyelination with atrophy of 19 Cases 2224 Hypertryptophanemia 139441 basal ganglia and cerebellum Hyperuricemia-pulmonary 4 Hypomyelination with brain 13 Cases 363694 hypertension-renal failure- Families 363412 stem and spinal cord

alkalosis syndrome involvement and leg spasticity Hyperzincemia and 18 Cases Hypomyelination-cerebellar 251523 4 Cases hypercalprotectinemia 447893 atrophy-hypoplasia of the corpus

Hypo- and hypermelanotic callosum syndrome cutaneous macules-retarded 14 Cases Hypomyelination-congenital 10 Cases 2435 85163 growth-intellectual disability cataract syndrome syndrome Hypoparathyroidism- 180

3.3 P* 2237 sensorineural deafness-renal Cases 429 Hypochondroplasia disease syndrome 200 Hypopigmentation-punctate 6 Hypocomplementemic urticarial 36412 Cases 324561 palmoplantar keratoderma Families vasculitis syndrome Hypoglossia-hypodactyly 47 Cases 0.2 P* 989 722 Hypoplasminogenemia syndrome Hypogonadism-mitral valve 18.0 BP 2 Cases 2248 Hypoplastic left heart syndrome 2233 prolapse-intellectual disability

syndrome 15.1 BP* 2248 Hypoplastic left heart syndrome Hypogonadotropic 6 Cases 2230 hypogonadism-frontoparietal Hypoplastic pancreas-intestinal 16 Cases alopecia syndrome 293864 atresia-hypoplastic gallbladder

Hypogonadotropic syndrome 2 Cases 2235 hypogonadism-retinitis 3.3 BP* 98723 Hypoplastic right heart syndrome pigmentosa syndrome Hypogonadotropic Hyposmia-nasal and ocular hypogonadism-severe 2 Cases 4 Cases 2250 hypoplasia-hypogonadotropic 293967 microcephaly-sensorineural hypogonadism syndrome hearing loss-dysmorphism Hypospadias-intellectual 3 Cases syndrome 2261 disability, Goldblatt type Hypohidrosis-electrolyte 22 Cases 528105 syndrome imbalance-lacrimal gland 137908 Hypotonia with lactic acidemia 4 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 46 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families and hyperammonemia Ichthyosis-oral and digital 2 Cases 2272 22 Cases anomalies syndrome 163690 Hypotonia-cystinuria syndrome 16

Hypotonia-failure to thrive- 2 Cases 88621 Ichthyosis-prematurity syndrome Families 79507 microcephaly syndrome Ichthyosis-short stature- 38 Cases 7 Cases 55654 Hypotrichosis simplex 363992 brachydactyly-

Hypotrichosis with juvenile 50 Cases microspherophakia syndrome 1573 8.0 P macular degeneration 930 Idiopathic achalasia Hypotrichosis-deafness 1 Case 330029 0.77 I syndrome 930 Idiopathic achalasia Hypotrichosis-intellectual 2 Cases 2266 100 disability, Lopes type Idiopathic acute eosinophilic Hypotrichosis-lymphedema- 724 Cases 4 Cases pneumonia 69735 telangiectasia-renal defect Idiopathic acute transverse 0.25 I* syndrome 139423 Hypotrichosis-osteolysis- myelitis 2 Cases 307936 periodontitis-palmoplantar 0.4 P* 88 Idiopathic aplastic anemia keratoderma syndrome 66 Cases 30.0 P* 2268 ICF syndrome 33208 Idiopathic hypersomnia

IL21-related infantile 3 Cases Idiopathic intracranial 14.0 P* 477661 238624 inflammatory bowel disease hypertension 28 Cases 1.5 BP* 85173 IMAGe syndrome 45452 Idiopathic neonatal atrial flutter

75 Cases Idiopathic pleuroparenchymal 37 Cases 209981 IRIDA syndrome 494428 fibroelastosis 30 Cases Idiopathic pulmonary arterial 1.1 P* 209943 IRVAN syndrome 275766 hypertension ISPD-related limb-girdle 8 Cases 11.5 P* 352479 2032 Idiopathic pulmonary fibrosis muscular dystrophy R20 2 3.81 I* 2032 Idiopathic pulmonary fibrosis 439254 ITM2B amyloidosis Families

Idiopathic pulmonary 0.0425 I* 99931 ITPA-related lethal infantile hemosiderosis 7 Cases 457375 neurological disorder with Idiopathic/heritable pulmonary 1.0 P* 422 cataract and cardiac involvement arterial hypertension 4 IgG4-related retroperitoneal 0.35 I* 49041 2307 IVIC syndrome Families fibrosis

Ileal pouch anal anastomosis 3.0 P* 238621 180 related faecal incontinence

254509 Iatrogenic botulism Cases 6.67 BP* 42062 Iminoglycinuria

Ichthyosis follicularis-alopecia- 40 Cases 6.68 P* 2273 42062 Iminoglycinuria photophobia syndrome Ichthyosis hystrix of Curth- 10 Cases 79503 Immune dysregulation- Macklin inflammatory bowel disease- 80 Cases 238569 Ichthyosis-alopecia-eclabion- arthritis-recurrent infections 4 Cases 2269 ectropion-intellectual disability syndrome

syndrome Immune dysregulation- Ichthyosis-hepatosplenomegaly- inflammatory bowel disease- 7 Cases 2 Cases 529977 2274 cerebellar degeneration arthritis-recurrent infections-

syndrome lymphopenia syndrome Ichthyosis-hypotrichosis 11 Cases Immune dysregulation- 150 91132 syndrome 37042 polyendocrinopathy- Cases

Ichthyosis-intellectual disability- enteropathy-X-linked syndrome 4 Cases 2278 dwarfism-renal impairment 25.0 P* 3002 Immune thrombocytopenia syndrome

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 47 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 6.75 I* anomalies-hyperkinetic 3002 Immune thrombocytopenia movements-developmental 300 delay syndrome Immune-mediated necrotizing 206569 Cases Infantile inflammatory bowel myopathy 3 Cases 565788 disease with neurological

Immunodeficiency by defective 30 Cases involvement 34592 expression of MHC class I Infantile multisystem neurologic- 2 Cases 456312 179 endocrine-pancreatic disease Immunodeficiency by defective 572 Cases 0.67 BP* expression of MHC class II 2591 Infantile myofibromatosis

Immunodeficiency due to CD25 2 Cases 150 169100 deficiency 35069 Infantile neuroaxonal dystrophy Cases

Immunodeficiency due to MASP- 1 Case 331187 2 deficiency Infantile onset panniculitis with 4 Cases Immunodeficiency due to ficolin3 1 Case 251304 uveitis and systemic 331190 deficiency granulomatosis Immunodeficiency due to Infantile spasms-broad thumbs 2 Cases 49 Cases 3173 70592 interleukin-1 receptor-associated syndrome

kinase-4 deficiency Infantile spasms-psychomotor 35 retardation-progressive brain 4 Cases Immunodeficiency with factor I 263410 200418 Families atrophy-basal ganglia disease anomaly syndrome Imperforate oropharynx- 14 2 Cases Infantile-onset X-linked spinal 2759 costovertebral anomalies 1145 Families muscular atrophy syndrome 17 Incessant infant ventricular 1.5 BP* Infantile-onset ascending 45453 293168 Families tachycardia hereditary spastic paralysis Inclusion body myopathy with 26

52430 Paget disease of bone and Families Infantile-onset axonal motor and sensory neuropathy-optic 2 Cases frontotemporal dementia 457205 0.5 P* atrophy-neurodegenerative 611 Inclusion body myositis syndrome Infantile-onset generalized 1.2 BP* 8 Cases 464 Incontinentia pigmenti 494526 dyskinesia with orofacial

Infant acute respiratory distress 3.5 I* involvement 70587 Infantile-onset mesial temporal syndrome 3 Cases Infant acute respiratory distress 20.0 P* 391316 lobe epilepsy with severe 70587 syndrome cognitive regression Infantile-onset periodic fever- 0.2 BP* 5 Cases 178478 Infant botulism 500062 panniculitis-dermatosis

syndrome 0.3 I* 178478 Infant botulism Infantile-onset pulmonary 5 Cases 572428 alveolar proteinosis- Infantile cerebellar-retinal 11 Cases 313850 hypogammaglobulinemia degeneration Infantile-onset spinocerebellar 29 Cases Infantile cerebral and cerebellar 1186 5 Cases ataxia 402364 atrophy with postnatal Inflammatory bowel disease- progressive microcephaly 1 Case 529980 recurrent sinopulmonary Infantile choroidocerebral 10 Cases 1313 infections syndrome calcification syndrome 140 200 Inflammatory pseudotumor of 90003 Cases 199267 Infantile digital fibromatosis Cases the liver

10 Cases 16 Cases 254504 Inhalational botulism 238455 Infantile dystonia-parkinsonism

Inherited congenital spastic 17 Cases Infantile hypertrophic 210141 2 Cases tetraplegia 352563 cardiomyopathy due to MRPL44 1.9 BP* deficiency 79361 Inherited epidermolysis bullosa

522077 Infantile hypotonia-oculomotor 11 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 48 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 0.8 P* hyperkinetic movement-truncal 79361 Inherited epidermolysis bullosa ataxia syndrome 50.0 BP* Intellectual disability-hypoplastic 63259 Iniencephaly 3 Cases 1495 corpus callosum-preauricular tag

404 syndrome

411593 Insulin autoimmune syndrome Cases Intellectual disability-hypotonia- 2 Cases 314575 brachycephaly-pyloric stenosis-

0.25 I cryptorchidism syndrome 97279 Insulinoma Intellectual disability- Intellectual disability syndrome 35 Cases macrocephaly-hypotonia- 16 Cases 464311 457279 due to a DYRK1A point mutation behavioral abnormalities Intellectual disability, Birk-Barel 1 Family syndrome 166108 Intellectual disability-muscle type 3 Cases Intellectual disability, Buenos- 5 Cases 457365 weakness-short stature-facial 3079 Aires type dysmorphism syndrome Intellectual disability-myopathy- 2 Cases 2 Cases 3080 Intellectual disability, Wolff type 3068 short stature-endocrine defect

Intellectual disability-autism- syndrome 5 Cases Intellectual disability-obesity- 529965 speech apraxia-craniofacial 2 Cases 352530 brain malformations-facial dysmorphism syndrome Intellectual disability-balding- dysmorphism syndrome 3 Cases Intellectual disability-obesity- 3041 patella luxation-acromicria 2 Cases 397973 prognathism-eye and skin syndrome Intellectual disability- anomalies syndrome 4 Cases Intellectual disability- 364577 brachydactyly-Pierre Robin 2 Cases 3082 polydactyly-uncombable hair syndrome Intellectual disability-cardiac syndrome 18 Cases Intellectual disability-seizures- 508498 anomalies-short stature-joint 15 Cases 513456 abnormal gait-facial laxity syndrome Intellectual disability-cataracts- dysmorphism syndrome 13 Cases Intellectual disability-seizures- 3042 calcified pinnae-myopathy 4 Cases 369837 hypophosphatasia-ophthalmic- syndrome Intellectual disability-cataracts- 3 Cases skeletal anomalies syndrome 171860 Intellectual disability-seizures- 7 Cases kyphosis syndrome 369950 Intellectual disability-coarse macrocephaly-obesity syndrome 30 Cases Intellectual disability-severe 397709 face-macrocephaly-cerebellar 48 Cases 391372 speech delay-mild dysmorphism hypotrophy syndrome Intellectual disability-craniofacial syndrome 2 Cases 329224 dysmorphism-cryptorchidism Intellectual disability-short 6 Cases 3074 syndrome stature-hypertelorism syndrome Intellectual disability- 5 Intellectual disability-sparse hair- 61 Cases 3051 3454 developmental delay- Families brachydactyly syndrome Intellectual disability-spasticity- 3 Cases contractures syndrome 1891 Intellectual disability- ectrodactyly syndrome 4 Cases 3044 dysmorphism-hypogonadism- Intellectual disability-strabismus 34 Cases 363528 diabetes mellitus syndrome syndrome 100 Intellectual disability-epilepsy- 3 Cases 468620 981 Internal carotid absence Cases extrapyramidal syndrome Intellectual disability-expressive 13 Cases 436151 aphasia-facial dysmorphism Interstitial granulomatous 53 Cases 79099 syndrome dermatitis with arthritis Intellectual disability-facial 5.4 I* 7 Cases 182095 Interstitial lung disease 404440 dysmorphism syndrome due to

SETD5 haploinsufficiency Intestinal obstruction in the 16 Cases Intellectual disability-facial 314376 newborn due to guanylate 3 Cases 370010 dysmorphism-hand anomalies cyclase 2C deficiency

syndrome Intractable diarrhea-choanal 3 Cases 137622 369847 Intellectual disability- 5 Cases atresia-eye anomalies syndrome

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 49 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Intraductal papillary mucinous 0.011 I* with normal sweat glands 424058 carcinoma of pancreas 8 Isolated hereditary congenital Intrauterine growth restriction- 306527 Families 15 Cases facial paralysis 436144 short stature-early adult-onset

diabetes syndrome 13 Cases 542657 Isolated hyperchlorhidrosis Inverse Klippel-Trénaunay 15 Cases 329324 syndrome Isolated neonatal sclerosing 4 Cases 480556 150 cholangitis

84142 Isaac syndrome Cases 3.0 BP 35098 Isolated plagiocephaly

Isolated Dandy-Walker 1.0 BP* 1.0 P* 217 2924 Isolated polycystic liver disease malformation Isolated Dandy-Walker 2.1 P* Isolated sedoheptulokinase 2 Cases 217 440713 malformation deficiency 2.0 P* 18.6 BP* 2345 Isolated Klippel-Feil syndrome 823 Isolated spina bifida

0.6 BP* 145 2345 Isolated Klippel-Feil syndrome 457083 Isolated splenogonadal fusion Cases

5.0 BP* 718 Isolated Pierre Robin syndrome Isolated split hand-split foot 5.4 BP* 2440 0.3 P malformation 229717 Isolated agammaglobulinemia Isolated succinate-CoQ reductase 37 Cases 3208 Isolated 35.0 BP* deficiency 1048 anencephaly/exencephaly Isolated sulfite oxidase 50 Cases 99731 1.31 I* deficiency 250923 Isolated aniridia Isolated tracheoesophageal 2.2 BP 454750 20.0 BP fistula 557 Isolated anorectal malformation 6.7 BP* 3366 Isolated trigonocephaly 24.0 BP* 557 Isolated anorectal malformation 6 Cases 2306 Isotretinoin-like syndrome Isolated anterior cervical 20 Cases 3387 hypertrichosis 1.0 P* 33 Isovaleric acidemia 20 Cases 1134 Isolated arrhinia 200

Isolated autosomal dominant 1540 Jackson-Weiss syndrome Cases 21 Cases 199326 hypomagnesemia, Glaudemans

type 49 Cases 1873 Jalili syndrome 2.9 BP* 30391 Isolated biliary atresia 0.65 I* 79139 Japanese encephalitis 18.5 BP 30391 Isolated biliary atresia 4 Cases 313795 Jawad syndrome 120 Isolated cloverleaf skull 2343 Cases Jervell and Lange-Nielsen 0.3 P syndrome 90647 syndrome 50 Cases 1.4 BP* 79143 Isolated congenital anonychia 474 Jeune syndrome

15 Cases 0.4 BP* 88620 Isolated congenital anosmia 2315 Johanson-Blizzard syndrome

30 Cases 1.125 BP 91396 Isolated cryptophthalmia 475 Joubert syndrome

90 Cases Joubert syndrome and related 1.1 BP 1885 Isolated ectopia lentis 140874 disorders 2.4 BP* Joubert syndrome with Jeune 8 Cases 93928 Isolated epispadias 397715 asphyxiating thoracic dystrophy Isolated focal non-epidermolytic 2 Cases Joubert syndrome with hepatic 8 Cases 448264 1454 palmoplantar keratoderma defect 468666 Isolated generalized anhidrosis 7 Cases 2318 Joubert syndrome with 17 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 50 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families oculorenal defect 3.1 P* 2322 Kabuki syndrome 13 Cases 2319 Juberg-Hayward syndrome 84 Cases 254519 Kagami-Ogata syndrome 16 Cases 93972 Juberg-Marsidi syndrome Kagami-Ogata syndrome due to 7 Cases Junctional epidermolysis bullosa 9 Cases 254534 maternal 14q32.2 79405 inversa hypermethylation Junctional epidermolysis bullosa Kagami-Ogata syndrome due to 8 Cases 3 Cases 254528 306504 with respiratory and renal maternal 14q32.2 microdeletion

involvement Kagami-Ogata syndrome due to 37 Cases Junctional epidermolysis bullosa, 0.17 BP 96334 paternal uniparental disomy of 79404 generalized severe chromosome 14 100 3.75 P* Junctional epidermolysis bullosa- 478 Kallmann syndrome 79403 Cases pyloric atresia syndrome Kallmann syndrome-heart 8 Cases 2326 2 Cases disease syndrome 2321 Jung syndrome 0.34 I* 33276 Kaposi sarcoma 0.04 I* 248111 Juvenile Huntington disease 2.11 33276 Kaposi sarcoma 0.6 P* 248111 Juvenile Huntington disease 6 Cases 2328 Kapur-Toriello syndrome 50 Cases 2801 Juvenile Paget disease 11 Cases 2329 Karsch-Neugebauer syndrome 7.5 I* 1941 Juvenile absence epilepsy 12 Karyomegalic interstitial Juvenile cataract-microcornea- 12 Cases 401996 Families 247794 nephritis renal glucosuria syndrome 300 0.295 I 93672 Juvenile dermatomyositis 2330 Kasabach-Merritt syndrome Cases

70 Cases 2028 Juvenile hyaline fibromatosis 2.0 P* 480 Kearns-Sayre syndrome 1.5 I* 92 Juvenile idiopathic arthritis 12 Cases 2662 Keipert syndrome Juvenile myelomonocytic 0.1 P* 86834 65 Cases leukemia 2333 Kenny-Caffey syndrome 11 Cases 79076 Juvenile polyposis of infancy 3 Cases 435628 Keppen-Lubinsky syndrome 3.85 I* 2929 Juvenile polyposis syndrome Keratoderma hereditarium 50 Cases 494 4 Cases mutilans 247604 Juvenile primary lateral sclerosis Keratoderma hereditarium 50 Cases 79395 20 Cases mutilans with ichthyosis 26137 Juvenile temporal arteritis Keratosis follicularis-dwarfism- 6 Cases 2339 Juvenile-onset diabetes mellitus- cerebral atrophy syndrome 5 Cases 445062 central and peripheral Keratosis palmaris et plantaris- 20 Cases 86919 neurodegeneration syndrome clinodactyly syndrome 100 Ketamine-induced biliary 2 Cases 293807 2332 KBG syndrome Cases dilatation

Ketoacidosis due to 9 Cases 11 438075 monocarboxylate transporter-1 KCNQ2-related epileptic 439218 Families deficiency encephalopathy 30 Cases 85202 Keutel syndrome 100

477 KID syndrome Cases 1052

50918 Kikuchi-Fujimoto disease Cases

KLHL9-related early-onset distal 10 Cases 399081 myopathy 300 482 Kimura disease Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 51 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

2908 Kindler syndrome Cases 28 Cases 99812 LIG4 syndrome

18 Cases LIMS2-related limb-girdle 2 Cases 99741 King-Denborough syndrome 466801 muscular dystrophy 114 LIPE-related familial partial 4 Cases 435660 261494 Kleefstra syndrome Cases lipodystrophy

LMNA-related cardiocutaneous 5 Cases 363618 Kleefstra syndrome due to 9q34 86 Cases progeria syndrome 96147 microdeletion 50 Cases 2407 LOC syndrome Kleefstra syndrome due to a 23 Cases 261652 point mutation 54 Cases 83628 LUMBAR syndrome Klippel-Feil anomaly-myopathy- 2 Cases 447974 facial dysmorphism syndrome 100 Lacrimoauriculodentodigital 0.007 P* 2363 Cases 90308 Klippel-Trénaunay syndrome syndrome

Koolen-De Vries syndrome due 4 Cases 300 363965 to a point mutation 501 Lafora disease Cases

