Prevalence distribution of rare diseases 200 Orphanet Report Series 180 160 collection 140 Rare Diseases

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80 Number Number of diseases 60 May 2009 40 May 2010 Number 1

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0 0 5 10 15 20 25 30 35 40 45 50 Estimated prevalence (/100000)

Prevalence of rare diseases: Bibliographic data

Listed in alphabetical order of diseases

www.orpha.net

20091215 Methodology

A systematic survey of the literature is being Updated Data performed in order to provide an estimate of the New information from available data sources: EMA, prevalence of rare diseases in Europe. An updated new scientific publications, grey literature, expert report will be published regularly and will replace opinion. the previous version. This update contains new epidemiological data and modifications to existing data for which new information has been made Limitation of the study available. The exact prevalence rate of each rare disease is difficult to assess from the available data sources. Search strategy There is a low level of consistency between studies, a poor documentation of methods used, confusion The search strategy is carried out using several data between incidence and prevalence, and/or confusion sources: between incidence at birth and life-long incidence. - Websites: Orphanet, e-medicine, GeneClinics, EMA The validity of the published studies is taken for and OMIM ; granted and not assessed. It is likely that there - Medline is consulted using the search algorithm: is an overestimation for most diseases as the few «Disease names» AND Epidemiology[MeSH:NoExp] published prevalence surveys are usually done in OR Incidence[Title/abstract] OR Prevalence[Title/ regions of higher prevalence and are usually based abstract] OR Epidemiology[Title/abstract] ; on hospital data. Therefore, these estimates are an - Medical books, grey literature and reports from indication of the assumed prevalence but may not experts are also important sources of data. be accurate.

Collected data Prevalence values provided are the mean of the highest and lowest values collected. When prevalence is not documented we calculate it using incidence: - For congenital diseases with birth-onset, prevalence = incidence at birth x (patient life expectancy/ general population life expectancy) ; - For the other rare diseases, prevalence = incidence x rare disease mean duration ; When no prevalence or incidence data are available, the number of cases reported in the literature is provided. NB: Life expectancy of the French population (78 years) is used as the general population life expectancy.

For any questions or comments, please contact us: [email protected] Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Prevalence or reported number of published cases listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families 2,8 dihydroxyadenine urolithiasis 1,7 Acrocallosal syndrome, Schinzel type 34 cases 3C syndrome 25 cases Acrocephalosyndactyly 4,6 3-hydroxy 3-methylglutaryl-CoA synthase 6 cases Acrocraniofacial dysostosis 2 cases deficiency Acrodermatitis enteropathica, zinc 0,2 3M syndrome 40 cases deficiency type 3-methylcrotonylglycinuria 2,25 Acrofacial dysostosis, Catania type 6 cases 3-methylglutaconic aciduria type 1 20 cases Acrofacial dysostosis, Nager type 90 cases 3-methylglutaconic aciduria type 3 10 Acrofacial dysostosis, palagonia type 4 cases 46,XX disorder of sex development - 2 cases Acrofacial dysostosis, Rodriguez type < 10 cases skeletal anomalies Acro-fronto-facio-nasal dysostosis 5 cases 46,XX gonadal dysgenesis 12 Acromegaloid facial appearance syndrome < 20 cases 46,XY disorder of sex development - 2 cases Acromegaloid facies - hypertrichosis < 20 cases adrenal insufficiency Acromegaly 5 46,XY gonadal dysgenesis - motor and 6 cases sensory neuropathy Acromegaly - cutis verticis gyrata - 16 cases corneal leukoma 4-hydroxybutyricaciduria 350 cases Acromelanosis < 10 cases 5-oxoprolinase deficiency 8 cases Acromesomelic dysplasia, Brahimi-Bacha 3 cases 6-pyruvoyl-tetrahydropterin synthase 248 cases type deficiency Acromesomelic dysplasia, Hunter- 10 cases 6q terminal deletion 19 cases Thomson type Aarskog-Scott syndrome > 200 cases Acromesomelic dysplasia, Maroteaux type 50 cases Aase-Smith syndrome < 10 cases Acromicric dysplasia < 40 cases Ablepharon macrostomia syndrome 15 cases Acroosteolysis dominant type 50 cases Abruzzo-Erickson syndrome 4 cases Acro-pectoral syndrome 22 cases Absence of fingerprints - congenital milia 14 cases Acro-pectoro-renal field defect 12 cases Acalvaria < 1** Acropectorovertebral dysplasia < 30 cases Acanthamoeba keratitis 1 Acrorenal syndrome 20 cases Acatalasemia 3,1 Acro-renal-mandibular syndrome 7 cases Aceruloplasminemia 0,1 Acro-renal-ocular syndrome < 20 families Achalasia - microcephaly 5 cases Action myoclonus - renal failure syndrome 17 cases Acheiropodia < 10 families Acute bilateral depigmentation of the iris 5 cases Achondrogenesis > 100 cases Acute intermittent porphyria 10,1 Achondroplasia 4,5 Acute intermittent porphyria 10 Achromatopsia 3,33 Acute interstitial pneumonia 3,8 Ackerman syndrome 8 cases Acute lymphoblastic leukemia 6,5 Aconitase deficiency 19 cases Acute myeloid leukemia 12,1 Acquired epidermolysis bullosa 100 cases Acute myeloid leukemia 11,8 Acquired generalized lipodystrophy 80 cases Acute promyelocytic leukemia 8 Acquired hemophilia 0,1 Acute recurrent pancreatitis 10 Acquired hypertrichosis lanuginosa 60 cases Adamantinoma 513 cases Acquired Von Willebrand syndrome 300 cases