45 Cases 99749 Kostmann syndrome 25 Cases 530983 Lamb-Shaffer syndrome 8 Cases 2351 Kousseff syndrome 4 Cases 1296 Lambert syndrome 1.0 P* 487 Krabbe disease Lambert-Eaton myasthenic 1.0 P* 43393 1.0 BP* syndrome 487 Krabbe disease Lambert-Eaton myasthenic 0.35 P 43393 0.7 BP syndrome 487 Krabbe disease 0.55 P* 313 Lamellar ichthyosis 16 Cases 306674 Kufor-Rakeb syndrome Laminin subunit alpha 2-related 0.3 P* 258 2700 congenital muscular dystrophy

454745 Kuru Cases 100

2632 Langer mesomelic dysplasia Cases

1149 Kuskokwim syndrome Families 1.5 P* 389 Langerhans cell histiocytosis

Kyphoscoliosis-lateral tongue Large congenital melanocytic 2.75 P* 12 Cases 626 496689 atrophy-hereditary spastic nevus

paraplegia syndrome 0.3 P* 633 Laron syndrome Kyphoscoliotic Ehlers-Danlos 9 Cases 300179 syndrome due to FKBP22 Laron syndrome with 10 Cases 220465 deficiency immunodeficiency Kyphoscoliotic Ehlers-Danlos 1.0 BP 0.4 BP* 1900 syndrome due to lysyl 503 Larsen syndrome

hydroxylase 1 deficiency Larsen-like osseous dysplasia- 3 Cases Kyphosis-lateral tongue atrophy- 3 Cases 2370 496686 short stature syndrome myofibrillar myopathy syndrome Larsen-like syndrome, B3GAT3 14 Cases 140 284139 type 79314 L-2-hydroxyglutaric aciduria Cases 9 Cases 2808 Laryngeal abductor paralysis

L-Arginine:glycine 9 Cases Laryngeal abductor paralysis- 20 Cases 35704 2375 amidinotransferase deficiency intellectual disability syndrome 2 Cases 7.5 BP* 440731 L-ferritin deficiency 2004 Laryngotracheoesophageal cleft

LAMA5-related multisystemic 11 Cases Laryngotracheoesophageal cleft 30 Cases 521450 93940 syndrome type 3 650 LCAT deficiency 125

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 52 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Laryngotracheoesophageal cleft 20 Cases 2 Cases 93941 2347 Lethal Kniest-like dysplasia type 4 Late-onset distal myopathy, 11 Cases 8 Cases 98912 2371 Lethal Larsen-like syndrome Markesbery-Griggs type 5 Cases Lethal acantholytic epidermolysis 4 Cases 228227 Late-onset focal dermal elastosis 158687 bullosa Late-onset junctional 37 Cases Lethal arteriopathy syndrome 22 Cases 79406 314718 epidermolysis bullosa due to fibulin-4 deficiency Late-onset localized junctional 4 2 Cases Lethal ataxia with deafness and 231556 epidermolysis bullosa- 1187 Families optic atrophy intellectual disability syndrome 14 Cases Lethal congenital contracture 1 Family 2789 Lateral meningocele syndrome 137776 syndrome type 2 4 Cases Lethal congenital contracture 14 Cases 46059 Lathosterolosis 137783 syndrome type 3 14 Cases 3 Cases 2378 Laurin-Sandrow syndrome 1972 Lethal faciocardiomelic dysplasia

2.3 P* Lethal fetal brain malformation- 330015 Lead poisoning 4 Cases 444069 duodenal atresia-bilateral renal

2.5 BP hypoplasia syndrome 65 Leber congenital amaurosis Lethal fetal 2 Cases 2.5 P 439897 cerebrorenogenitourinary 65 Leber congenital amaurosis agenesis/hypoplasia syndrome Leber hereditary optic 4.3 P Lethal hemolytic anemia-genital 2 Cases 104 1046 neuropathy anomalies syndrome Leber hereditary optic 2.3 P* Lethal hydranencephaly- 2 Cases 104 480528 neuropathy diaphragmatic hernia syndrome 0.04 P* Lethal intrauterine growth 99718 Leber plus disease restriction-cortical 4 Cases 2570 1.4 I* malformation-congenital 549 Legionellosis contractures syndrome 2.2 BP Lethal left ventricular non- 137605 Legius syndrome compaction-seizures-hypotonia- 4 Cases 478049 2.8 BP* cataract-developmental delay 506 Leigh syndrome syndrome 28 2.0 P* Lethal multiple pterygium 506 Leigh syndrome 33108 Families syndrome

0.1 P* 507 Leishmaniasis Lethal neonatal spasticity- 8 Cases 435845 epileptic encephalopathy 25.0 I 507 Leishmaniasis syndrome

Lethal occipital encephalocele- 5 Cases 9 Cases 293925 140936 Lelis syndrome skeletal dysplasia syndrome

Lethal omphalocele-cleft palate 5 Cases 10.0 I* 2736 137839 Lemierre syndrome syndrome

Lethal osteosclerotic bone 40 Cases 0.1 I* 1832 2382 Lennox-Gastaut syndrome dysplasia

Lethal polymalformative 10 Cases 15.0 P* 210144 2382 Lennox-Gastaut syndrome syndrome, Boissel type

Lethal recessive 4 Cases Lenz-Majewski hyperostotic 10 Cases 1423 2658 chondrodysplasia dwarfism 350 3.7 I 548 Leprosy 2968 Leukocyte adhesion deficiency Cases

0.12 I* 509 Leptospirosis Leukocyte adhesion deficiency 0.1 P* 99842 type I 0.34 BP* 510 Lesch-Nyhan syndrome Leukocyte adhesion deficiency 7 Cases 99843 type II

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 53 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Leukocyte adhesion deficiency 40 Cases Limbic encephalitis with 5 Cases 99844 498700 type III neurexin-3 antibodies Leukoencephalopathy with 200 29 Cases 139444 bilateral anterior temporal lobe 220407 Limited systemic sclerosis Cases

cysts Leukoencephalopathy with brain 30 Cases 127 140933 Linear atrophoderma of Moulin stem and spinal cord 137898 Cases involvement-high lactate 30 Cases 228236 Linear focal elastosis syndrome Leukoencephalopathy with 50 Cases Lipodystrophy due to peptidic 1 Family 542310 1979 calcifications and cysts growth factors deficiency Leukoencephalopathy with mild 6 Cases Lipodystrophy-intellectual 3 Cases 363540 cerebellar ataxia and white 50811 disability-deafness syndrome matter edema 3 Cases Leukoencephalopathy-dystonia- 2 Cases 401859 Lipoic acid synthetase deficiency 163684 motor neuropathy syndrome 500 Leukoencephalopathy- 4 Cases 530 Lipoid proteinosis Cases 2386 palmoplantar keratoderma

syndrome 150 Leukoencephalopathy- 11 Cases 329481 Lipoprotein glomerulopathy Cases 83629 spondyloepimetaphyseal

dysplasia syndrome 1.0 I* Leukoencephalopathy-thalamus 69078 Liposarcoma 14 Cases 314051 and brainstem anomalies-high 4 Cases 401862 Lipoyl transferase 1 deficiency lactate syndrome Leukomelanoderma-infantilism- 36 Cases intellectual disability- 4 Cases 98955 Lisch epithelial corneal dystrophy 1816 hypodontia-hypotrichosis Lissencephaly due to TUBA1A 15 Cases 171680 syndrome mutation Leukonychia totalis-acanthosis- Lissencephaly type 3-familial 11 Cases 5 Cases 210133 nigricans-like lesions-abnormal 86821 fetal akinesia sequence

hair syndrome syndrome 0.9 P* Lissencephaly type 3-metacarpal 2 Cases 48162 Lewis-Sumner syndrome 86822 bone dysplasia syndrome 220 Lissencephaly with cerebellar 50 Cases 65285 Lhermitte-Duclos disease Cases 100012 hypoplasia type B

Lissencephaly with cerebellar 2 Cases 300 100013 hypoplasia type C 525 Lichen planopilaris Cases 0.43 I* 533 Listeriosis

100 0.337 I 254478 Lichen planus pemphigoides Cases 533 Listeriosis

Localized junctional 2 Cases 20 Cases 2390 Lichtenstein syndrome 251393 epidermolysis bullosa, non-

Herlitz type 72 Localized lichen myxedematosus 526 Liddle syndrome Families 10 Cases 90398 with mixed features of different

subtypes 2.32 P 263 Limb-girdle muscular dystrophy Localized lichen myxedematosus 5 Cases 90399 with monoclonal gammopathy or Limb-girdle muscular dystrophy 2 Cases 445110 systemic symptoms due to POMK deficiency 33 Cases 38 Cases 2406 Locked-in syndrome 69085 Limb-mammary syndrome

20.0 P* 60030 Loeys-Dietz syndrome Families 171673 Limbal stem cell deficiency

Limbic encephalitis with DPP6 4 Cases Long chain 3-hydroxyacyl-CoA 1.0 BP* 329341 5 antibodies dehydrogenase deficiency

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 54 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Long chain 3-hydroxyacyl-CoA 8.0 P* 5 dehydrogenase deficiency 0.6 P* 550 MELAS 1 Family 2408 Lowe-Kohn-Cohen syndrome 24 Cases 401973 MEND syndrome Lower limb malformation- 2 Cases 2487 hypospadias syndrome 7 Cases 508093 MEPAN syndrome Lower motor neuron syndrome 55 Cases 276435 with late-adult onset MFF-related encephalopathy due 4 Cases 12 Cases 485421 to mitochondrial and 844 Lown-Ganong-Levine syndrome peroxisomal fission defect 3 Cases 13 Cases 2409 Lowry-MacLean syndrome 79329 MGAT2-CDG

8 Cases 19 Cases 1824 Lowry-Wood syndrome 494433 MIRAGE syndrome

Lung agenesis-heart defect- 9 Cases MITF-related melanoma and 30 1120 thumb anomalies syndrome 293822 renal cell carcinoma Families

Lung fibrosis-immunodeficiency- predisposition syndrome 2 Cases 137631 46,XX gonadal dysgenesis MME-related autosomal 19 Cases syndrome 497757 dominant Charcot Marie Tooth

250 disease type 2

90283 Lupus erythematosus tumidus Cases 3 Cases 79330 MOGS-CDG

177.5 I* 8 Cases 91546 Lyme disease 2563 MOMO syndrome

21.9 I 8 Cases 91546 Lyme disease 79323 MPDU1-CDG

0.0135 I 25 Cases 538 Lymphangioleiomyomatosis 79319 MPI-CDG

0.25 P* 7 Cases 538 Lymphangioleiomyomatosis 263347 MRCS syndrome

0.15 P MSH3-related attenuated 4 Cases 538 Lymphangioleiomyomatosis 480536 familial adenomatous polyposis Lymphedema-atrial septal 5 Cases MT-ATP6-related mitochondrial 5 Cases 86915 320360 defects-facial changes syndrome spastic paraplegia Lymphedema-cerebral MYBPC1-related autosomal 5 Cases 86914 arteriovenous anomaly recessive non-lethal 4 Cases 498693 syndrome arthrogryposis multiplex Lymphedema-posterior choanal 6 Cases congenita syndrome 99141 atresia syndrome MYH7-related late-onset 12 Cases 2.0 P* 437572 scapuloperoneal muscular 275761 Lysosomal acid lipase deficiency dystrophy MAGEL2-related Prader-Willi-like 28 Cases 0.3 P* 398069 182050 MYH9-related disease syndrome 21 Cases MYO5B-related progressive 5 Cases 324972 MAGIC syndrome 480491 familial intrahepatic cholestasis 0.3 I* Macrocephaly-developmental 9 Cases 52417 MALT lymphoma 397612 delay syndrome 4.0 P* Macrocephaly-intellectual 40 Cases 52417 MALT lymphoma 210548 disability-autism syndrome Macrocephaly-intellectual 25 Cases 6 Cases 397941 MAN1B1-CDG 466791 disability-left ventricular non

5 compaction syndrome Macrocephaly-intellectual 171851 MEDNIK syndrome Families 8 Cases 457485 disability-neurodevelopmental

67 Cases disorder-small thorax syndrome 352328 MEGDEL syndrome Macrocephaly-short stature- 2 Cases 2427 85282 MEHMO syndrome 8 Cases paraplegia syndrome 2432 Macrosomia-microphthalmia- 5 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 55 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families cleft palate syndrome tumor of the ovary Macrostomia-preauricular tags- Malignant non-epithelial tumor 0.43 I* 9 Cases 398940 83619 external ophthalmoplegia of ovary

syndrome Malignant peripheral nerve 1.0 I 3148 Macrothrombocytopenia with 2 Cases sheath tumor 220448 mitral valve insufficiency Malignant sex cord stromal 1.85 P* 35808 Macrothrombocytopenia- tumor of ovary lymphedema-developmental 2 Cases Malignant sex cord stromal 0.13 I* 487796 35808 delay-facial dysmorphism- tumor of ovary camptodactyly syndrome 0.07 I* Macular coloboma-cleft palate- 2 Cases 398987 Malignant teratoma of ovary 91494 hallux valgus syndrome 170 200 252212 Malignant triton tumor Cases 137867 Madras motor neuron disease Cases

Malignant tumor of fallopian 1.0 P* 250 180242 tubes 163634 Maffucci syndrome Cases 1.075 I* 398043 Malignant tumor of penis

4 34 Cases 77297 Majeed syndrome Families 943 Malonic aciduria

11 Cases 1.0 P 238744 Mammary-digital-nail syndrome 87503 Mal de Meleda Mandibular hypoplasia-deafness- 21 Cases 20 Cases 363649 progeroid features-lipodystrophy 420179 Malan overgrowth syndrome syndrome 73.0 I 40 Cases 673 Malaria 2457 Mandibuloacral dysplasia

1.2 I* Mandibulofacial dysostosis with 4 Cases 673 Malaria 443995 alopecia 3.0 P* Mandibulofacial dysostosis- 673 Malaria 2 Cases 357158 macroblepharon-macrostomia

Male hypergonadotropic syndrome hypogonadism-intellectual 2 Cases 107 2234 Mandibulofacial dysostosis- disability-skeletal anomalies 79113 Cases microcephaly syndrome syndrome Maligant granulosa cell tumor of 0.12 I* 3.5 P* 99915 52416 Mantle cell lymphoma the ovary 200 0.67 BP 679 Malignant atrophic papulosis Cases 511 Maple syrup urine disease

500

Malignant dysgerminomatous 0.04 I* 99826 Marburg hemorrhagic fever Cases 99912 germ cell tumor of the ovary Malignant epithelial tumor of 9.39 I* 250 398934 ovary 221074 Marchiafava-Bignami disease Cases Malignant epithelial tumor of 0.73 I* 276145 salivary glands 50 Cases Malignant germ cell tumor of 0.08 I* 2461 Marden-Walker syndrome 35807 ovary 25.0 I* Malignant germ cell tumor of 2.3 558 Marfan syndrome 35807 ovary 20.0 P* Malignant melanoma of the 0.26 I* 558 Marfan syndrome 168999 mucosa 15.0 P Malignant melanoma of the 1.5 558 Marfan syndrome 168999 mucosa Marfanoid habitus-autosomal 114 4 Cases Malignant migrating focal 2463 recessive intellectual disability 293181 Cases seizures of infancy syndrome Marfanoid habitus-inguinal 2 Cases 314041 213512 Malignant mixed Müllerian 0.12 I* hernia-advanced bone age

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 56 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families syndrome Marfanoid syndrome, De Silva 6 Cases 2.6 BP* 2464 564 Meckel syndrome type 7.0 P* 2.44 P* 300912 Marginal zone lymphoma 70588 Meconium aspiration syndrome

0.3 I* Medial condensing osteitis of the 58 Cases 300912 Marginal zone lymphoma 57196 clavicle 200 70 Cases 2006 Median cleft lip/mandibule 559 Marinesco-Sjögren syndrome Cases

17 Cases 2699 Median nodule of the upper lip Families 560 Marshall syndrome

33 Cases 3 Cases 561 Marshall-Smith syndrome 370127 Medich giant platelet syndrome

Martinique crinkled retinal 14 Cases Medium chain acyl-CoA 12.0 BP* 466718 42 pigment epitheliopathy dehydrogenase deficiency 3.0 P* Medium chain acyl-CoA 6.85 P 98292 Mastocytosis 42 dehydrogenase deficiency 10.0 P 5.0 P* 98292 Mastocytosis 1332 Medullary thyroid carcinoma

10.0 I* 0.22 I* 2209 Maternal phenylketonuria 1332 Medullary thyroid carcinoma

2 Cases 0.11 I* 411712 Maternal riboflavin deficiency 616 Medulloblastoma

Maternal uniparental disomy of 3 Cases 1.0 P* 97678 616 Medulloblastoma chromosome 13 Maternal uniparental disomy of 12 Cases 250 96186 chromosome 20 98954 Meesmann corneal dystrophy Cases

Maternal uniparental disomy of 2 Cases 96187 chromosome 21 Megaconial congenital muscular 19 Cases 280671 Maternal uniparental disomy of 4 Cases dystrophy 96188 chromosome 22 230 Megacystis-microcolon-intestinal Maternal uniparental disomy of 15 Cases 2241 Cases 96181 hypoperistalsis syndrome chromosome 6 Megalencephalic 100 Maternally-inherited diabetes 0.1 P* 225 2478 leukoencephalopathy with Cases and deafness 43 Cases subcortical cysts 2470 Matthew-Wood syndrome Megalencephaly-capillary 170

Mayer-Rokitansky-Küster-Hauser 11.0 BP 60040 malformation-polymicrogyria Cases 3109 syndrome syndrome Megalencephaly-polymicrogyria- Mayer-Rokitansky-Küster-Hauser 1.0 BP* 62 Cases 2578 83473 postaxial polydactyly- syndrome type 2 54 Cases hydrocephalus syndrome 57782 Mazabraud syndrome Megalencephaly-severe 2 Cases 0.55 P* 457359 kyphoscoliosis-overgrowth 562 McCune-Albright syndrome syndrome 2 2 Cases 2482 Melhem-Fahl syndrome 2471 McDonough syndrome Families 70 Cases 2484 Melnick-Needles syndrome 90 Cases 2473 McKusick-Kaufman syndrome 0.09 P* 2485 Melorheostosis 100 McLeod neuroacanthocytosis 5 59306 Cases Melorheostosis with syndrome 1879 Families osteopoikilosis 13 Cases 3097 Meacham syndrome Mendelian susceptibility to 31 Cases 99898 mycobacterial diseases due to 564 Meckel syndrome 4.0 BP complete IFNgammaR1

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 57 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families deficiency hypoplasia-brachydacty Families Mendelian susceptibility to syndrome mycobacterial diseases due to 13 Cases Metaplastic carcinoma of the 0.06 I* 319547 213531 complete IFNgammaR2 breast deficiency 81 Cases 2635 Metatropic dysplasia Mendelian susceptibility to 49 Cases 319558 mycobacterial diseases due to 0.2 BP* 2635 Metatropic dysplasia complete IL12B deficiency Mendelian susceptibility to 180 40 Cases 319552 mycobacterial diseases due to Cases 1923 Methimazole embryofetopathy

complete IL12RB1 deficiency 3.0 P* Mendelian susceptibility to 565782 Methotrexate toxicity 6 Cases 319563 mycobacterial diseases due to Methylcobalamin deficiency type 27 Cases 2169 complete ISG15 deficiency cblE Mendelian susceptibility to 2 Cases Methylcobalamin deficiency type 33 Cases 319600 mycobacterial diseases due to 2170 cblG partial IRF8 deficiency Methylmalonic acidemia due to Mendelian susceptibility to 7 Cases 17 Cases 308425 methylmalonyl-CoA epimerase 319595 mycobacterial diseases due to deficiency partial STAT1 deficiency 500 Methylmalonic acidemia with 0.15 I* 26 Cases 2495 Meningioma homocystinuria

1.75 Methylmalonic acidemia with 15 Cases 2495 Meningioma 79284 homocystinuria type cblF 0.33 BP* 500 565 Menkes disease Methylmalonic acidemia with 79282 Cases Menstrual cycle-dependent 5 Cases homocystinuria, type cblC 498251 periodic fever Methylmalonic acidemia with 17 Cases 6 79283 Mesoaxial synostotic syndactyly homocystinuria, type cblD 157801 Families Methylmalonic acidemia with 2 Cases with phalangeal reduction 369955 homocystinuria, type cblJ 5 Cases Methylmalonic acidemia with 18 Cases 2496 Mesomelia-synostoses syndrome 369962 homocystinuria, type cblX Mesomelic dwarfism-cleft 2 Cases Methylmalonic aciduria due to 5 Cases 2631 280183 palate-camptodactyly syndrome transcobalamin receptor defect 5 Mesomelic dysplasia, Kantaputra Metopic ridging-ptosis-facial 8 Cases 1836 Families 502430 type dysmorphism syndrome 300

25 Cases 309025 Mevalonate kinase deficiency Cases 2499 Metachondromatosis

1.47 BP* 30 Cases 512 Metachromatic leukodystrophy 29 Mevalonic aciduria

0.1 P* 203 512 Metachromatic leukodystrophy 2510 Micro syndrome Cases Metaphyseal 4 Cases 1240 acroscyphodysplasia Microbrachycephaly-ptosis-cleft 2 Cases 27 Cases 2511 1040 Metaphyseal anadysplasia lip syndrome Microcephalic osteodysplastic 4 Cases Metaphyseal chondrodysplasia, 16 Cases 85172 33067 dysplasia, Saul-Wilson type Jansen type 150 Microcephalic osteodysplastic Metaphyseal chondrodysplasia, 2 Cases 2637 Cases 166038 primordial dwarfism type II Kaitila type Metaphyseal chondrodysplasia, 18 Cases Microcephalic osteodysplastic 2501 30 Cases Spahr type 2636 primordial dwarfism types I and

Metaphyseal dysostosis- III 3 Cases 2502 intellectual disability-conductive Microcephalic primordial 12 Cases 468631 deafness syndrome dwarfism due to RTTN deficiency 2504 Metaphyseal dysplasia-maxillary 2 329228 Microcephalic primordial 10 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 58 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families dwarfism due to ZNF335 disability-sensorineural hearing deficiency loss-epilepsy-abnormal muscle Microcephalic primordial 2 Cases tone syndrome 319675 dwarfism, Dauber type 50 Microcephaly-lymphedema- Microcephalic primordial 3 Cases 2526 Families 2617 chorioretinopathy syndrome dwarfism, Montreal type Microcephalic primordial 2 Cases Microcephaly-microcornea 2 Cases 2643 2528 dwarfism, Toriello type syndrome, Seemanova type Microcephalic primordial Microcephaly-micromelia 32 Cases 2 Cases 572768 436182 dwarfism-insulin resistance syndrome

syndrome Microcephaly-polymicrogyria- 4 Cases Microcephaly-albinism-digital 2 Cases 171703 corpus callosum agenesis 2513 anomalies syndrome syndrome Microcephaly-seizures- Microcephaly-brachydactyly- 3 Cases 2 Cases 3433 2519 intellectual disability-heart kyphoscoliosis syndrome Microcephaly-brain defect- disease syndrome 3 Cases Microcephaly-short stature- 2523 spasticity-hypernatremia 2 Cases 423306 intellectual disability-facial syndrome Microcephaly-capillary 10 Cases dysmorphism syndrome 294016 Microcephaly-short stature-limb 29 Cases malformation syndrome 572773 Microcephaly-cardiac defect-lung 3 Cases abnormalities syndrome 2516 Microcephaly-thin corpus malsegmentation syndrome 4 Cases Microcephaly-cardiomyopathy 3 Cases 397951 callosum-intellectual disability 2515 syndrome syndrome Microcephaly-cerebellar Microcornea-glaucoma-absent 5 Cases 4 Cases 2536 329332 hypoplasia-cardiac conduction frontal sinuses syndrome Microcornea-myopic defect syndrome 14 Cases Microcephaly-cervical spine 2 Cases 369970 chorioretinal atrophy- 2522 fusion anomalies syndrome telecanthus syndrome Microcephaly-cleft palate- Microcornea-posterior 3 Cases 2521 abnormal retinal pigmentation megalolenticonus-persistent 8 Cases 231736 syndrome fetal vasculature-coloboma Microcephaly-complex motor syndrome 3 Cases 423894 and sensory axonal neuropathy Microcytic anemia with liver iron 3 Cases 83642 syndrome overload Microcephaly-congenital Microduplication Xp11.22p11.23 12 Cases 5 Cases 217377 488168 cataract-psoriasiform dermatitis syndrome Microgastria-limb reduction 16 Cases syndrome 2538 Microcephaly-corpus callosum defect syndrome and cerebellar vermis 4 Cases Micrognathia-recurrent 500159 infections-behavioral 4 Cases hypoplasia-facial dysmorphism- 476126 intellectual disability syndrom abnormalities-mild intellectual Microcephaly-corpus callosum disability syndrome 5 Cases 457284 hypoplasia-intellectual disability- Microlissencephaly-micromelia 2 Cases 50810 facial dysmorphism syndrome syndrome 2 Microcephaly-deafness- 2 Cases Microphthalmia with brain and 2533 139471 Families intellectual disability syndrome digit anomalies Microcephaly-facial 35 dysmorphism-ocular anomalies- 10 Cases Microphthalmia with limb 521445 1106 Families multiple congenital anomalies anomalies syndrome Microcephaly-facio-cardio- Microphthalmia with linear skin 55 Cases 5 Cases 2556 217026 skeletal syndrome, defects syndrome

Hadziselimovic type Microphthalmia-anophthalmia- 8.3 BP* 98555 Microcephaly- coloboma 2 Cases 2172 glomerulonephritis-marfanoid Microphthalmia-brain atrophy 3 Cases 77299 habitus syndrome syndrome 457351 Microcephaly-intellectual 14 Cases 2547 Microphthalmia-microtia-fetal 2 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 59 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families akinesia syndrome Microphthalmia-retinitis Mitochondrial hypertrophic 9 Cases 8 Cases 251279 pigmentosa-foveoschisis-optic 314637 cardiomyopathy with lactic

disc drusen syndrome acidosis due to MTO1 deficiency 1.0 I* Mitochondrial membrane 727 Microscopic polyangiitis 0.1 P 289560 protein-associated

13.0 BP* neurodegeneration 83463 Microtia Mitochondrial myopathy and 7 Cases 2598 15.5 BP sideroblastic anemia 83463 Microtia Mitochondrial myopathy- 9 Cases Microtia-eye coloboma- 502423 cerebellar ataxia-pigmentary 1 Family 139450 imperforation of the retinopathy syndrome

nasolacrimal duct syndrome Mitochondrial myopathy-lactic 2 Cases 2597 2 Cases acidosis-deafness syndrome 289522 Microtriplication 11q24.1 Mitochondrial 0.1 P* 137 298 neurogastrointestinal

2290 Microvillus inclusion disease Cases encephalomyopathy

Mitochondrial oxidative 9.0 P* 9 Cases 2443 phosphorylation disorder due to 2557 Mietens syndrome nuclear DNA anomalies 5 Cases Mitochondrial pyruvate carrier 4 Cases 2558 Mikati-Najjar-Sahli syndrome 447784 deficiency 100 0.6 P* Mitochondrial trifunctional 169799 Mild hemophilia B 746 Cases protein deficiency Mild spondyloepiphyseal 4 dysplasia due to COL2A1 Mitochondrial trifunctional 1.0 P* 93279 Families 746 mutation with early-onset protein deficiency

osteoarthritis 0.01 I* 180234 Mixed germ cell tumor 0.1 I* 98919 Miller Fisher syndrome Mixed sclerosing bone dystrophy 2 Cases 1.0 BP* 324364 with extra-skeletal 531 Miller-Dieker syndrome manifestations Minimal pigment 10 Cases Moderate and severe traumatic 37.8 P* 352734 90056 oculocutaneous albinism type 1 brain injury Mirror polydactyly-vertebral 0.6 P* 0.3 P* 169796 Moderately severe hemophilia B 3004 segmentation-limbs defects

syndrome 300

570 Moebius syndrome Cases Mitochondrial DNA depletion syndrome, encephalomyopathic 2 Cases 1933 form with methylmalonic Moebius syndrome-axonal 7 Cases aciduria 2560 neuropathy-hypogonadotropic

Mitochondrial DNA depletion hypogonadism syndrome 5 Cases 255235 syndrome, encephalomyopathic 91 Cases 52368 Mohr-Tranebjaerg syndrome form with renal tubulopathy Mitochondrial DNA depletion Monocytopenia with 22 Cases 228423 syndrome, encephalomyopathic 20 Cases susceptibility to infections 369897 form with variable craniofacial Mononen-Karnes-Senac 1 Family 2565 anomalies syndrome Mitochondrial DNA depletion 100 2.0 BP* 279934 syndrome, hepatocerebral form Cases 1598 Monosomy 18p

due to DGUOK deficiency 2.5 BP Mitochondrial DNA depletion 1600 Monosomy 18q 3 Cases 363534 syndrome, hepatocerebrorenal 50 Cases 574 Monosomy 21 form Mitochondrial DNA depletion 45 Cases 200 254875 syndrome, myopathic form 48652 Monosomy 22q13.3 Cases Mitochondrial DNA-related 2 1349 cardiomyopathy and hearing loss Families 77301 Monosomy 9q22.3 42 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 60 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

60 Cases 0.5 P* 83467 Morvan syndrome 579 Mucopolysaccharidosis type 1

Mosaic genome-wide paternal 13 Cases 0.7 BP* 329813 580 Mucopolysaccharidosis type 2 uniparental disomy 1 Case 0.68 BP 1692 Mosaic trisomy 1 580 Mucopolysaccharidosis type 2

226 0.2 P* 580 Mucopolysaccharidosis type 2 1708 Mosaic trisomy 16 Cases

Mucopolysaccharidosis type 2, 0.4 BP* 217085 31 Cases severe form 1711 Mosaic trisomy 17 0.87 BP* 581 Mucopolysaccharidosis type 3 22 Cases 1723 Mosaic trisomy 2 0.3 P* 581 Mucopolysaccharidosis type 3 6 Cases 100071 Mosaic trisomy 3 15.0 P* 309297 Mucopolysaccharidosis type 4A 31 Cases 1747 Mosaic trisomy 7 0.16 BP* 583 Mucopolysaccharidosis type 6 3.0 I* 96061 Mosaic trisomy 8 0.16 P* 583 Mucopolysaccharidosis type 6 50 Cases 99776 Mosaic trisomy 9 0.01 P* 584 Mucopolysaccharidosis type 7 Mosaic variegated aneuploidy 41 Cases 1052 syndrome Mucopolysaccharidosis-like 300 syndrome with congenital heart 19 Cases 505248 3347 Mounier-Kühn syndrome Cases defects and hematopoietic

disorders 1.7 BP* 277 2152 Mowat-Wilson syndrome 566943 Mueller-Weiss syndrome Cases

Moyamoya angiopathy-short stature-facial dysmorphism- 9 Cases 3.33 BP 280679 53271 Muenke syndrome hypergonadotropic hypogonadism syndrome 205

0.035 I* 587 Muir-Torre syndrome Cases 2573 Moyamoya disease

Moyamoya disease with early- 9 Cases 150 401945 onset achalasia 2576 Mulibrey nanism Cases

26 Cases 2574 Moynahan syndrome Multicentric osteolysis- 50 Cases 371428 35 Cases nodulosis-arthropathy spectrum 100024 Mu-heavy chain disease 200

Mucinous adenocarcinoma of 0.85 I* 139436 Multicentric reticulohistiocytosis Cases 398961 ovary Mucinous cystadenocarcinoma 0.007 I* 23.26 BP 424053 1851 Multicystic dysplastic kidney of the pancreas 200 0.67 BP 3282 Multifocal atrial tachycardia 575 Muckle-Wells syndrome Cases

1.5 P 641 Multifocal motor neuropathy 0.84 BP* 576 Mucolipidosis type II Multinodular goiter-cystic 3 Cases 2091 1.0 BP* kidney-polydactyly syndrome 577 Mucolipidosis type III Multinucleated neurons- 13.0 P anhydramnios-renal dysplasia- 3 Cases 423461 Mucolipidosis type III alpha/beta 500135 cerebellar hypoplasia- 1.0 BP* hydranencephaly syndrome 579 Mucopolysaccharidosis type 1 Multiple congenital anomalies- 15 Cases 280633 579 Mucopolysaccharidosis type 1 0.82 BP hypotonia-seizures syndrome 300496 Multiple congenital anomalies- 24 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 61 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families hypotonia-seizures syndrome type 2 1.8 I 102 Multiple system atrophy Multiple endocrine neoplasia 3.3 P* 652 type 1 3.5 P 102 Multiple system atrophy Multiple endocrine neoplasia 2.9 P* 653 type 2 Multiple system atrophy, 2.4 P* 98933 5.0 P* parkinsonian type 251 Multiple epiphyseal dysplasia Multisystemic smooth muscle 7 Cases 404463 18 dysfunction syndrome Multiple epiphyseal dysplasia 93311 Families Muscle-eye-brain disease with type 5 2 Cases 370997 bilateral multicystic

Multiple epiphyseal dysplasia, 4 Cases leucodystrophy 166024 Al-Gazali type Muscular atrophy-ataxia-retinitis 12 Cases Multiple epiphyseal dysplasia, 1 Family 2579 pigmentosa-diabetes mellitus 166011 Beighton type syndrome Multiple epiphyseal dysplasia, 2 Cases 12 Cases 166016 199340 Muscular dystrophy, Selcen type Lowry type Multiple epiphyseal dysplasia, 2 Cases Muscular hypertrophy- 166032 2 Cases with miniepiphyses 324416 hepatomegaly-polyhydramnios

Multiple epiphyseal dysplasia, syndrome 3 Cases 166029 with severe proximal femoral Musculocontractural Ehlers- 34 Cases 2953 dysplasia Danlos syndrome Multiple mitochondrial 21 Cases Mutilating hereditary sensory 401869 14 Cases dysfunctions syndrome type 1 139578 neuropathy with spastic

Multiple mitochondrial 6 Cases paraplegia 401874 dysfunctions syndrome type 2 Mutilating palmoplantar 73 Cases Multiple mitochondrial 2 Cases 659 keratoderma with periorificial 363424 dysfunctions syndrome type 3 keratotic plaques Multiple mitochondrial 8 Cases 1.7 I* 457406 589 Myasthenia gravis dysfunctions syndrome type 4 Multiple mitochondrial 6 Cases 7.77 P 569274 589 Myasthenia gravis dysfunctions syndrome type 5 Multiple mitochondrial 5 Cases 20.0 P* 569290 589 Myasthenia gravis dysfunctions syndrome type 6 6.0 I 0.53 I 29073 Multiple myeloma 589 Myasthenia gravis

2.4 I* Mycophenolate mofetil 25 Cases 29073 Multiple myeloma 268249 embryopathy 11.9 P* 0.59 I* 29073 Multiple myeloma 178566 Mycosis fungoides and variants

3.0 P* 1.5 I* 321 Multiple osteochondromas 52688 Myelodysplastic syndrome

Multiple paragangliomas 2 Cases 5.02 324299 52688 Myelodysplastic syndrome associated with polycythemia Multiple pterygium-malignant 4 Cases Myelodysplastic/myeloproliferati 0.29 I* 2215 98275 hyperthermia syndrome ve disease Multiple sclerosis-ichthyosis- 2 Cases 0.02 I* 3151 86850 Myeloid sarcoma factor VIII deficiency syndrome 100 3.07 I* Multiple self-healing squamous 98274 Myeloproliferative neoplasm 65748 Cases epithelioma 55 Cases 2588 Myhre syndrome 50 Cases 585 Multiple sulfatase deficiency 106

30 86909 Myoclonic epilepsy of infancy Cases

3237 Multiple synostoses syndrome Families

Myoclonus-cerebellar ataxia- 4 Cases 2589 102 Multiple system atrophy 3.7 P* deafness syndrome

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 62 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Myopathic Ehlers-Danlos 8 Cases 1 Family 536516 2663 Nathalie syndrome syndrome 6.7 P 49 Cases 206647 Myotonic dystrophy 255229 Navajo neurohepatopathy

8.78 P* 45.0 P 206647 Myotonic dystrophy 391673 Necrotizing enterocolitis

0.1 I* 2.0 BP* 99967 Myxoid/round cell liposarcoma 607 Nemaline myopathy

Müllerian derivatives- Neonatal acute respiratory 0.067 BP 8 Cases 217563 1655 lymphangiectasia-polydactyly distress due to SP-B deficiency

syndrome Neonatal antiphospholipid 34 Cases 398097 Müllerian duct anomalies-limb 5 Cases syndrome 2491 anomalies syndrome Neonatal autoimmune hemolytic 2 Cases 398109 3 Cases anemia 2608 N syndrome 3 Cases 398117 Neonatal dermatomyositis NAD(P)HX dehydratase 6 Cases 555402 deficiency 1.1 BP* 224 Neonatal diabetes mellitus 11 Cases 555407 NAD(P)HX epimerase deficiency Neonatal diabetes-congenital NDE1-related 1 Family hypothyroidism-congenital 3 Cases 443162 79118 microhydranencephaly glaucoma-hepatic fibrosis- NEK9-related lethal skeletal 5 Cases polycystic kidneys syndrome 464366 dysplasia Neonatal encephalomyopathy- 11 Cases 2 Cases 457185 cardiomyopathy-respiratory 447731 NIK deficiency distress syndrome Neonatal epileptic 8 Cases 4 Cases 263665 NK-cell enteropathy 557064 encephalopathy due to

NKX6-2-related autosomal glutaminase deficiency 25 Cases 527497 recessive hypomyelinating 35 Cases 446 Neonatal hemochromatosis leukodystrophy NLRP12-associated hereditary 19 Cases Neonatal ichthyosis-sclerosing 12 Cases 247868 59303 periodic fever syndrome cholangitis syndrome NPHP3-related Meckel-like 10 Cases Neonatal inflammatory skin and 3 Cases 3032 294023 syndrome bowel disease Naegeli-Franceschetti-Jadassohn 0.035 P* 6 Cases 69087 398127 Neonatal scleroderma syndrome 100 Neonatal severe

245 Nager syndrome Cases cardiopulmonary failure due to 3 Cases 466784 mitochondrial methylation Nail and teeth abnormalities- defect marginal palmoplantar 6 Cases 24.4 P* 423454 94058 Neovascular glaucoma keratoderma-oral hyperpigmentation syndrome 0.14 I* 654 Nephroblastoma 0.2 BP* 2614 Nail-patella syndrome 10.0 BP* 654 Nephroblastoma 3 Cases 2613 Nail-patella-like renal disease 3.65 654 Nephroblastoma 196

627 Nance-Horan syndrome Cases 0.15 P* 223 Nephrogenic diabetes insipidus

25.0 P* Nephrogenic diabetes insipidus- 2073 Narcolepsy type 1 2 Cases 3145 intracranial calcification-facial

Nasopalpebral lipoma-coloboma 30 Cases dysmorphism syndrome 2399 syndrome Nephrogenic syndrome of 21 Cases 93606 2.0 P* inappropriate antidiuresis 150 Nasopharyngeal carcinoma Nephropathy-deafness- 5 Cases 2668 0.36 I* hyperparathyroidism syndrome 150 Nasopharyngeal carcinoma 2669 Nephrosis-deafness-urinary 5 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 63 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families tract-digital malformations stomach syndrome 3 Cases 2673 Neurofaciodigitorenal syndrome Nephrotic syndrome-deafness- 3 Cases 300333 pretibial epidermolysis bullosa 90 Cases 157846 Neuroferritinopathy syndrome Nestor-Guillermo progeria 2 Cases 21.3 P* 280576 636 Neurofibromatosis type 1 syndrome 0.5 BP* 33.3 BP 634 Netherton syndrome 636 Neurofibromatosis type 1