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 3 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Adducted thumbs - arthrogryposis, 3 families Alveolar echinococcosis < 1000 cases Christian type Amaurosis - hypertrichosis 2 cases Adducted thumbs-arthrogryposis, Dundar 5 cases Ambras syndrome 40 cases type Amelo-cerebro-hypohidrotic syndrome 19 cases Adenosine monophosphate deaminase 200 cases deficiency Aminopterin embryofetopathy 17 cases Adenylosuccinate lyase deficiency 50 cases Amniotic bands 4** Adrenocortical carcinoma 1 Amoebiasis due to free-living amoebae 1,75 Adult acute respiratory distress syndrome 30 Amyloidosis 30 Adult Still's disease 1,23 Amyotrophic lateral sclerosis 5,2 ADULT syndrome 14 cases Anaplastic large cell lymphoma 2 Agammaglobulinemia - microcephaly - 3 cases Anaplastic thyroid carcinoma 0,13 craniosynostosis - severe dermatitis ANE syndrome 5 cases Agenesis of the corpus callosum 2 cases Anencephaly 3,2** - intellectual deficit - coloboma - micrognathia Angelman syndrome 6,5 Agnathia - holoprosencephaly - situs 30 cases Angel-shaped phalango-epiphyseal 15 cases inversus dysplasia Agonadism - dextrocardia - diaphragmatic 6 cases Angio-osteohypertrophic syndrome 1000 cases hernia Anhidrotic ectodermal dysplasia 2 cases Aicardi syndrome 200 cases - immunodeficiency - osteopetrosis - lymphedema Aicardi-Goutieres syndrome 120 cases Aniridia 1,75 Alagille syndrome 1,4 Aniridia - absent patella 3 cases Alar cartilages hypoplasia - coloboma - 2 cases telecanthus Aniridia - cerebellar ataxia - mental > 10 families deficiency Albers-Schönberg osteopetrosis 1 Aniridia - ptosis - intellectual deficit - 3 cases Albinism ocular - late onset sensorineural 7 cases familial obesity deafness Aniridia - renal agenesis - psychomotor 2 cases Albinism-deafness syndrome 1 family retardation Albright hereditary osteodystrophy 0,72 Aniridia-intellectual deficit syndrome 2 cases Alexander disease 300 cases Anisakiasis 3,8 Al-Gazali-Dattani syndrome 3 cases Ankyloblepharon - ectodermal defects - 8 families Alkaptonuria 0,3 cleft lip palate Allan-Herndon-Dudley syndrome 89 cases Ankyloblepharon filiforme - imperforate 2 families anus Alopecia - congenita keratosis 1 family palmoplantaris Ankylosing vertebral hyperostosis with 8 cases tylosis Alopecia - contractures - dwarfism - 5 cases intellectual deficit Anomaly of bile acid synthesis 0,6 Alopecia- epilepsy - pyorrhea - mental 12 cases Anonychia - onychodystrophy with 11 cases subnormality hypoplasia or absence of distal phalanges Alopecia totalis 10,5 Anonychia microcephaly 5 cases Alopecia universalis 25 Anonychia with flexural pigmentation 3 cases Alpers syndrome 0,025 Anophthalmia - hypothalamo-pituitary 30 cases insufficiency Alpha thalassemia - intellectual deficit, 168 cases X-linked Anophthalmia - megalocornea - 3 cases cardiopathy - skeletal anomalies Alpha-1 antitrypsin deficiency 25 Anophthalmia plus syndrome 4 cases Alpha-mannosidosis 0,1 Anophthalmia/microphthalmia - 14 cases Alpha-N-acetylgalactosaminidase 12 cases esophageal atresia deficiency Antecubital pterygium syndrome 11 cases Alport syndrome 2 Antisynthetase syndrome 1,5 Alström syndrome 300 cases