0.5 P* 1.7 P* 634 Netherton syndrome 637 Neurofibromatosis type 2

91 Cases Neurogenic arthrogryposis 4.3 BP* 2671 Neu-Laxova syndrome 1143 multiplex congenita Neuhauser-Eichner-Opitz 5 Cases Neurogenic scapuloperoneal 15 Cases 2672 85146 syndrome syndrome, Kaeser type 91.05 BP* Neurological conditions 3388 Neural tube defect 15 Cases 137754 associated with aminoacylase 1

11.0 P* deficiency 635 Neuroblastoma Neurometabolic disorder due to 30 Cases 35705 1.26 I serine deficiency 635 Neuroblastoma Neuromyelitis optica spectrum 1.5 P* 71211 5.8 BP* disorder 635 Neuroblastoma 2.0 P* 216 Neuronal ceroid lipofuscinosis 1.25 P* 2481 Neurocutaneous melanocytosis Neuropathy with hearing 1 Family 139512 Neurodegeneration due to 3- impairment 20 Cases 88639 hydroxyisobutyryl-CoA hydrolase 4.2 P* 137596 Neurotrophic keratopathy deficiency Neurodegeneration with brain 0.2 P* 50 Cases 385 165 Neutral lipid storage disease iron accumulation Neurodegenerative syndrome 3 Cases 36 Cases 217382 due to cerebral folate transport 98908 Neutral lipid storage myopathy

deficiency Neutropenia-monocytopenia- 3 Cases 2690 Neurodevelopmental delay- deafness syndrome seizures-ophthalmic anomalies- 10 Cases Neutrophil immunodeficiency 2 Cases 529665 183707 osteopenia-cerebellar atrophy syndrome syndrome 1.17 P* 263432 Nevus of Ito Neurodevelopmental disorder- craniofacial dysmorphism- 25 Cases 0.25 BP* 453499 77292 Niemann-Pick disease type A cardiac defect-skeletal anomalies syndrome 0.4 P* 77293 Niemann-Pick disease type B Neurodevelopmental disorder- craniofacial dysmorphism- 2 Cases 1.0 P* 352665 cardiac defect-skeletal anomalies 646 Niemann-Pick disease type C

syndrome due to 9q21.3 Night blindness-skeletal microdeletion 2 Cases 1390 anomalies-dysmorphism Neurodevelopmental disorder- syndrome craniofacial dysmorphism- 10 Cases 1.0 BP 453504 cardiac defect-skeletal anomalies 647 Nijmegen breakage syndrome

syndrome due to a point Nijmegen breakage syndrome- 1 Case mutation 240760 like disorder Neuroectodermal 20 Cases 33445 556 melanolysosomal disease 99825 Nipah virus disease Cases 2.53 I* 877 Neuroendocrine neoplasm

Nodal marginal zone B-cell 1.0 P* Neuroendocrine tumor of 0.21 I* 86867 97253 lymphoma pancreas 86893 Nodular lymphocyte 0.12 I 100075 Neuroendocrine tumor of 3.2 P*

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 64 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families predominant Hodgkin lymphoma Obesity due to prohormone 16 Cases 71528 Nodular lymphocyte 0.095 I* convertase I deficiency 86893 predominant Hodgkin lymphoma Obesity-colitis-hypothyroidism- 2 Cases 11.6 I* 88643 cardiac hypertrophy- 547 Non-Hodgkin lymphoma developmental delay syndrome Non-acquired combined pituitary 29.0 BP* 20 Cases 467 198 Occipital horn syndrome hormone deficiency Occipital pachygyria and 3 Cases Non-acquired combined pituitary 280640 hormone deficiency- 13 Cases polymicrogyria 231720 sensorineural hearing loss-spine 100

abnormalities syndrome 2704 Ochoa syndrome Cases

Non-epidermolytic palmoplantar 2.5 P* 2337 keratoderma 3 Ocular albinism with congenital Non-eruption of teeth-maxillary 352740 Families 4 Cases sensorineural deafness 2972 hypoplasia-genu valgum

syndrome Ocular albinism with late-onset 9 Cases 1000 Non-functioning pituitary 1.05 I sensorineural deafness 91349 adenoma Ocular anomalies-axonal 8 Cases Non-functioning pituitary 2.55 I* 496790 neuropathy-developmental delay 91349 adenoma syndrome 0.038 I* Ocular motor apraxia, Cogan 50 Cases 357034 Non-hereditary retinoblastoma 1125 type Non-hypoproteinemic 1 Family 5 Cases 329883 2714 Oculo-palato-cerebral syndrome hypertrophic gastropathy 42.0 BP Oculoauricular syndrome, 5 Cases 363999 Non-immune hydrops fetalis 157962 Schorderet type 18.0 P* Oculoauriculofrontonasal 41 Cases 90061 Non-infectious posterior uveitis 398156 syndrome Non-papillary transitional cell 37.0 P* Oculocerebral hypopigmentation 14 Cases 209989 2719 carcinoma of the bladder syndrome, Cross type Non-progressive cerebellar 15 Cases Oculocerebral hypopigmentation 2 Cases 314647 2720 ataxia with intellectual disability syndrome, Preus type Non-seminomatous germ cell 1.21 I* Oculocerebrocutaneous 38 Cases 363494 1647 tumor of testis syndrome Non-seminomatous germ cell 33.53 5 Cases 363494 557003 Oculocerebrodental syndrome tumor of testis Non-spherocytic hemolytic 17 Oculocerebrofacial syndrome, 14 Cases 2707 90031 anemia due to hexokinase Families Kaufman type

deficiency Oculocerebrorenal syndrome of 0.2 P 534 296 Lowe Noonan syndrome with multiple 500 Cases Oculocerebrorenal syndrome of 0.2 P* lentigines 534 Lowe Noonan syndrome-like disorder 27 Cases 5.9 P 2701 55 Oculocutaneous albinism with loose anagen hair 400 2.5 P 352731 Oculocutaneous albinism type 1 649 Norrie disease Cases

1.3 P 79431 Oculocutaneous albinism type 1A 2 North Carolina macular 75327 Families 1.3 P dystrophy 79434 Oculocutaneous albinism type 1B

3 Cases 2.55 P 2760 OSLAM syndrome 79432 Oculocutaneous albinism type 2

15 Cases 1.0 P 397615 Obesity due to CEP19 deficiency 79435 Oculocutaneous albinism type 4

Obesity due to congenital leptin 30 Cases 1 Family 66628 370091 Oculocutaneous albinism type 5 deficiency Obesity due to pro- 7 Cases 71526 370097 Oculocutaneous albinism type 6 1 Case opiomelanocortin deficiency

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 65 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 7 Cases 2920 Oliver syndrome 9 Cases 352745 Oculocutaneous albinism type 7 1.0 P* 296 Ollier disease Oculodental syndrome, 1 Family 2709 Rutherfurd type 25 Cases 39041 Omenn syndrome 243

2710 Oculodentodigital dysplasia Cases 30 Cases 2733 Omodysplasia

Oculogastrointestinal muscular 1 Family 11.7 BP* 1876 660 Omphalocele dystrophy 4 Cases Omphalocele syndrome, 5 Cases 1794 Oculomaxillofacial dysostosis 3164 Shprintzen-Goldberg type 3 Cases Omphalocele-diaphragmatic 2713 Oculoosteocutaneous syndrome 7 Cases 496693 hernia-cardiovascular anomalies-

1 Family radial ray defect syndrome 99806 Oculootodental syndrome 400

20 Cases 352540 Oncogenic osteomalacia Cases 2717 Oculotrichoanal syndrome

2 Cases 5 Cases 2718 Oculotrichodysplasia 300504 Onychocytic matricoma

Odonto-onycho dysplasia- 2 Cases 50 Cases 2722 300512 Onychomatricoma alopecia syndrome 30 Cases Ophthalmomandibulomelic 3 Cases 2721 Odonto-onycho-dermal dysplasia 2741 dysplasia Ophthalmoplegia-intellectual Odonto-tricho-ungual-digito- 21 Cases 6 Cases 69082 2743 disability-lingua scrotalis palmar syndrome 11 Cases syndrome 166272 Odontochondrodysplasia 3.0 P* 2745 Opitz G/BBB syndrome 4 Cases 77295 Odontoleukodystrophy 30 Cases 2746 Opsismodysplasia Odontomatosis-aortae 3 Cases 2724 Opsoclonus-myoclonus 0.02 I* esophagus stenosis syndrome 1183 5 Cases syndrome 1811 Odontomicronychial dysplasia Optic atrophy-ataxia-peripheral 17 Cases 4 Cases 543470 neuropathy-global 2723 Odontotrichomelic syndrome developmental delay syndrome Off-periods in Parkinson disease 4.15 P* Optic atrophy-intellectual 6 Cases 391655 401777 not responding to oral treatment disability syndrome 8 Cases Optic nerve edema- 3 Cases 276432 Ogden syndrome 313800 splenomegaly syndrome 50 Cases 0.12 I 75382 Oguchi disease 2086 Optic pathway glioma

Oral-facial-digital syndrome with 5 Cases 3 Cases 2729 Okamoto syndrome 508501 short stature and

Oligoarticular juvenile idiopathic 20.5 P* brachymesophalangy 85410 26 Cases arthritis 52994 Orbital leiomyoma 0.11 I* 251651 Oligoastrocytic tumor Ornithine transcarbamylase 1.0 P* 664 14 Cases deficiency 75378 Oligocone trichromacy Ornithine transcarbamylase 1.77 BP 664 0.35 I* deficiency 46484 Oligodendroglial tumor 1.2 BP* 2750 Orofaciodigital syndrome type 1 0.25 I* 251627 Oligodendroglioma 1 Case 141327 Orofaciodigital syndrome type 12 2 Oligodontia-cancer 300576 Families 1 Case predisposition syndrome 141330 Orofaciodigital syndrome type 13

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 66 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

434179 Orofaciodigital syndrome type 14 Families Osteopetrosis- 8 Cases 178389 hypogammaglobulinemia

20 Cases syndrome 2751 Orofaciodigital syndrome type 2 Osteoporosis-oculocutaneous 1 Case 2786 5 Cases hypopigmentation syndrome 2752 Orofaciodigital syndrome type 3 Osteoporosis-pseudoglioma 0.05 P* 2788 29 Cases syndrome 2753 Orofaciodigital syndrome type 4 0.23 I* 668 Osteosarcoma 12 Cases 2919 Orofaciodigital syndrome type 5 3.17 668 Osteosarcoma 2

2754 Orofaciodigital syndrome type 6 Families Osteosclerosis-developmental 13 Cases 178377 delay-craniosynostosis syndrome 20 Cases Osteosclerosis-ichthyosis- 2755 Orofaciodigital syndrome type 8 3 Cases 75325 premature ovarian failure

10 Cases syndrome 141007 Orofaciodigital syndrome type 9 Osteosclerotic metaphyseal 7 Cases 500548 Ossification anomalies- dysplasia 2 Cases 73230 psychomotor developmental 10

delay syndrome 2791 Otodental syndrome Families

35.0 P* 2764 Osteochondritis dissecans 6 Cases 2793 Otoonychoperoneal syndrome Osteochondrodysplatic nanism- 2 Cases 2653 deafness-retinitis pigmentosa Otopalatodigital syndrome type 40 Cases 90652 syndrome 2 Osteoclastic giant cell tumor of 0.001 I* Otospondylomegaepiphyseal 30 Cases 424080 1427 pancreas dysplasia 30 Cases 49.0 P* 2763 Osteocraniostenosis 213500 Ovarian cancer

10.0 P* 17 Cases 666 Osteogenesis imperfecta 99853 Ovarioleukodystrophy

0.4 BP* Overgrowth syndrome with 2q37 4 Cases 216804 Osteogenesis imperfecta type 2 498488 translocation 47 Cases 6 216828 Osteogenesis imperfecta type 5 Overgrowth-macrocephaly-facial 137634 Families dysmorphism syndrome Osteogenesis imperfecta- 2 Cases 2773 retinopathy-seizures-intellectual Overgrowth-metaphyseal 4 Cases disability syndrome 498485 undermodeling-spondylar

7 Cases dysplasia syndrome 2645 Osteoglosphonic dysplasia 20 Overhydrated hereditary 35 Cases 3203 Families 2777 Osteomesopyknosis stomatocytosis

100 6 Cases Osteopathia striata-cranial 991 PAGOD syndrome 2780 Cases sclerosis syndrome 2 Cases 2825 PARC syndrome Osteopathia striata-pigmentary 3 Cases 2779 dermopathy-white forelock PCNA-related progressive 4 Cases syndrome 438134 neurodegenerative

Osteopenia-intellectual 2 Cases photosensitivity syndrome 2324 disability-sparse hair syndrome PDE4D haploinsufficiency 7 Cases 439822 Osteopenia-myopia-hearing loss- syndrome 2 Cases 91133 intellectual disability-facial 10 Cases 99807 PEHO-like syndrome dysmorphism syndrome Osteopetrosis and related 1.0 I* 13 Cases 2781 313936 PENS syndrome disorders Osteopetrosis with renal tubular 100 500 2785 42642 PFAPA syndrome acidosis Cases Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 67 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Cases 46 Cases 319646 PGM1-CDG 4 Cases 1952 Pacman dysplasia 20 Cases 443811 PGM3-CDG 0.51 I* 180275 Paget disease of the nipple 300

42775 PHACE syndrome Cases 67 Cases 1993 Pai syndrome

2 Cases Painful orbital and systemic 2876 PHAVER syndrome 4 Cases 300501 neurofibromas-marfanoid

PIEZO1-related generalized habitus syndrome 10 Cases 568062 lymphatic dysplasia with non- Palatal anomalies-widely spaced 3 Cases immune hydrops fetalis 477993 teeth-facial dysmorphism-

PLAA-associated 15 Cases developmental delay syndrome 521426 neurodevelopmental disorder 100

PLCG2-associated antibody 3 672 Pallister-Hall syndrome Cases

300359 deficiency and immune Families

dysregulation Palmoplantar keratoderma, 40 Cases 140966 105 Nagashima type PLG-related hereditary 537072 Cases Palmoplantar keratoderma-XX angioedema with normal C1Inh sex reversal-predisposition to 5 Cases 85112 PLIN1-related familial partial 3 Cases squamous cell carcinoma 280356 lipodystrophy syndrome 10 PMP2-related Charcot-Marie- 13 Cases Palmoplantar keratoderma- 476394 2202 Families Tooth disease type 1 deafness syndrome PMP22-RAI1 contiguous gene 23 Cases 477817 10 duplication syndrome Palmoplantar keratoderma- POGLUT1-related limb-girdle 4 Cases 2198 Families 480682 esophageal carcinoma syndrome muscular dystrophy R21 Palmoplantar keratoderma- POMGNT1-related limb-girdle 2 Cases 23 Cases 206564 538574 hereditary motor and sensory muscular dystrophy R15 POMGNT2-related limb-girdle 3 Cases neuropathy syndrome 565899 Palmoplantar keratoderma- 1 Family muscular dystrophy R24 2201 POMT2-related limb-girdle 1 Case spastic paralysis syndrome 206559 Pancreatic agenesis- 4 Cases muscular dystrophy R14 556955 PPARG-related familial partial 10 Cases holoprosencephaly syndrome 79083 2 Cases lipodystrophy 309108 Pancreatic colipase deficiency PRKAR1B-related 12 Cases Pancreatic hypoplasia-diabetes- 412066 neurodegenerative dementia 10 Cases 2255 congenital heart disease with intermediate filaments PRUNE1-related neurological 48 Cases syndrome 544469 Pancreatic insufficiency-anemia- 5 Cases syndrome 199337 PURA-related severe neonatal hyperostosis syndrome 24 Cases 438213 hypotonia-seizures- 60 Cases 677 Pancreatoblastoma encephalopathy syndrome Pancytopenia due to IKZF1 39 Cases PURA-related severe neonatal 317473 hypotonia-seizures- 24 Cases mutations 438216 Pancytopenia-developmental 3 Cases encephalopathy syndrome due 401764 to a point mutation delay syndrome PYCR2-related microcephaly- Pantothenate kinase-associated 0.15 P* 18 Cases 157850 481152 progressive neurodegeneration

leukoencephalopathy 0.14 I* 319298 Papillary renal cell carcinoma 204

2796 Pachydermoperiostosis Cases 0.25 P 678 Papillon-Lefèvre syndrome

Pachygyria-intellectual disability- 5 Cases 8 Cases 2798 2812 Parana hard skin syndrome epilepsy syndrome 2309 Pachyonychia congenita 1000 63455 Paraneoplastic pemphigus 60 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 68 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Patterson-Stevenson-Fontaine 7 Cases 2439 Paraplegia-intellectual disability- 6 Cases syndrome 2824 hyperkeratosis syndrome 95 Cases 699 Pearson syndrome 0.01 363478 Paratesticular adenocarcinoma Pectus excavatum- 1 Family 0.02 I* 2835 macrocephaly-dysplastic nails 143 Parathyroid carcinoma syndrome 0.28 24 Cases 143 Parathyroid carcinoma 487809 Pediatric collagenous gastritis

Parietal foramina with clavicular 8 Cases Pediatric hepatocellular 0.15 I* 251290 33402 hypoplasia carcinoma 40 Paris-Trousseau 50 Cases 851 263548 Peeling skin syndrome type A Families thrombocytopenia Paroxysmal dystonic 20 Cases 30 53583 choreathetosis with episodic 263553 Peeling skin syndrome type B Families ataxia and spasticity Paroxysmal exertion-induced 50 Cases 98811 Peeling skin-leukonychia-acral dyskinesia 4 Cases 4 444138 punctate keratoses-cheilitis- Paroxysmal extreme pain 46348 Families knuckle pads syndrome disorder 0.25 P* 702 Pelizaeus-Merzbacher disease Paroxysmal kinesigenic 0.6 P 98809 Pelizaeus-Merzbacher disease, 0.17 P* dyskinesia 280219 Paroxysmal nocturnal 2.0 P* classic form 447 Pelizaeus-Merzbacher disease, 0.03 P* hemoglobinuria 280210 Paroxysmal non-kinesigenic 0.1 P connatal form 98810 Pelizaeus-Merzbacher disease, 0.03 P* dyskinesia 280224 Partial atrioventricular septal 20.0 BP* transitional form 1330 Pelvic dysplasia-arthrogryposis of 5 Cases defect 2840 Partial atrioventricular septal 30.0 P* lower limbs syndrome 1330 10 Cases defect 2839 Pelvis-shoulder dysplasia 20.8 P 1646 Partial chromosome Y deletion 4 Cases 93333 Pelviscapular dysplasia 20.0 P* 1646 Partial chromosome Y deletion 18.0 P* 704 Pemphigus vulgaris Partial corpus callosum agenesis- cerebellar vermis hypoplasia 2 Cases 7.0 P* 401959 705 Pendred syndrome with posterior fossa cysts syndrome 80 Cases 49 Penile agenesis Partial deep dermal and full 10.0 P* 90076 thickness burns 0.55 BP* 1335 Pentalogy of Cantrell Partial duplication of the long 50 Cases 262941 arm of chromosome 14 0.67 BP 1335 Pentalogy of Cantrell 50 Cases 2805 Partial pancreatic agenesis Pericardial and diaphragmatic 20 Cases 2847 2 defect

94083 Partington syndrome Families 50.0 I* 65250 Perineural cyst

5 Periodic fever-infantile 4 Cases 86789 Patella aplasia/hypoplasia Families 436166 enterocolitis-autoinflammatory

syndrome Patent ductus arteriosus- Periodic paralysis with later- 9 Cases 7 Cases 397750 228190 bicuspid aortic valve-hand onset distal motor neuropathy

anomalies syndrome Periodic paralysis with transient 4 Cases 397755 Paternal 20q13.2q13.3 2 Cases compartment-like syndrome 261304 microdeletion syndrome Periodontal Ehlers-Danlos 62 Cases 75392 Paternal uniparental disomy of 4 Cases syndrome 96192 chromosome 7

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 69 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 10 Cases Phocomelia-ectrodactyly- 139426 Perioral myoclonia with absences 4 Cases 2878 deafness-sinus arrhythmia

30.0 BP syndrome 563 Peripartum cardiomyopathy Phosphoenolpyruvate 10 Cases 2880 Peripheral demyelinating carboxykinase deficiency neuropathy-central 30 40 Cases Phosphoribosylpyrophosphate 163746 dysmyelinating leukodystrophy- 3222 Families synthetase superactivity Waardenburg syndrome- Hirschsprung disease 90 Cases 498228 Phyllodes tumor of the prostate 6 Cases 1795 Peripheral dysostosis Piebald trait-neurologic defects 8 Cases 2885 Peripheral motor neuropathy- 2 Cases syndrome 2400 dysautonomia syndrome 7 Cases 487825 Pierpont syndrome Peripheral neuropathy- 15 Cases 397744 myopathy-hoarseness-hearing Pierre Robin syndrome- 2 Cases 2888 loss syndrome faciodigital anomaly syndrome 150 40

168816 Peritoneal cystic mesothelioma Cases 2670 Pierson syndrome Families

30 Cases Pigmentation defects- 2849 Perlman syndrome 2 Cases 447961 palmoplantar keratoderma-skin

Permanent congenital 33.3 BP* carcinoma syndrome 226292 hypothyroidism 100 Pigmented paravenous Permanent neonatal diabetes 0.38 BP* 251295 Cases 99885 retinochoroidal atrophy mellitus Permanent neonatal diabetes 20.0 P* 4 Cases 66627 Pigmented villonodular synovitis 65288 mellitus-pancreatic and

cerebellar agenesis syndrome Pili torti-developmental delay- 2 Cases Peroxisomal acyl-CoA oxidase 40 Cases 2891 neurological abnormalities 2971 deficiency syndrome 61 Cases Pili torti-onychodysplasia 1 Family 2855 Perrault syndrome 2890 syndrome 53 Cases Pilodental dysplasia-refractive 2 Cases 178509 Perry syndrome 2892 errors syndrome 5 Cases 0.02 I* 97341 Persistent placoid maculopathy 251909 Pineoblastoma

154 105 Persistent polyclonal B-cell 300324 Cases 221150 Pitt-Hopkins-like syndrome Cases lymphocytosis

60 Cases 0.04 I* 708 Peters anomaly 300385 Pituitary carcinoma

100 0.87 300385 Pituitary carcinoma 709 Peters plus syndrome Cases

48 Cases 2897 Pityriasis rubra pilaris 2.2 BP 2869 Peutz-Jeghers syndrome 33.0 P 439167 Placental insufficiency 0.4 P* 2869 Peutz-Jeghers syndrome Placental site trophoblastic 0.02 I* 99928 1.0 BP* tumor 710 Pfeiffer syndrome Placental site trophoblastic 0.86 99928 2 Cases tumor 2871 Pfeiffer-Palm-Teller syndrome 2.2 I* 707 Plague Phakomatosis 34 Cases 2874 pigmentokeratotica 0.04 I* 454714 Plasma cell leukemia Phalangeal microgeodic 50 Cases 352636 syndrome Plectin-related limb-girdle 6 Cases 254361 10.0 BP* muscular dystrophy R17 716 Phenylketonuria 99969 Pleomorphic liposarcoma 0.05 I*

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 70 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families disability-acromicria-premature Pleomorphic salivary gland 2.725 I menopause syndrome 454821 adenoma Polysyndactyly-cardiac 8 Cases 2934 0.01 I* malformation syndrome 251607 Pleomorphic xanthoastrocytoma Polyvalvular heart disease 19 Cases 228410 13.0 P* syndrome 449266 Pleural empyema Pontine autosomal dominant 11 Cases 3.1 P* 477749 microangiopathy with 50251 Pleural mesothelioma leukoencephalopathy 1.9 I* 22 Cases 50251 Pleural mesothelioma 269229 Pontine tegmental cap dysplasia

40 0.5 BP* Pontocerebellar hypoplasia type 64742 Pleuropulmonary blastoma 2254 Families 1 Pleuropulmonary blastoma 0.007 I 284343 familial tumor susceptibility Pontocerebellar hypoplasia type 23 Cases 411493 syndrome 10 81 25 Cases Pontocerebellar hypoplasia type 54028 Plummer-Vinson syndrome 2524 Families 2 Pneumonia caused by 50.0 P* 3 90066 Pseudomonas aeruginosa Pontocerebellar hypoplasia type 97249 Families infection 3 50 Cases 221046 Poikiloderma with neutropenia 10 Pontocerebellar hypoplasia type 1.5 BP* 166063 Families 2911 Poland syndrome 4

3.0 P* Pontocerebellar hypoplasia type 3 Cases 767 Polyarteritis nodosa 166068 5 1.9 I* Pontocerebellar hypoplasia type 10 Cases 729 Polycythemia vera 166073 6 30.0 P* Pontocerebellar hypoplasia type 4 Cases 729 Polycythemia vera 284339 7 1 Family Pontocerebellar hypoplasia type 6 Cases 2917 Polydactyly-myopia syndrome 324569 8 Polyendocrine-polyneuropathy 3 Cases Pontocerebellar hypoplasia type 14 Cases 453533 369920 syndrome 9 Polyglucosan body myopathy 11 Cases 0.3 BP* 397937 294963 Popliteal pterygium syndrome type 1 Porencephaly-cerebellar Polyglucosan body myopathy 15 Cases 2 Cases 456369 2941 hypoplasia-internal type 2 Polyhydramnios- malformations syndrome 17 Cases Porencephaly-microcephaly- 500533 megalencephaly-symptomatic 8 Cases 306547 bilateral congenital cataract epilepsy syndrome Polymalformative genetic syndrome 10.0 P* 183422 syndrome with increased risk of Porokeratotic eccrine ostial and 45 Cases 166286 developing cancer dermal duct nevus Polymicrogyria due to TUBB2B 36 Cases 5.25 P 300573 738 Porphyria mutation Polymicrogyria with optic nerve 4 Cases 0.6 I* 250972 101330 Porphyria cutanea tarda hypoplasia 0.585 I* 4.0 P* 732 Polymyositis 101330 Porphyria cutanea tarda

7.1 P* 0.008 I* 732 Polymyositis 79473 Porphyria variegata

Polyneuropathy-hearing loss- 0.32 P* 19 Cases 79473 Porphyria variegata 171848 ataxia-retinitis pigmentosa- Port-wine nevi-mega cisterna 5 Cases cataract syndrome 2703 2928 Polyneuropathy-intellectual 3 Cases magna-hydrocephalus syndrome 70568 Post-transplant 26.2 P*

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 71 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families lymphoproliferative disease 40 Pretibial dystrophic 30 Cases 79410 Families 246 Postaxial acrofacial dysostosis epidermolysis bullosa

Postaxial polydactyly-anterior 112 6 Cases 169464 Primary CD59 deficiency 420584 pituitary anomalies-facial Cases

dysmorphism syndrome 48.99 P* 289390 Primary Sjögren syndrome Postaxial polydactyly-dental and 3 Cases 2916 vertebral anomalies syndrome 6.92 I 289390 Primary Sjögren syndrome 4 Cases 2730 Postaxial tetramelic oligodactyly 2.57 I* 186 Primary biliary cholangitis 11 Posterior amorphous corneal 98971 Families 3.0 I dystrophy 186 Primary biliary cholangitis

Posterior column ataxia-retinitis 20 Cases 21.05 P 88628 186 Primary biliary cholangitis pigmentosa syndrome Posterior fusion of lumbosacral 25.0 P* 3 Cases 186 Primary biliary cholangitis 2064 vertebrae-blepharoptosis

syndrome 5.0 BP* 244 Primary ciliary dyskinesia 20.0 BP* 95706 Posterior hypospadias Primary ciliary dyskinesia- 20 Cases 247522 2.0 P* retinitis pigmentosa syndrome 93110 Posterior urethral valve Primary congenital 37.5 P* 226295 4.125 BP* hypothyroidism 93110 Posterior urethral valve Primary cutaneous CD30+ T-cell 0.18 I* 541 Posterior-predominant lymphoproliferative disease lissencephaly-broad flat pons 8 Cases Primary cutaneous T-cell 5.2 I* 572013 171901 and medulla-midline crossing lymphoma defects syndrome Primary cutaneous T-cell 24.0 P* 171901 Postnatal microcephaly-infantile lymphoma hypotonia-spastic diplegia- 17 Cases 0.75 I* 477673 542 Primary cutaneous lymphoma dysarthria-intellectual disability syndrome 8 Cases 45 Cases 98807 Primary dystonia, DYT13 type 279947 Postorgasmic illness syndrome 3 Cases Postural orthostatic tachycardia 2 Cases 370103 Primary dystonia, DYT17 type 443236 syndrome due to NET deficiency 16 Cases 40 Cases 306734 Primary dystonia, DYT21 type 52022 Potocki-Shaffer syndrome 5 Cases 22.0 P* 464440 Primary dystonia, DYT27 type 217067 Pouchitis 22 Cases 16 Cases 98805 Primary dystonia, DYT4 type 397606 PrP systemic amyloidosis 53 Cases 3.1 BP* 98806 Primary dystonia, DYT6 type 739 Prader-Willi syndrome 200 117 48686 Primary effusion lymphoma Cases 398073 Prader-Willi-like syndrome Cases

Primary hepatic neuroendocrine 0.2 I 5 Cases 100085 293462 Pre-Descemet corneal dystrophy carcinoma Primary hyperaldosteronism- 2 Cases Preaxial polydactyly-colobomata- 2 Cases 369929 seizures-neurological 2921 intellectual disability syndrome abnormalities syndrome Predisposition to severe viral 1 Family Primary hypergonadotropic 574918 7 Cases infection due to IRF7 deficiency 2232 hypogonadism-partial alopecia 45.0 P* 275555 Preeclampsia syndrome 10 Cases Prenatal-onset spinal muscular 93599 Primary hyperoxaluria type 2 7 Cases 486811 atrophy with congenital bone 93600 Primary hyperoxaluria type 3 50 Cases fractures

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 72 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families lipodystrophy syndrome Primary hypomagnesemia with Progeroid features- 3 Cases 3 Cases 564178 refractory seizures and 435953 hepatocellular carcinoma

intellectual disability predisposition syndrome 100 1 Case Primary hypomagnesemia with 2963 Progeroid syndrome, Petty type 30924 Cases secondary hypocalcemia Progressive autosomal recessive 13 Cases 448251 Primary immunodeficiency ataxia-deafness syndrome 4 Cases 90023 syndrome due to LAMTOR2 2 Progressive bifocal chorioretinal deficiency 75373 Families atrophy Primary immunodeficiency with 4 Cases 75391 natural-killer cell deficiency and Progressive cavitating 19 Cases 139447 adrenal insufficiency leukoencephalopathy Primary immunodeficiency with 1 Case Progressive cerebello-cerebral 7 Cases 431166 post-measles-mumps-rubella 247198 atrophy vaccine viral infection Progressive encephalopathy with 2 Cases Primary intralymphatic 30 Cases 431361 leukodystrophy due to DECR 458768 angioendothelioma deficiency 1.5 P* 35689 Primary lateral sclerosis Progressive essential tremor- speech impairment-facial 5 Cases 16.7 P* 457212 dysmorphism-intellectual 77240 Primary lymphedema disability-abnormal behavior Primary mediastinal large B-cell 5.0 P* syndrome 98838 lymphoma Progressive external 6 Cases Primary membranoproliferative 16.0 P* 352447 ophthalmoplegia-myopathy- 54370 glomerulonephritis emaciation syndrome Primary microcephaly-epilepsy- Progressive familial intrahepatic 14 Cases 8 Cases 480483 306558 permanent neonatal diabetes cholestasis type 4

syndrome Progressive familial intrahepatic 4 Cases 480476 Primary microcephaly-mild cholestasis type 5 8 Cases 391408 intellectual disability-young- Progressive microcephaly- 9 Cases onset diabetes syndrome 477814 seizures-cortical blindness-

1.0 I* developmental delay syndrome 824 Primary myelofibrosis 9 Progressive myoclonic epilepsy 3.0 P* 263516 Families 824 Primary myelofibrosis type 3

390 Progressive myoclonic epilepsy 3 Cases 402082 238606 Primary orthostatic tremor Cases type 5

Progressive myoclonic epilepsy 12 Cases 280620 Primary pigmented nodular 0.04 P* type 6 189439 adrenocortical disease Progressive myoclonic epilepsy 13 Cases 435438 7.0 P type 7 95432 Primary progressive aphasia Progressive myoclonic epilepsy 4 Cases 424027 Primary progressive apraxia of 16 Cases type 8 314566 speech Progressive myoclonic epilepsy 2 Cases 457265 0.77 I* type 9 171 Primary sclerosing cholangitis Progressive myoclonic epilepsy 5 Cases 352596 8.1 P with dystonia 171 Primary sclerosing cholangitis 2.5 P* 100070 Progressive non-fluent aphasia 7.84 P* 171 Primary sclerosing cholangitis 0.7 I* 100070 Progressive non-fluent aphasia 0.65 I 171 Primary sclerosing cholangitis Progressive non-infectious 67 Cases 2062 30.0 P* anterior vertebral fusion 314701 Primary systemic amyloidosis Progressive polyneuropathy with 4 Cases 217396 Progeria-short stature- 11 Cases bilateral striatal necrosis 2959 pigmented nevi syndrome Progressive retinal dystrophy 5 Cases 352718 300382 Progeroid and marfanoid aspect- 7 Cases due to retinol transport defect

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 73 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Progressive 33 Cases 447977 scapulohumeroperoneal distal 11 Cases 221120 Pseudoaminopterin syndrome myopathy Progressive sensorineural 4 13 Cases 228012 hearing loss-hypertrophic Families 85174 Pseudodiastrophic dysplasia

cardiomyopathy syndrome 107

Progressive 756 Pseudohypoaldosteronism type 1 Cases spondyloepimetaphyseal 4 Cases 457395 dysplasia-short stature-short 180

fourth metatarsals-intellectual 757 Pseudohypoaldosteronism type 2 Cases

disability syndrome 0.65 I Pseudohypoaldosteronism type 24 Cases 683 Progressive supranuclear palsy 300525 2D 14.0 P* Pseudohypoaldosteronism type 17 Cases 683 Progressive supranuclear palsy 300530 2E 6.0 P Pseudoleprechaunism syndrome, 2 Cases 683 Progressive supranuclear palsy 2976 Patterson type Progressive supranuclear palsy- 0.6 P* 0.1 I 240103 26790 Pseudomyxoma peritonei corticobasal syndrome Progressive supranuclear palsy- 10 Cases 2.0 P* 240112 progressive non-fluent aphasia 26790 Pseudomyxoma peritonei

syndrome 2 Cases 90 Cases 2985 Pseudoprogeria syndrome 742 Prolidase deficiency 2.5 P* Prominent glabella- 758 Pseudoxanthoma elasticum 2 Cases 2083 microcephaly-hypogenitalism Pseudoxanthoma elasticum-like 13 Cases syndrome 436274 skin manifestations with retinitis 1.5 I 35 Propionic acidemia pigmentosa Pseudoxanthomatous diffuse 10 Cases 0.2 P* 280794 35 Propionic acidemia cutaneous mastocytosis Psoriasis-related juvenile 4.2 P* Proteasome-associated 40 Cases 85436 324977 idiopathic arthritis autoinflammatory syndrome Psychomotor regression- 6 Cases 0.01 I* 505242 oculomotor apraxia-movement 251598 Protoplasmic astrocytoma disorder-nephropathy syndrome Proximal 16p11.2 microdeletion 20.0 P* Pterin-4 alpha-carbinolamine 21 Cases 261197 1578 syndrome dehydratase deficiency Proximal myopathy with 15 Cases Pterygium colli-intellectual 401768 2 Cases extrapyramidal signs 2988 disability-digital anomalies Proximal myopathy with focal 4 Cases 521305 syndrome depletion of mitochondria Ptosis-strabismus-ectopic pupils 1 Family 1.0 P* 2999 606 Proximal myotonic myopathy syndrome Ptosis-upper ocular movement 3 Cases 2.6 I* 228396 limitation-absence of lacrimal 70 Proximal spinal muscular atrophy punctum syndrome 20.0 BP* Ptosis-vocal cord paralysis 2 Cases 70 Proximal spinal muscular atrophy 2997 syndrome Proximal spinal muscular atrophy 0.26 I* 2.0 P* 83330 182090 Pulmonary arterial hypertension type 1 Proximal spinal muscular atrophy 1.23 I* Pulmonary arterial hypertension 83418 0.57 P* type 2 275803 associated with congenital heart

Proximal spinal muscular atrophy 1.1 I* disease 83419 type 3 Pulmonary arterial hypertension 0.25 P* Proximal spinal muscular atrophy 0.32 I* 275798 associated with connective tissue 83420 type 4 disease 60 Cases Pulmonary arteriovenous 2.5 I 52530 Pseudo-von Willebrand disease 2038 malformation 750 Pseudoachondroplasia 3.3 P 64741 Pulmonary blastoma 350

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 74 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Cases RAS-associated autoimmune 20 Cases 268114 leukoproliferative disease 100 REN-related autosomal dominant 21 Cases Pulmonary capillary 217330 199241 Cases tubulointerstitial kidney disease hemangiomatosis RERE-related 10 Cases 494344 Pulmonary fibrosis-hepatic neurodevelopmental syndrome 4 Cases 210136 hyperplasia-bone marrow 8 Cases 244310 RFT1-CDG hypoplasia syndrome Pulmonary fungal infections in 22.0 P* 4 Cases 217080 140976 RHYNS syndrome patients deemed at risk Pulmonary non-tuberculous 6.0 P* 2 Cases 411703 420741 RIDDLE syndrome mycobacterial infection 0.015 I* 10 Cases 31837 Pulmonary venoocclusive disease 217335 RIN2 syndrome

Punctate acrokeratoderma 7 Cases RNF13-related severe early-onset 3 Cases 99710 544503 freckle-like pigmentation epileptic encephalopathy 35 Radial hypoplasia-triphalangeal Punctate palmoplantar 8 Cases 79501 Families 2252 thumbs-hypospadias-maxillary keratoderma type 1 diastema syndrome Punctate palmoplantar 13 Cases Radial ray hypoplasia-choanal 3 Cases 79502 3026 keratoderma type 2 atresia syndrome Pure hair and nail ectodermal 20 Cases 35.0 P* 69084 70475 Radiation proctitis dysplasia Purine nucleoside phosphorylase 72 Cases 4 Cases 760 3015 Radio-renal syndrome deficiency 0.13 P Radio-ulnar synostosis- 763 Pycnodysostosis 20 Cases 71289 amegakaryocytic

5 Cases thrombocytopenia syndrome 3003 Pyknoachondrogenesis Radioulnar synostosis- 4 Cases 30 Cases 3270 developmental delay-hypotonia 3005 Pyle disease syndrome 0.74 I Radioulnar synostosis- 13 Cases 48104 Pyoderma gangrenosum 3268 microcephaly-scoliosis syndrome Pyoderma gangrenosum-acne- 8 Cases 36 Cases 3019 Ramon syndrome 289478 suppurative hidradenitis

syndrome 6 Cases 1051 Ramos-Arroyo syndrome Pyogenic arthritis-pyoderma 53 Cases 69126 gangrenosum-acne syndrome Rapid-onset childhood obesity- Pyramidal molars-abnormal 8 Cases hypothalamic dysfunction- 96 Cases 2561 293987 upper lip syndrome hypoventilation-autonomic 0.2 BP* dysregulation syndrome 3006 Pyridoxine-dependent epilepsy 100 Rapid-onset dystonia- 0.4 BP* 71517 Cases 3008 Pyruvate carboxylase deficiency parkinsonism

Pyruvate carboxylase deficiency, 5 Cases Rare adenocarcinoma of the 3.55 I* 353320 213528 benign type breast Pyruvate dehydrogenase E3 20 Cases 11.79 I* 2394 217074 Rare carcinoma of pancreas deficiency 0.16 I* 15.5 P* 781 Q fever 217074 Rare carcinoma of pancreas

3 Cases 3.5 P 3010 Qazi-Markouizos syndrome 217074 Rare carcinoma of pancreas

20 Cases 8.3 3021 RAPADILINO syndrome 217074 Rare carcinoma of pancreas

RARS-related autosomal 3.9 I 4 Cases 217074 Rare carcinoma of pancreas 438114 recessive hypomyelinating

leukodystrophy Rare congenital non-syndromic 7.8 BP* 88991 heart malformation

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 75 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Rare cutaneous lupus 50.0 P* deafness syndrome 535 erythematosus 42.0 P* 217071 Renal cell carcinoma 18.6 I* 63443 Rare epithelial tumor of stomach 8.35 I* 217071 Renal cell carcinoma 49.17 63443 Rare epithelial tumor of stomach 180

12.5 P* 1475 Renal coloboma syndrome Cases 2415 Rare lymphatic malformation

0.13 I* 43.5 BP* 182114 Rare urogenital tumor 93108 Renal dysplasia

100 Renier-Gabreels-Jasper 5 Cases 93975 1929 Rasmussen subacute encephalitis Cases syndrome

64 Cases 3242 Renpenning syndrome 38 Cases 99852 Ravine syndrome Resistance to thyroid hormone 35 Cases 15.0 I* 566231 due to a mutation in thyroid 461 Recessive X-linked ichthyosis hormone receptor alpha 16.6 P* Resistance to thyrotropin- 2 Cases 461 Recessive X-linked ichthyosis 99832 releasing hormone syndrome 100 30 Cases Recessive dystrophic 1662 Restrictive dermopathy 79409 Cases epidermolysis bullosa inversa 0.03 I* 33355 Reticular dysgenesis Recessive intellectual disability- 12 Cases 280384 motor dysfunction-multiple joint 130 Reticulate acropigmentation of contractures syndrome 178307 Cases Kitamura Recurrent hepatitis C virus 7.0 P* 90052 induced liver disease in liver 32 Cases 458763 Retiform hemangioendothelioma transplant recipients Recurrent metabolic 100 encephalomyopathic crises- 24 Cases 75326 Retinal arterial tortuosity Cases 480864 rhabdomyolysis-cardiac

arrhythmia-intellectual disability Retinal degeneration- 7 Cases syndrome 1574 nanophthalmos-glaucoma 4 syndrome 97239 Reducing body myopathy Families Retinal dystrophy with inner 14 Cases 397758 retinal dysfunction and ganglion Refractory anemia with excess 0.15 I* 86839 cell anomalies blasts Retinal ischemic syndrome- Refractory anemia with excess 0.04 I* digestive tract small vessel 3 Cases 168960 3018 blasts in transformation hyalinosis-diffuse cerebral 0.1 P* calcifications syndrome 773 Refsum disease 5

60 Cases 319640 Retinal macular dystrophy type 2 Families 773 Refsum disease

140 30.0 P* 791 Retinitis pigmentosa 83450 Regional odontodysplasia Cases

26.7 P 791 Retinitis pigmentosa Regressive spondylometaphyseal 2 Cases 448267 dysplasia Retinitis pigmentosa-hearing 81 Cases loss-premature aging-short 3 Cases 98961 Reis-Bücklers corneal dystrophy 494439 stature-facial dysmorphism 0.35 I syndrome 728 Relapsing polychondritis Retinitis pigmentosa-intellectual 2

1.7 BP* 3085 disability-deafness- Families 1848 Renal agenesis, bilateral hypogonadism syndrome Retinitis pigmentosa-juvenile 50.0 BP 3 Cases 93100 Renal agenesis, unilateral 436245 cataract-short stature-

2838 Renal caliceal diverticuli- 4 Cases intellectual disability syndrome

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 76 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 0.125 P 16 Cases 52427 Retinitis punctata albescens 1438 Ring chromosome 10 syndrome

0.175 P* 20 Cases 52427 Retinitis punctata albescens 96175 Ring chromosome 11 syndrome

0.05 I* 10 Cases 790 Retinoblastoma 1439 Ring chromosome 12 syndrome

6.0 BP 80 Cases 790 Retinoblastoma 1440 Ring chromosome 14 syndrome

1.05 50 Cases 790 Retinoblastoma 96177 Ring chromosome 15 syndrome

5.0 BP* 10 Cases 778 Rett syndrome 96178 Ring chromosome 16 syndrome

10.0 P* 18 Cases 778 Rett syndrome 1441 Ring chromosome 17 syndrome

Reunion Island Larsen-like 30 Cases 70 Cases 294049 1442 Ring chromosome 18 syndrome syndrome 4 Cases 10 Cases 3088 Revesz syndrome 1443 Ring chromosome 19 syndrome

500 18 Cases 96171 Ring chromosome 2 syndrome 69077 Rhabdoid tumor Cases

50 Cases 1444 Ring chromosome 20 syndrome 0.59 I* 780 Rhabdomyosarcoma 100

5.0 I* 1446 Ring chromosome 22 syndrome Cases 3099 Rheumatic fever

Rheumatoid factor-negative 11 Cases 8.0 P* 96172 Ring chromosome 3 syndrome 85408 polyarticular juvenile idiopathic

arthritis 20 Cases 1447 Ring chromosome 4 syndrome Rheumatoid factor-positive 4.2 P* 85435 polyarticular juvenile idiopathic 25 Cases 1448 Ring chromosome 6 syndrome arthritis Rhizomelic chondrodysplasia 1.0 P* 18 Cases 177 1449 Ring chromosome 7 syndrome punctata Rhizomelic chondrodysplasia 4 Cases 8 Cases 468717 1450 Ring chromosome 8 syndrome punctata type 5 Rhizomelic dysplasia, Patterson- 5 Cases 31 Cases 2831 96173 Ring chromosome 9 syndrome Lowry type Rhizomelic syndrome, Urbach 3 Cases 30 Cases 3098 91481 Ring dermoid of cornea type 100 150

59315 Rhombencephalosynapsis Cases 3103 Roberts syndrome Cases

109 Robin sequence-oligodactyly 3 Cases 97229 Riboflavin transporter deficiency Cases 3104 syndrome 200

1 Case 97360 Robinow syndrome Cases 440706 Ribose-5-P isomerase deficiency

33 Cases 7 Cases 3102 Richieri Costa-Pereira syndrome 353298 Roifman syndrome

4 Cases Rolandic epilepsy-paroxysmal 3101 Richieri Costa-da Silva syndrome 1 Family 163727 exercise-induced dystonia-

800 writer's cramp syndrome

83312 Rickettsialpox Cases 40.0 P* 101016 Romano-Ward syndrome

2.0 BP 1000 363203 Ring chromosome 158014 Rosaï-Dorfman disease Cases

35 Cases 1437 Ring chromosome 1 syndrome

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 77 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

2909 Rothmund-Thomson syndrome Cases STING-associated vasculopathy 9 Cases 425120 with onset in infancy 100 Rothmund-Thomson syndrome 2 Cases 221008 Cases 370921 STT3A-CDG type 1 1 Case 200 370924 STT3B-CDG Rothmund-Thomson syndrome 221016 Cases 6.7 P* type 2 57145 SUNCT syndrome

50 Cases SURF1-related Charcot-Marie- 3 Cases 3111 Rotor syndrome 391351 Tooth disease type 4 20 Cases SYNGAP1-related developmental 57 Cases 83616 Rubella panencephalitis 544254 and epileptic encephalopathy 0.7 BP* 783 Rubinstein-Taybi syndrome Sacral agenesis-abnormal ossification of the vertebral 4 Cases Rubinstein-Taybi syndrome due 34 Cases 397927 353284 bodies-persistent notochordal to EP300 haploinsufficiency canal syndrome S-adenosylhomocysteine 4 Cases 3.0 BP* 88618 794 Saethre-Chotzen syndrome hydrolase deficiency SATB2-associated syndrome due 20 Cases 60 Cases 251028 to a chromosomal 300493 Sagliker syndrome

rearrangement 13 Cases 4 Cases 140969 Saldino-Mainzer syndrome 370052 SCALP syndrome Salivary gland type cancer of the 0.05 I* 2 Cases 213557 3134 SCARF syndrome breast 0.67 BP* 3 Cases 796 Sandhoff disease 139466 SERKAL syndrome 0.32 P* 32 Cases 79269 Sanfilippo syndrome type A 3163 SHORT syndrome 1.4 BP SIM1-related Prader-Willi-like 4 Cases 79269 Sanfilippo syndrome type A 398079 syndrome 0.2 P* SIX2-related frontonasal 1 Family 79270 Sanfilippo syndrome type B 488437 dysplasia 5.0 P* 3 Cases 79271 Sanfilippo syndrome type C 238459 SLC35A1-CDG 20.0 P* 4 Cases 797 Sarcoidosis 356961 SLC35A2-CDG 2.0 BP SLC39A13-related 3129 Sarcosinemia 8 Cases 157965 spondylodysplastic Ehlers-Danlos 50 Cases 3130 Satoyoshi syndrome syndrome 10 Cases 4 Cases 468699 SLC39A8-CDG 3132 Say-Barber-Miller syndrome

SMARCA4-deficient sarcoma of 19 Cases 4 Cases 466962 3133 Say-Field-Coldwell syndrome thorax 16 Cases Scalp defects-postaxial 2 Cases 93357 SPONASTRIME dysplasia 1003 polydactyly syndrome 7 30 Cases 324737 SRD5A3-CDG Families 2036 Scalp-ear-nipple syndrome

Scapuloperoneal spinal muscular 31 Cases 9 Cases 431255 370927 SSR4-CDG atrophy Scarring in glaucoma filtration 22.0 P* 90080 STAG1-related intellectual surgical procedures disability-facial dysmorphism- 17 Cases 18 Cases 502434 2353 Schilbach-Rott syndrome gastroesophageal reflux syndrome Schimke immuno-osseous 71 Cases STAT3-related early-onset 19 Cases 1830 438159 dysplasia multisystem autoimmune

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 78 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 46 Cases 798 Schinzel-Giedion syndrome 10.0 BP* 3157 Septo-optic dysplasia spectrum 150

37748 Schnitzler syndrome Cases 1.0 I 157798 Serrated polyposis syndrome

115 Severe X-linked intellectual 7 Cases 98967 Schnyder corneal dystrophy Cases 3078 disability, Gustavson type Severe X-linked mitochondrial 2 Cases 129 238329 encephalomyopathy 800 Schwartz-Jampel syndrome Cases Severe achondroplasia- 5 Cases 85165 developmental delay-acanthosis Schöpf-Schulz-Passarge 25 Cases 50944 nigricans syndrome syndrome Severe autosomal recessive 2 Cases 2.0 BP* 438207 185 Scimitar syndrome macrothrombocytopenia Severe combined 1.65 BP* 1.41 I 183660 801 Scleroderma immunodeficiency Severe combined 3 Cases 42.0 P 357237 immunodeficiency due to 801 Scleroderma CARD11 deficiency 250 Severe combined 21 Cases 167635 Scleromyxedema Cases 542301 immunodeficiency due to

CARMIL2 deficiency Scleromyxedema without 15 Cases Severe combined 90400 9 Cases monoclonal gammopathy 228003 immunodeficiency due to

80 Cases CORO1A deficiency 3152 Sclerosteosis Severe combined 12 Cases 4 Cases 420573 immunodeficiency due to CTPS1 806 Scott syndrome deficiency 60 Cases Severe combined 158029 Sea-blue histiocytosis 2 Cases 317425 immunodeficiency due to DNA-

Seborrhea-like dermatitis with 44 Cases PKcs deficiency 168606 psoriasiform elements Severe combined 9 Cases 50 Cases 169095 immunodeficiency due to FOXN1 808 Seckel syndrome deficiency Severe combined 0.2 BP* 9 Cases 808 Seckel syndrome 397787 immunodeficiency due to IKK2

Segmental odontomaxillary 32 Cases deficiency 67039 Severe combined dysplasia 3 Cases Segmental progressive 504523 immunodeficiency due to LAT 10 Cases 314662 overgrowth syndrome with deficiency Severe combined fibroadipose hyperplasia 4 Cases Seizures-intellectual disability 280142 immunodeficiency due to LCK 6 Cases 79156 due to hydroxylysinuria deficiency Severe combined syndrome 0.3 BP* Seizures-scoliosis-macrocephaly 10 Cases 277 immunodeficiency due to 466926 syndrome adenosine deaminase deficiency Severe combined 25 Cases 0.2 P* 281122 Self-improving collodion baby 277 immunodeficiency due to

150 adenosine deaminase deficiency Severe combined 3156 Senior-Loken syndrome Cases 1.0 P* 331206 immunodeficiency due to

2 complete RAG1/2 deficiency Sensorineural deafness with 217622 Families Severe congenital hypochromic 3 Cases dilated cardiomyopathy 300298 anemia with ringed sideroblasts Sensorineural hearing loss-early 0.4 BP* 3 Cases 42738 Severe congenital neutropenia 66633 graying-essential tremor 0.07 P syndrome 42738 Severe congenital neutropenia 90051 Sepsis in premature infants 32.0 P*

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 79 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 0.4 P* disabilities-sensorineural 42738 Severe congenital neutropenia deafness-dystonia syndrome Severe dermatitis-multiple Severe myopia-generalized joint 5 Cases 3 Cases 527450 369992 allergies-metabolic wasting laxity-short stature syndrome

syndrome Severe neonatal hypotonia- Severe early-onset obesity- seizures-encephalopathy 7 Cases 13 Cases 314655 329249 insulin resistance syndrome due syndrome due to 5q31.3

to SH2B1 deficiency microdeletion Severe feeding difficulties-failure Severe neonatal lactic acidosis 28 Cases 5 Cases 352577 to thrive-microcephaly due to 397593 due to NFS1-ISD11 complex

ASXL3 deficiency syndrome deficiency Severe growth deficiency- Severe neonatal-onset 30 Cases strabismus-extensive dermal 3 Cases 209370 encephalopathy with 488627 melanocytosis-intellectual microcephaly disability syndrome Severe neurodegenerative 10 Cases 363400 2.8 P* syndrome with lipodystrophy 169802 Severe hemophilia A Severe neurodevelopmental 0.8 P* disorder with feeding difficulties- 6 Cases 169793 Severe hemophilia B 500545 stereotypic hand movement- Severe hereditary thrombophilia bilateral cataract 0.16 BP 745 due to congenital protein C Severe oculo-renal-cerebellar 5 Cases 2715 deficiency syndrome Severe hypotonia-psychomotor 0.02 I* 6 Cases 363489 Sex cord-stromal tumor of testis 467176 developmental delay-strabismus-

cardiac septal defect syndrome 0.44 363489 Sex cord-stromal tumor of testis Severe intellectual disability and 15 Cases 280763 progressive spastic paraplegia 1.68 I* 810 Shigellosis Severe intellectual disability- corpus callosum agenesis-facial 6 Cases 100 466688 dysmorphism-cerebellar ataxia 99063 Shone complex Cases

syndrome Severe intellectual disability- 2 Cases 2.0 P* 94066 epilepsy-anal anomalies-distal 104008 Short bowel syndrome

phalangeal hypoplasia Short fifth metacarpals-insulin 6 Cases Severe intellectual disability- 66518 6 Cases resistance syndrome 436141 hypotonia-strabismus-coarse Short rib-polydactyly syndrome 2 Cases 498497 face-planovalgus syndrome type 5 Severe intellectual disability- Short rib-polydactyly syndrome, 34 Cases poor language-strabismus- 4 Cases 93269 363686 Majewski type grimacing face-long fingers Short stature due to GHSR 8 Cases 314811 syndrome deficiency Severe intellectual disability- Short stature due to growth 3 Cases progressive postnatal 3 Cases 629 397933 hormone qualitative anomaly microcephaly-midline stereotypic 2 Cases hand movements syndrome 2867 Short stature, Brussels type

Severe intellectual disability- 4 Cases Short stature-advanced bone 3 404473 progressive spastic diplegia 435804 age-early-onset osteoarthritis Families syndrome syndrome Severe intellectual disability- Short stature-auditory canal short stature-behavioral 3 Cases 4 Cases 391307 397623 atresia-mandibular hypoplasia- abnormalities-facial skeletal anomalies syndrome dysmorphism syndrome Short stature-brachydactyly- Severe lateral tibial bowing with 2 Cases 6 Cases 324307 464288 obesity-global developmental short stature delay syndrome Severe microbrachycephaly- 2 Cases Short stature-craniofacial 3 1236 intellectual disability-athetoid 2994 anomalies-genital hypoplasia Families cerebral palsy syndrome syndrome 369939 Severe motor and intellectual 7 Cases 2866 Short stature-deafness- 2 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 80 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families neutrophil dysfunction- 0.71 BP* 3169 Sirenomelia dysmorphism syndrome Short stature-onychodysplasia- 0.01 P 14 Cases 3169 Sirenomelia 314394 facial dysmorphism-

hypotrichosis syndrome 0.009 P* 3169 Sirenomelia Short stature-optic atrophy- 39 Cases 391677 Pelger-Huët anomaly syndrome 100

Short stature-pituitary and 5 2882 Sitosterolemia Cases

85442 cerebellar defects-small sella Families

turcica syndrome 0.13 I* 319 Skeletal Ewing sarcoma Short stature-valvular heart 3 Cases 2868 disease-characteristic facies 2.33 319 Skeletal Ewing sarcoma syndrome Short stature-webbed neck-heart 4 Cases Skeletal dysplasia-T-cell 2865 12 Cases disease syndrome 508533 immunodeficiency-

Short stature-wormian bones- 3 Cases developmental delay syndrome 2863 dextrocardia syndrome Skeletal dysplasia-epilepsy-short 7 Cases 1858 Short tarsus-absence of lower 11 Cases stature syndrome 2832 eyelashes syndrome Skeletal overgrowth-craniofacial 2 Cases Short ulna-dysmorphism- 477831 dysmorphism-hyperelastic skin- 4 Cases 357175 hypotonia-intellectual disability white matter lesions syndrome

syndrome Skin fragility-woolly hair- 7 Cases Short-limb skeletal dysplasia 293165 palmoplantar keratoderma 19 Cases 935 with severe combined syndrome

immunodeficiency 12.0 P* 70573 Small cell lung cancer 60 Cases 2462 Shprintzen-Goldberg syndrome 11

0.5 BP 93974 Smith-Fineman-Myers syndrome Families 811 Shwachman-Diamond syndrome

0.28 P 3.7 BP* 811 Shwachman-Diamond syndrome 818 Smith-Lemli-Opitz syndrome

0.05 BP* 4.0 P 309294 Sialidosis 819 Smith-Magenis syndrome

5 Cases 5.35 P* 3166 Sialuria 819 Smith-Magenis syndrome

10.0 P* 16 Cases 232 Sickle cell anemia 178355 Smith-McCort dysplasia

2 Cases 0.4 I* 3167 Siegler-Brewer-Carey syndrome 820 Sneddon syndrome

98 Cases Snowflake vitreoretinal 50 Cases 71276 Silent sinus syndrome 91496 degeneration 5 Cases Sodium channelopathy-related 8 Cases 3168 Sillence syndrome 306577 small fiber neuropathy 15.5 I* 30.0 P* 813 Silver-Russell syndrome 3394 Soft tissue sarcoma

0.7 BP* 4.74 I* 813 Silver-Russell syndrome 3394 Soft tissue sarcoma

Silver-Russell syndrome due to a 8 Cases Solid pseudopapillary carcinoma 0.003 I* 397590 424065 point mutation of pancreas 250 1.0 I* Simpson-Golabi-Behmel 209964 Solitary rectal ulcer syndrome 373 Cases syndrome 0.0025 I* 97283 Somatostatinoma 22 Cases 85191 Singleton-Merten dysplasia 7.1 BP 821 Sotos syndrome Sinoatrial node dysfunction and 8 Cases 324321 deafness 0.5 BP* 821 Sotos syndrome 0.98 BP 3169 Sirenomelia

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 81 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 3 respiratory distress type 2 Spastic ataxia with congenital 1182 Families Spinal muscular atrophy-Dandy- miosis 2 Cases 73245 Walker malformation-cataracts

Spastic ataxia-corneal dystrophy 1 Family syndrome 2572 syndrome Spinal muscular atrophy- 10 Cases Spastic ataxia-dysarthria due to 5 Cases 2590 progressive myoclonic epilepsy 557056 glutaminase deficiency syndrome Spastic paraparesis-deafness 6 Cases 1.5 P 2815 98755 Spinocerebellar ataxia type 1 syndrome 100 51 Cases 98767 Spinocerebellar ataxia type 11 99015 Spastic paraplegia type 2 Cases

4.0 P* 98762 Spinocerebellar ataxia type 12 Families 99013 Spastic paraplegia type 7

Spastic paraplegia-Paget disease 1 Family 20 Cases 329475 98768 Spinocerebellar ataxia type 13 of bone syndrome Spastic paraplegia-facial- 5 Cases 20 2819 cutaneous lesions syndrome 98763 Spinocerebellar ataxia type 14 Families

2 Spastic paraplegia-glaucoma- 2818 Families Spinocerebellar ataxia type 80 Cases intellectual disability syndrome 98769 15/16 Spastic paraplegia-intellectual 100 4 Cases 521390 disability-nystagmus-obesity 98759 Spinocerebellar ataxia type 17 Families

syndrome Spastic paraplegia-nephritis- 4 Cases 26 Cases 2820 98771 Spinocerebellar ataxia type 18 deafness syndrome Spastic paraplegia-neuropathy- 1 Family Spinocerebellar ataxia type 12 Cases 2821 98772 poikiloderma syndrome 19/22 Spastic paraplegia-optic atrophy- 75 Cases 1.5 P 320406 98756 Spinocerebellar ataxia type 2 neuropathy syndrome Spastic paraplegia-precocious 2 Cases 20 Cases 2826 101110 Spinocerebellar ataxia type 20 puberty syndrome Spastic paraplegia-severe 35 Cases 16 Cases 98773 Spinocerebellar ataxia type 21 464282 developmental delay-epilepsy

syndrome 4

Spastic tetraplegia-retinitis 101108 Spinocerebellar ataxia type 23 Families 2 Cases 3011 pigmentosa-intellectual disability

syndrome 10 Cases 101111 Spinocerebellar ataxia type 25 Spastic tetraplegia-thin corpus 15 Cases 447997 callosum-progressive postnatal 1 Family 101112 Spinocerebellar ataxia type 26 microcephaly syndrome 2 Spectrin-associated autosomal 30 Cases 352403 Families 98764 Spinocerebellar ataxia type 27 recessive cerebellar ataxia 50 Cases 0.03 I* 208513 Spinocerebellar ataxia type 29 99865 Spermatocytic seminoma 1.5 P Spigelian hernia-cryptorchidism 15 Cases 98757 Spinocerebellar ataxia type 3 314432 syndrome 6 Cases Spinal arteriovenous metameric 45 Cases 211017 Spinocerebellar ataxia type 30 53721 syndrome 30

Spinal atrophy-ophthalmoplegia- 2 Cases 217012 Spinocerebellar ataxia type 31 Families 1217 pyramidal syndrome 32.0 P* 1 Family 90058 Spinal cord injury 276183 Spinocerebellar ataxia type 32

128 Spinal muscular atrophy with 45 Cases 98920 Cases 1955 Spinocerebellar ataxia type 34 respiratory distress type 1 28 Cases 276193 Spinocerebellar ataxia type 35 404521 Spinal muscular atrophy with 1 Case

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 82 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 100 234 Spondyloepimetaphyseal 276198 Spinocerebellar ataxia type 36 Families 99642 Cases dysplasia, Handigodu type

9 Cases Spondyloepimetaphyseal 2 Cases 363710 Spinocerebellar ataxia type 37 370015 dysplasia, Isidor type 4 Spondyloepimetaphyseal 14 Cases 93356 423296 Spinocerebellar ataxia type 38 Families dysplasia, Missouri type

Spondyloepimetaphyseal 17 Cases 93282 5 Cases dysplasia, PAPSS2 type 423275 Spinocerebellar ataxia type 40 Spondyloepimetaphyseal 5 Cases 93352 1 Case dysplasia, Shohat type 458798 Spinocerebellar ataxia type 41 Spondyloepimetaphyseal 3 Cases 171866 25 Cases dysplasia, aggrecan type 458803 Spinocerebellar ataxia type 42 Spondyloepimetaphyseal 5 Cases 156728 7 Cases dysplasia, matrilin-3 type 497764 Spinocerebellar ataxia type 43 Spondyloepimetaphyseal 2 Cases 5 168451 dysplasia-abnormal dentition

98766 Spinocerebellar ataxia type 5 Families syndrome

Spondyloepimetaphyseal 5 Cases Spinocerebellar ataxia with 9 Cases 168443 dysplasia-hypotrichosis 94124 axonal neuropathy type 1 syndrome Spinocerebellar ataxia- 3 Cases Spondyloepimetaphyseal 1185 27 Cases dysmorphism syndrome 93358 dysplasia-short limb-abnormal

Spinocerebellar degeneration- 2 Cases calcification syndrome 3177 corneal dystrophy syndrome Spondyloepiphyseal dysplasia 1.0 BP* 94068 0.5 P* congenita 86854 Splenic marginal zone lymphoma Spondyloepiphyseal dysplasia 3 Cases 163665 Splenogonadal fusion-limb 30 Cases tarda, Kohn type 2063 defects-micrognathia syndrome 13 Spondyloepiphyseal dysplasia Split hand-split foot-deafness 22 Cases 137678 Families 71271 with metatarsal shortening syndrome Split-foot malformation- 5 Cases Spondyloepiphyseal dysplasia, 4 Cases 488232 163654 mesoaxial polydactyly syndrome Cantu type Spondylo-megaepiphyseal- 19 Cases Spondyloepiphyseal dysplasia, 1 Family 228387 93283 metaphyseal dysplasia Kimberley type 7 Cases Spondyloepiphyseal dysplasia, 4 Cases 85194 Spondylo-ocular syndrome 163668 MacDermot type Spondylocamptodactyly 5 Cases Spondyloepiphyseal dysplasia, 10 Cases 3180 263482 syndrome Maroteaux type 35 Cases Spondyloepiphyseal dysplasia, 4 Cases 3275 Spondylocarpotarsal synostosis 163649 Nishimura type Spondylocostal dysostosis-anal Spondyloepiphyseal dysplasia, 1 Family 3 Cases 163662 94095 atresia-genitourinary Reardon type

malformation syndrome Spondyloepiphyseal dysplasia, 7 Cases 459051 Spondylocostal dysostosis- Stanescu type 2 Cases 329252 hypospadias-intellectual 1.0 BP* 254 Spondylometaphyseal dysplasia disability syndrome 24 Spondylometaphyseal dysplasia, 30 Cases Spondylodysplastic Ehlers-Danlos 93315 536471 Families 'corner fracture' type syndrome Spondylometaphyseal dysplasia, 3 Cases 168555 36 Cases A4 type 1855 Spondyloenchondrodysplasia Spondylometaphyseal dysplasia, 2 Cases 370019 Spondyloepimetaphyseal Czarny-Ratajczak type 30 Cases 93346 dysplasia congenita, Strudwick Spondylometaphyseal dysplasia, 3 Cases 168544 type Golden type 6 Spondyloepimetaphyseal Spondylometaphyseal dysplasia, 7 Cases 168454 Families 93316 dysplasia, Geneviève type Schmidt type

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 83 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Spondylometaphyseal dysplasia, 9 Cases small intestine 93317 Sedaghatian type Squamous cell carcinoma of the 0.115 I* 418959 Spondylometaphyseal dysplasia- stomach 2 Cases 168552 bowed forearms-facial 0.38 I* 83484 St. Louis encephalitis dysmorphism syndrome Spondylometaphyseal dysplasia- 18 Cases 6 85167 Stapes ankylosis with broad cone-rod dystrophy syndrome 140917 Families thumbs and toes 10 Spondyloperipheral dysplasia- 1856 Families 13.0 P* short ulna syndrome 827 Stargardt disease

Spontaneous periodic 50 Cases 40 Cases 29822 438117 Steel syndrome hypothermia Sporadic Creutzfeldt-Jakob 0.1 P* 5.0 P* 204 273 Steinert myotonic dystrophy disease Sporadic Creutzfeldt-Jakob 0.15 I 12.5 P 204 273 Steinert myotonic dystrophy disease Sporadic adult-onset ataxia of 7.6 P* Sterile multifocal osteomyelitis 17 Cases 247234 210115 unknown etiology with periostitis and pustulosis Squamous cell carcinoma of 0.032 I* 2.0 BP* 424996 gallbladder and extrahepatic 2017 Sternal cleft

biliary tract Steroid dehydrogenase 1 Family Squamous cell carcinoma of liver 0.009 I* 3196 deficiency-dental anomalies 424975 and intrahepatic biliary tract syndrome Squamous cell carcinoma of 0.023 I* 0.36 I* 424039 36426 Stevens-Johnson syndrome pancreas Squamous cell carcinoma of the 0.81 I* Stevens-Johnson syndrome/toxic 0.19 I 424019 95455 anal canal epidermal necrolysis spectrum Squamous cell carcinoma of the 4.28 I* 1.0 BP* 213767 828 Stickler syndrome cervix uteri Squamous cell carcinoma of the 0.026 I* 12.2 BP 423994 828 Stickler syndrome colon Squamous cell carcinoma of the 0.12 I* 54 Cases 213716 2833 Stiff skin syndrome corpus uteri Squamous cell carcinoma of the 3.357 I* 2 Cases 99977 3199 Stimmler syndrome esophagus Squamous cell carcinoma of the 5.2 I Stormorken-Sjaastad-Langslet 17 Cases 99977 3204 esophagus syndrome Squamous cell carcinoma of the 5.42 11 Cases 99977 506307 Stromme syndrome esophagus Squamous cell carcinoma of the 1.27 I* 3.5 BP* 494547 3205 Sturge-Weber syndrome hypopharynx Squamous cell carcinoma of the 4.61 I* 56 Cases 494550 3206 Stüve-Wiedemann syndrome larynx Squamous cell carcinoma of the 1.02 I Subaortic stenosis-short stature 1 Family 502366 3191 lip syndrome Squamous cell carcinoma of the 200 0.35 I 500464 nasal cavity and paranasal 48377 Subcorneal pustular dermatosis Cases

sinuses Squamous cell carcinoma of the 3.51 I* Subepithelial mucinous corneal 1 Family 502363 98959 oral cavity dystrophy Squamous cell carcinoma of the 3.12 I* 450 500478 Succinic semialdehyde oropharynx 22 Cases dehydrogenase deficiency Squamous cell carcinoma of the 0.57 I* 398058 penis Succinyl-CoA:3-oxoacid CoA 32 Cases 832 Squamous cell carcinoma of the 0.113 I* transferase deficiency 424002 rectum Sudden infant death-dysgenesis 21 Cases 168593 423968 Squamous cell carcinoma of the 0.008 I* of the testes syndrome

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 84 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families 1 Family Syndromic multisystem 498602 Sugarman brachydactyly 10 Cases 228426 autoimmune disease due to Itch

3 Cases deficiency 3210 Summitt syndrome 2 Syndromic orbital border Superficial epidermolytic 20 Cases 98606 Families 455 hypoplasia ichthyosis 1.2 P* Syndromic recessive X-linked 1.3 P* 46485 Superficial pemphigus 281090 ichthyosis 300 Syndromic sensorineural 2 Cases 247245 Superficial siderosis Cases 457223 deafness due to combined

oxidative phosphorylation defect 300 32 Cases Syringocystadenoma 141096 Supernumerary nostril 840 Cases papilliferum 5 Cases 466695 Supratip dysplasia 8.4 P* 3280 Syringomyelia 4.0 BP* 3193 Supravalvular aortic stenosis 150

13.3 P* 188 Systemic capillary leak syndrome Cases 3193 Supravalvular aortic stenosis

304 0.6 I* 2467 Systemic mastocytosis 838 Susac syndrome Cases 11.3 P* 2467 Systemic mastocytosis Susceptibility to infection due to 8 Cases 331226 Systemic primary carnitine 3.2 BP* TYK2 deficiency 158 Symbrachydactyly of hands and 2 Cases deficiency 1570 15.4 P* feet 90291 Systemic sclerosis Symmetrical thalamic 30 Cases 1314 Systemic-onset juvenile 5.0 P* calcifications 85414 0.6 P* idiopathic arthritis 79098 Sympathetic ophthalmia T-B+ severe combined 3 Cases Symphalangism with multiple 6 Cases 169157 immunodeficiency due to CD45 3246 anomalies of hands and feet deficiency 25.0 BP* T-cell immunodeficiency with 2 Cases 93402 Syndactyly type 1 324294 epidermodysplasia verruciformis 4 Cases T-cell large granular lymphocyte 0.4 I* 93405 Syndactyly type 4 86872 leukemia 10 Cases 0.99 I* 93406 Syndactyly type 5 171918 T-cell non-Hodgkin lymphoma

Syndactyly-camptodactyly and 28 Cases 26 Cases 457077 TAFRO syndrome 357332 clinodactyly of fifth fingers-bifid 6 toes syndrome Syndactyly-nystagmus syndrome 2 Cases 2886 TARP syndrome Families 294026 due to 2q31.1 microduplication Syndactyly-polydactyly-ear lobe 10 Cases TBCK-related intellectual 25 Cases 3259 488632 syndrome disability syndrome Syndactyly-telecanthus- TCR-alpha-beta-positive T-cell 2 Cases 6 Cases 397959 140952 anogenital and renal deficiency TELO2-related intellectual malformations syndrome 6 Cases Syndromic X-linked intellectual 10 Cases 488642 disability-neurodevelopmental 85274 disability 7 disorder Syndromic X-linked intellectual 10 10 Cases 284227 TEMPI syndrome 85279 disability due to JARID1C Families THOC6-related developmental mutation 4 Cases 116 363444 delay-microcephaly-facial

84064 Syndromic diarrhea Cases dysmorphism syndrome 6 Cases 314667 TMEM165-CDG Syndromic microphthalmia type 20 Cases 178364 5 466703 TMEM199-CDG 7 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 85 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families Families TMEM94-associated congenital 10 Cases 562569 heart defect-facial dysmorphism- 2 Cases 141258 Tessier number 4 facial cleft developmental delay syndrome TNP03-related limb-girdle 64 Cases Testicular seminomatous germ 1.71 I* 55595 842 muscular dystrophy D2 cell tumor TOR1AIP1-related limb-girdle 3 Cases Testicular seminomatous germ 46.01 424261 842 muscular dystrophy cell tumor TRAPPC11-related limb-girdle 3 Cases 0.04 369840 363483 Testicular teratoma muscular dystrophy R18 0.084 I* 0.024 I* 3287 Takayasu arteritis 3299 Tetanus

1.34 P* 5 3287 Takayasu arteritis Tetraamelia-multiple 3301 Families malformations syndrome Tall stature-intellectual 17 Cases 404443 disability-facial dysmorphism 34.0 BP 3303 Tetralogy of Fallot syndrome Tall stature-intellectual 29.3 BP* 4 Cases 3303 Tetralogy of Fallot 500095 disability-renal anomalies

syndrome 4.0 BP* 884 Tetrasomy 12p Tall stature-scoliosis- 2

329191 macrodactyly of the great toes Families 13 Cases 96055 Tetrasomy 21 syndrome 2 Cases 70 Cases 50809 Talo-patello-scaphoid osteolysis 3310 Tetrasomy 9p

100 50 Cases 31150 Tangier disease Cases 9 Tetrasomy X

2 Cases 10 1780 Thakker-Donnai syndrome

1412 Tarsal-carpal coalition syndrome Families 0.77 P 3312 Thalidomide embryopathy

0.31 BP* 3.5 BP* 845 Tay-Sachs disease 2655 Thanatophoric dysplasia

0.28 BP Thiamine-responsive 2 Cases 845 Tay-Sachs disease 199348 encephalopathy 5 Cases Thiamine-responsive 80 Cases 3291 Teebi-Shaltout syndrome 49827 megaloblastic anemia syndrome Telecanthus-hypertelorism- 2 Cases 2 3293 Thickened earlobes-conductive strabismus-pes cavus syndrome 2405 Families Telethonin-related limb-girdle 16 Cases deafness syndrome 34514 muscular dystrophy R7 173

Temperature-sensitive 10 Cases 98960 Thiel-Behnke corneal dystrophy Cases 352737 oculocutaneous albinism type 1 53 Cases Thin ribs-tubular bones- 2 Cases 254516 Temple syndrome 1506 dysmorphism syndrome Temple syndrome due to 64 Cases 6 Cases 96184 maternal uniparental disomy of 3316 Thomas syndrome

chromosome 14 1.0 P Temple syndrome due to 614 Thomsen and Becker disease 12 Cases 254531 paternal 14q32.2 Thoracic dysplasia- 2 Cases 1861 hypomethylation hydrocephalus syndrome Temple syndrome due to 9 Cases 10 Cases 254525 3317 Thoracolaryngopelvic dysplasia paternal 14q32.2 microdeletion 8 Cases 2 Cases 420561 Temple-Baraitser syndrome 1803 Thoracomelic dysplasia

Temtamy preaxial brachydactyly 18 Cases Thrombocythemia with distal 3 363417 329319 syndrome limb defects Families 1777 Temtamy syndrome 7

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 86 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Thrombocytopenia with 3 Toriello-Lacassie-Droste 19 Cases 3339 67044 congenital dyserythropoietic Families syndrome

anemia Torticollis-keloids- 7 Cases Thrombocytopenia-absent radius 0.5 BP* 3341 cryptorchidism-renal dysplasia 3320 syndrome syndrome Thrombomodulin-related 15 Cases 20000 436169 bleeding disorder 227972 Toxic oil syndrome Cases

Thrombotic thrombocytopenic 25.5 P* 54057 purpura 2.0 BP* 3346 Tracheal agenesis 2 Thumb deformity-alopecia- 2251 Families 400 pigmentation anomaly syndrome Tracheobronchopathia 3348 Cases osteochondroplastica Thumb stiffness-brachydactyly- 7 Cases 1078 intellectual disability syndrome 23 Cases 101028 Transaldolase deficiency 0.17 I* 3398 Thymic epithelial neoplasm 40 Cases 859 Transcobalamin deficiency 3 Cases 3326 Thymic-renal-anal-lung dysplasia Transient antenatal Bartter 15 Cases 570371 0.14 I* syndrome 99867 Thymoma Transient bullous dermolysis of 30 Cases 79411 1.22 the newborn 99867 Thymoma Transient infantile 11 Cases 2 Cases 300293 hypertriglyceridemia and 3327 Thyrocerebrorenal syndrome hepatosteatosis 3.65 I* Transient neonatal diabetes 0.3 BP* 100088 Thyroid carcinoma 99886 mellitus 3.1 I Transient neonatal multiple acyl- 1 Case 100088 Thyroid carcinoma 329942 CoA dehydrogenase deficiency 61.7 5 Cases 100088 Thyroid carcinoma 488618 Transketolase deficiency

12.7 P Transposition of the great 31.7 BP* 100088 Thyroid carcinoma 216675 arteries 14.3 P* 2.0 BP* 95712 Thyroid ectopia 861 Treacher-Collins syndrome

25.0 P Tremor-ataxia-central 7 Cases 95719 Thyroid hemiagenesis 447896 hypomyelination syndrome 3.5 P Tremor-nystagmus-duodenal 17 Cases 95720 Thyroid hypoplasia 3350 ulcer syndrome 3.2 I 0.06 I* 100087 Thyroid tumor 863 Trichinellosis

5.0 I* 30 Cases 100087 Thyroid tumor 3352 Tricho-dento-osseous syndrome

Tibial aplasia-ectrodactyly 0.1 P* Tricho-retino-dento-digital 9 Cases 3329 1264 syndrome syndrome 5 0.1 BP* 93322 Tibial hemimelia 3351 Trichodental syndrome Families

6.0 P* 609 Tibial muscular dystrophy Trichodermodysplasia-dental 3 Cases 3353 2 alterations syndrome

42665 Tietz syndrome Families Trichodysplasia-amelogenesis 1 Family 79129 imperfecta syndrome 20 Cases Trichodysplasia-xeroderma 1 Family 65283 Timothy syndrome 3361 syndrome Trichomegaly-retina pigmentary Titin-related limb-girdle 1 Family 14 Cases 140922 3363 degeneration-dwarfism muscular dystrophy R10 3338 Toriello-Carey syndrome 59 Cases syndrome

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 87 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

100 236 Trisomy 9p Cases Trichorhinophalangeal syndrome 77258 Cases type 1 and 3 42.5 P* 3375 Trisomy X 100 Trichorhinophalangeal syndrome 502 Cases 4.8 P* type 2 88629 Tritanopia

201 4.3 BP 33364 Trichothiodystrophy Cases 3384 Truncus arteriosus

4.8 BP* 0.12 BP* 3384 Truncus arteriosus 33364 Trichothiodystrophy 139.0 I 4.2 BP* 3389 Tuberculosis 1209 Tricuspid atresia 9.0 I* 200 3389 Tuberculosis Triglyceride deposit 565612 Cases 16.0 P* cardiomyovasculopathy 3389 Tuberculosis

Trigonocephaly-bifid nose-acral 2 Cases 10.0 BP* 3368 805 Tuberous sclerosis complex anomalies syndrome Trigonocephaly-broad thumbs 2 Cases 10.0 P* 3365 805 Tuberous sclerosis complex syndrome Trigonocephaly-short stature- 3 Cases Tubular renal disease- 2 Cases 3369 73224 developmental delay syndrome cardiomyopathy syndrome Triose phosphate-isomerase 50 Cases Tubulinopathy-associated 7 Cases 868 467166 deficiency dysgyria 15 200 Triphalangeal thumb- 2950 Families 1063 Tufted angioma Cases polysyndactyly syndrome

4 Triphalangeal thumbs- 0.2 I* 2947 Families 3392 Tularemia brachyectrodactyly syndrome 2.0 P* 100 3392 Tularemia

869 Triple A syndrome Cases Tumor necrosis factor receptor 1 0.1 P* 32960 associated periodic syndrome 12.6 BP* 3.75 I* 3376 Triploidy 182130 Tumor of endocrine glands

50 Cases 64.0 P* 171929 Trisomy 10p 182130 Tumor of endocrine glands

40 Cases 3.15 I* 1699 Trisomy 12p 363472 Tumor of testis and paratestis

2.0 BP 87.77 1699 Trisomy 12p 363472 Tumor of testis and paratestis

3.7 BP* 5.5 BP* 3378 Trisomy 13 881 Turner syndrome

16.7 BP 3.0 I* 3380 Trisomy 18 99745 Typhoid

10.4 BP* 0.9 BP 3380 Trisomy 18 882 Tyrosinemia type 1

25 Cases 150 1715 Trisomy 18p 28378 Tyrosinemia type 2 Cases 18 Cases 261344 Trisomy 1q 20 Cases 85 Cases 69723 Tyrosinemia type 3 1738 Trisomy 4p 5 Cases 40 Cases 481665 USP18 deficiency 1742 Trisomy 5p 178338 UV-sensitive syndrome 7 Cases 1752 Trisomy 8q 30 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 88 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

84 Cases 38.0 P* 3403 Uhl anomaly 98715 Uveitis

1.0 BP 10 3403 Uhl anomaly 3412 VACTERL with hydrocephalus Families

3 Cases 3404 Ulbright-Hodes syndrome 6.25 BP* 887 VACTERL/VATER association Ulna hypoplasia-intellectual 2 Cases 2249 disability syndrome VPS11-related autosomal 13 Cases Ulna metaphyseal dysplasia 3 Cases 466934 recessive hypomyelinating 1837 syndrome leukodystrophy Vacuolar myopathy with Ulnar hypoplasia-split foot 1 Family 4 Cases 1122 88635 sarcoplasmic reticulum protein syndrome 117 aggregates

3138 Ulnar-mammary syndrome Cases 1 Family 3417 Van den Bosch syndrome

Ulnar/fibula ray defect- 1 Family 29 Cases 52056 2460 Van den Ende-Gupta syndrome brachydactyly syndrome Umbilical cord ulceration- 66 Cases 5 Cases 3405 314652 Variant ABeta2M amyloidosis intestinal atresia syndrome Unclassified acute myeloid 0.49 I* 6.3 P* 167714 52759 Vasculitis leukemia Undifferentiated carcinoma of 0.044 I* 48 Cases 418951 404553 Vasculitis due to ADA2 deficiency esophagus Undifferentiated carcinoma of 0.015 I* 2 Cases 424970 3424 Velo-facial-skeletal syndrome liver and intrahepatic biliary tract Undifferentiated carcinoma of 0.211 I* Ventriculomegaly-cystic kidney 11 Cases 423786 443988 stomach disease Undifferentiated pleomorphic 0.9 I* Verloove Vanhorick-Brubakk 2 Cases 2023 3429 sarcoma syndrome Unilateral multicystic dysplastic 23.2 BP 32.0 P* 97363 70476 Vernal keratoconjunctivitis kidney Unilateral multicystic dysplastic 14.8 BP* 37 Cases 97363 493342 Vibratory urticaria kidney 7.5 BP 50 Cases 1464 Univentricular heart 1493 Vici syndrome

Univentricular heart with single 2 Cases Virus-associated trichodysplasia 7 Cases 99069 228379 atrio-ventricular valve spinulosa Visceral neuropathy-brain 1 Family 2 Cases 3408 Upington disease 73246 anomalies-facial dysmorphism-

Upper limb defect-eye and ear 2 Cases developmental delay syndrome 2489 192 abnormalities syndrome Vitamin B12-responsive 4 Cases 28 Cases 2497 Upper limb mesomelic dysplasia methylmalonic acidemia

Vitamin B12-responsive 3 Cases 60 Cases 3409 Urban-Rogers-Meyer syndrome 79310 methylmalonic acidemia type

35.0 P* cblA 94059 Uremic pruritus Vitamin B12-unresponsive 450

4 Cases 79312 methylmalonic acidemia type Cases 210128 Urocanic aciduria mut- Uveal coloboma-cleft lip and 12 Cases 10 Cases 1473 3439 Von Voss-Cherstvoy syndrome palate-intellectual disability 0.5 I* 12.5 P 39044 Uveal melanoma 903 Von Willebrand disease

6.0 20.0 P* 39044 Uveal melanoma 137583 Vulvar intraepithelial neoplasia

380 98715 Uveitis 17.0 I* 83453 Vulvovaginal gingival syndrome Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 89 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families malformations 6 Cases White matter hypoplasia-corpus 2804 W syndrome 4 Cases 3207 callosum agenesis-intellectual

WAC-related facial disability syndrome dysmorphism-developmental 22 Cases 1 Family 466943 370131 White platelet syndrome delay-behavioral abnormalities syndrome 8.9 I* 1489 Whooping cough 0.2 BP 893 WAGR syndrome Wiedemann-Rautenstrauch 54 Cases 3455 WARS2-related combined 11 Cases syndrome 572798 oxidative phosphorylation defect 18 Cases 319182 Wiedemann-Steiner syndrome 65 Cases 51636 WHIM syndrome 4.5 P* 85446 Wild type ABeta2M amyloidosis 3

3466 WT limb-blood syndrome Families 30.0 P* 330001 Wild type ATTR amyloidosis

0.37 BP* 10.8 BP 3440 Waardenburg syndrome 904 Williams syndrome

100 1.8 BP* 897 Waardenburg-Shah syndrome Cases 904 Williams syndrome

2.2 BP 100 905 Wilson disease

898 Wagner disease Cases 3.3 P 905 Wilson disease

Waldenström 0.81 I* 6.0 P* 33226 905 Wilson disease macroglobulinemia 1.65 BP* 28 Cases 899 Walker-Warburg syndrome 3459 Wilson-Turner syndrome

4 Cases 0.1 P* 280558 Warsaw breakage syndrome 906 Wiskott-Aldrich syndrome

Warts-immunodeficiency- 2 Cases 15 Cases 568056 lymphedema-anogenital 500163 Witteveen-Kolk syndrome

dysplasia syndrome 60 Cases 48 Cases 1667 Wolcott-Rallison syndrome 3447 Weaver syndrome 2.0 BP* 2 Cases 280 Wolf-Hirschhorn syndrome 3448 Weaver-Williams syndrome 0.13 P 1.0 P 3463 Wolfram syndrome 3449 Weill-Marchesani syndrome 0.62 P* 100 3463 Wolfram syndrome

3344 Weismann-Netter syndrome Cases 25

3464 Woodhouse-Sakati syndrome Families 0.51 I* 99971 Well-differentiated liposarcoma Woolly hair-palmoplantar 8 Cases 200 420686 keratoderma syndrome 901 Wells syndrome Cases Wormian bone-multiple 3 Cases 166277 fractures-dentinogenesis 0.5 P* 902 Werner syndrome imperfecta-skeletal dysplasia 3.7 P* 6.0 P* 3465 Worster-Drought syndrome 3451 West syndrome 0.1 I* 3.7 BP 178475 Wound botulism 3451 West syndrome 30 Cases 3.5 BP* 2834 Wrinkly skin syndrome 3451 West syndrome 90 Cases 0.036 I* 53719 Wyburn-Mason syndrome 83476 West-Nile encephalitis 64747 X-linked Charcot-Marie-Tooth 1.6 P* 2475 White forelock with 2 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 90 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families disease chondrodysplasia punctata X-linked Charcot-Marie-Tooth 5 Cases X-linked dominant 101076 10 Cases disease type 2 163966 chondrodysplasia, Chassaing-

4 Lacombe type X-linked Charcot-Marie-Tooth 101077 Families X-linked dyserythropoietic disease type 3 1 Family 363727 anemia with abnormal platelets

X-linked Charcot-Marie-Tooth 7 Cases and neutropenia 101078 disease type 4 X-linked endothelial corneal 35 Cases 293621 X-linked Charcot-Marie-Tooth 9 Cases dystrophy 99014 disease type 5 X-linked erythropoietic 50 Cases 443197 X-linked Charcot-Marie-Tooth 8 Cases protoporphyria 352675 disease type 6 X-linked external auditory canal 2 atresia-dilated internal auditory 4 Cases 500188 75497 X-linked Ehlers-Danlos syndrome Families canal-facial dysmorphism

syndrome X-linked Emery-Dreifuss 1.0 BP X-linked female restricted facial 98863 dysmorphism-short stature- 17 Cases muscular dystrophy 480880 X-linked Emery-Dreifuss 1.0 P choanal atresia-intellectual 98863 muscular dystrophy disability X-linked hereditary sensory and 5 33 Cases 300373 X-linked acrogigantism 139583 autonomic neuropathy with Families

X-linked adrenal hypoplasia 8.0 BP deafness 95702 X-linked hypohidrotic ectodermal 0.75 BP* congenita 181 5.0 BP dysplasia 43 X-linked adrenoleukodystrophy 0.21 P* 89936 X-linked hypophosphatemia 5.0 BP* 43 X-linked adrenoleukodystrophy X-linked immunodeficiency with 7 Cases 0.1 P* 317476 magnesium defect, Epstein-Barr 47 X-linked agammaglobulinemia virus infection and neoplasia 0.22 P X-linked immunoneurologic 5 Cases 47 X-linked agammaglobulinemia 2571 disorder 1 Family X-linked intellectual disability 14 Cases 391327 X-linked calvarial hyperostosis 364028 due to GRIA3 mutations X-linked central congenital X-linked intellectual disability 2 27 Cases 329235 hypothyroidism with late-onset 67045 with isolated growth hormone Families

testicular enlargement deficiency 0.2 P* X-linked intellectual disability, 8 Cases 596 X-linked centronuclear myopathy 85273 Abidi type X-linked cerebral-cerebellar- 3 Cases X-linked intellectual disability, 6 Cases 163961 85276 coloboma syndrome Armfield type X-linked intellectual disability, 9 Cases X-linked colobomatous 3056 microphthalmia-microcephaly- 1 Family Brooks type 431140 24 intellectual disability-short X-linked intellectual disability, 85293 Families stature syndrome Cabezas type X-linked complicated corpus 11 Cases 1497 X-linked intellectual disability, 30 Cases callosum dysgenesis 85277 10 Cantagrel type X-linked cone dysfunction 90001 Families X-linked intellectual disability, 4 Cases syndrome with myopia 163971 Cilliers type 6 Cases X-linked intellectual disability, 3 Cases 1661 X-linked corneal dermoid 93947 Golabi-Ito-Hall type 150 X-linked intellectual disability, 9 Cases X-linked creatine transporter 93952 52503 Cases Hedera type deficiency X-linked intellectual disability, 4 Cases 85283 2 Miles-Carpenter type X-linked distal spinal muscular 35 139557 Families X-linked intellectual disability, atrophy type 3 163937 Families Najm type 35173 X-linked dominant 0.25 BP*

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 91 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families X-linked intellectual disability, 8 Cases global development delay-facial 163956 Nascimento type dysmorphism-sacral caudal X-linked intellectual disability, 1 Family remnant syndrome 85322 Pai type X-linked intellectual disability- X-linked intellectual disability, 4 Cases hypogammaglobulinemia- 3 Cases 85285 85317 Schimke type progressive neurological X-linked intellectual disability, 4 Cases deterioration syndrome 85323 X-linked intellectual disability- Seemanova type 4 Cases X-linked intellectual disability, 9 Cases 3055 hypogonadism-ichthyosis- 85286 Shashi type obesity-short stature syndrome X-linked intellectual disability- X-linked intellectual disability, 3 Cases 10 Cases 85324 85329 hypotonia-facial dysmorphism- Shrimpton type 2 aggressive behavior syndrome X-linked intellectual disability, X-linked intellectual disability- 85287 Families 38 Cases Siderius type 457260 hypotonia-movement disorder

X-linked intellectual disability, 21 Cases syndrome 3063 X-linked intellectual disability- Snyder type 2 Cases X-linked intellectual disability, 4 Cases 423479 limb spasticity-retinal dystrophy- 85325 Stevenson type diabetes insipidus syndrome X-linked intellectual disability- X-linked intellectual disability, 1 Family 12 Cases 85288 85320 macrocephaly-macroorchidism Stocco Dos Santos type syndrome X-linked intellectual disability, 4 Cases 85326 X-linked intellectual disability- 2 Cases Stoll type 2898 plagiocephaly syndrome X-linked intellectual disability, 7 Cases 163976 X-linked intellectual disability- Van Esch type 6 Cases 3077 psychosis-macroorchidism X-linked intellectual disability, 3 Cases 85290 syndrome Wilson type X-linked intellectual disability- 4 Cases X-linked intellectual disability- 3052 seizures-psoriasis syndrome Dandy-Walker malformation- 10 Cases 1568 X-linked intellectual disability- basal ganglia disease-seizures 20 Cases 457240 short stature-overweight syndrome syndrome X-linked intellectual disability- 2 Cases X-linked keloid scarring-reduced 85327 acromegaly-hyperactivity 15 Cases 482606 joint mobility-increased optic syndrome cup-to-disc ratio syndrome X-linked intellectual disability- 9 Cases 85338 6 ataxia-apraxia syndrome X-linked lethal multiple 79447 Families X-linked intellectual disability- pterygium syndrome 2 Cases 324410 cardiomegaly-congestive heart 30 failure syndrome X-linked lissencephaly with 452 Families 14 abnormal genitalia X-linked intellectual disability- 137831 Families cerebellar hypoplasia syndrome X-linked lymphoproliferative 0.05 P* 2442 disease X-linked intellectual disability- 2 Cases X-linked lymphoproliferative 100 459070 cerebellar hypoplasia-spondylo- 538931 disease due to SH2D1A Cases epiphyseal dysplasia syndrome deficiency X-linked intellectual disability- 9 Cases 163979 100 craniofacioskeletal syndrome X-linked lymphoproliferative 538934 Cases X-linked intellectual disability- disease due to XIAP deficiency 5 Cases 85280 cubitus valgus-dysmorphism X-linked mandibulofacial 7 Cases syndrome 1131 dysostosis X-linked intellectual disability- 8 Cases 2958 dysmorphism-cerebral atrophy X-linked mendelian susceptibility 13 Cases 319605 syndrome to mycobacterial diseases X-linked mendelian susceptibility X-linked intellectual disability- 7 Cases epilepsy-progressive joint 2 Cases 319623 to mycobacterial diseases due to 85319 contractures-dysmorphism CYBB deficiency X-linked mendelian susceptibility 6 Cases syndrome 319612 480907 X-linked intellectual disability- 14 Cases to mycobacterial diseases due to

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 92 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

Number Number of of Estimated Estimated ORPHACod Disease publishe ORPHACod Disease publishe prevalence/inciden prevalence/inciden e or Group of diseases d cases e or Group of diseases d cases ce (/100,000) ce (/100,000) or or families families IKBKG deficiency X-linked microcephaly-growth XY type gonadal dysgenesis- 2 Cases 3 Cases 1770 435938 retardation-prognathism- associated anomalies syndrome

cryptorchidism syndrome 2 Cases 370930 XYLT1-CDG 18 X-linked myopathy with 25980 Families 0.23 BP* excessive autophagy 910 Xeroderma pigmentosum

7 X-linked myopathy with postural 50 Cases 178461 Families 90342 Xeroderma pigmentosum variant muscle atrophy Xeroderma pigmentosum- 30 Cases X-linked myotubular myopathy- 4 Cases 220295 456328 Cockayne syndrome complex abnormal genitalia syndrome 100

X-linked neurodegenerative 7 Cases 261476 Xp21 deletion syndrome Cases 85334 syndrome, Bertini type X-linked neurodegenerative 11 Cases Xq12-q13.3 duplication 3 Cases 85336 314389 syndrome, Hamel type syndrome 3 X-linked non progressive 13 Cases 314978 Families 1435 Xq21 microdeletion syndrome cerebellar ataxia 28 Cases 8 521258 Xq25 microduplication syndrome X-linked osteoporosis with 391330 Families 8 Cases fractures 261483 Xq27.3q28 duplication syndrome

X-linked parkinsonism-spasticity 5 Cases 400 363654 syndrome 662 Yellow nail syndrome Cases X-linked recessive ocular 0.58 BP* 54 albinism Young adult-onset distal 3 Cases 6 314485 X-linked reticulate pigmentary hereditary motor neuropathy 85453 Families 15.0 P* disorder 2828 Young-onset Parkinson disease

8 Cases 25 Cases 1852 X-linked retinal dysplasia 3472 Yunis-Varon syndrome

5.0 P 10 Cases 792 X-linked retinoschisis 97240 Zebra body myopathy

4.5 P* 3 Cases 792 X-linked retinoschisis 217017 Zechi-Ceide syndrome

X-linked scapuloperoneal 22 Cases Zellweger-like syndrome without 2 Cases 431272 50812 muscular dystrophy peroxisomal anomalies X-linked severe congenital 45 Cases 52 Cases 86788 3473 Zimmermann-Laband syndrome neutropenia 200 0.15 I* 75563 X-linked sideroblastic anemia Cases 913 Zollinger-Ellison syndrome

0.125 I 5 913 Zollinger-Ellison syndrome X-linked sideroblastic anemia 2802 Families 5 and spinocerebellar ataxia 178333 Åland Islands eye disease Families X-linked skeletal dysplasia- 4 Cases 1436 intellectual disability syndrome X-linked spastic paraplegia type 1 Family 100997 16 X-linked spastic paraplegia type 24 Cases 171607 34 X-linked spasticity-intellectual 6 Cases 3175 disability-epilepsy syndrome X-linked spinocerebellar ataxia 5 Cases 85297 type 3 X-linked spinocerebellar ataxia 1 Family 85292 type 4 3469 XK aprosencephaly syndrome 10 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. P indicates prevalence data, I indicates incidence data and BP indicates birth prevalence Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2021 - 93 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

To access the complete Orphanet epidemiological data sets visit Orphadata (www.orphadata.org). For any questions or comments, please contact us: [email protected] Editor-in-chief : Ana Rath – Editor of the report : Annie Olry - Technical support : David Lagorce and Valérie Lanneau The correct form when quoting this document is : «Prevalence of rare diseases: Bibliographic data », Orphanet Report Series, Rare Diseases collection, January 2021, Number 1 : Diseases listed in alphabetical order http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf

This Orphanet Report Series is part of the Direct Grant N°831390 which has received funding from the European Union’s Health Program (2014-2020).

The content of this Orphanet Report Series represents the views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the Consumers, Health, Agriculture and Food Executive Agency or any other body of the European Union. The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.