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 4 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Antley-Bixler syndrome 34 cases Athabaskan brainstem dysgenesis 10 cases syndrome Antley-Bixler-like syndrome - ambiguous < 50 cases genitalia - disordered steroidogenesis Atherosclerosis- deafness - diabetes - 2 cases epilepsy - nephropathy Aortic aneurysm syndrome, Loeys-Dietz 10 families type Atkin-Flaitz syndrome 14 cases Aortic arch anomaly - peculiar facies - 4 cases Atopic keratoconjunctivitis 15,1 intellectual deficit Atransferrinemia 9 cases Aortic arch interruption 0,3** Atresia of small intestine 20 Aortic dilatation - joint hypermobility - 22 cases Atrial septal defect - atrioventricular 11 cases arterial tortuosity conduction defects Aorto-ventricular tunnel 130 cases Atrial tachyarrhythmia with short PR 12 cases Apert syndrome 1,25 interval Aphalangy - hemivertebrae - urogenital- 3 cases Atypical coarctation of aorta 0,17** intestinal dysgenesis Atypical hemolytic uremic syndrome 1 Aphalangy - syndactyly - microcephaly 1 family Atypical Rett syndrome 2,22 Aplasia cutis - myopia 4 cases Auricular abnormalities - cleft lip 2 cases Aplasia cutis congenita - intestinal 3 cases with or without cleft palate - ocular lymphangiectasia abnormalities Aplasia cutis congenita of limbs recessive 6 cases Auriculoocular anomalies - cleft lip 2 cases Apnea of prematurity 8,5 Auriculoosteodysplasia 2 families Arachnodactyly - intellectual deficit - 3 cases Autism 45 dysmorphism Autism - facial port-wine stain 4 cases Arachnodactyly - ossification abnormal - 5 cases Autoimmune lymphoproliferative 100 cases intellectual deficit syndrome AREDYLD syndrome 3 cases Autosomal dominant acute necrotizing 11 cases Argininemia 31 cases encephalopathy Arhinia - choanal atresia - 4 cases Autosomal dominant cerebellar ataxia 2,15 microphthalmia Autosomal dominant Charcot-Marie-Tooth 1 family Aromatase deficiency 13 cases disease type 2F Arrhinia 20 cases Autosomal dominant Charcot-Marie-Tooth 1 family disease type 2G Arrhythmogenic right ventricular 43,5 dysplasia Autosomal dominant Charcot-Marie-Tooth 3 families disease type 2K Arterial dissection - lentiginosis 4 cases Autosomal dominant Charcot-Marie-Tooth 1 family Arterial tortuosity syndrome < 80 cases disease type 2L Arthrogryposis - hyperkeratosis, lethal 2 cases Autosomal dominant craniodiaphyseal 2 cases form dysplasia Arthrogryposis - renal dysfunction - < 100 cases Autosomal dominant diffuse palmoplantar 2,5 cholestasis keratoderma, Norrbotten type Arthrogryposis multiplex congenita 30 Autosomal dominant familial hematuria - 8 cases Arthrogryposis multiplex congenita - 10 cases retinal arteriolar tortuosity - contractures whistling face Autosomal dominant hyper IgE syndrome 250 cases Arthrogryposis-like hand anomaly - 1 family Autosomal dominant hypohidrotic 40 cases sensorineural deafness ectodermal dysplasia Ascher syndrome 50 cases Autosomal dominant limb-girdle muscular 2 families Astley-Kendall dysplasia 5 cases dystrophy type 1A Ataxia-deafness-retardation syndrome 8 cases Autosomal dominant limb-girdle muscular 5 families Ataxia-telangiectasia 1 dystrophy type 1D Atelosteogenesis I 12 cases Autosomal dominant limb-girdle muscular 5 families dystrophy type 1E Atelosteogenesis type II 25 cases Autosomal dominant limb-girdle muscular 1 family Atelosteogenesis type III 12 cases dystrophy type 1F

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 5 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Autosomal dominant limb-girdle muscular 1 family Autosomal recessive limb-girdle muscular 0,57 dystrophy type 1G dystrophy type 2E Autosomal dominant 5 cases Autosomal recessive limb-girdle muscular 0,57 macrothrombocytopenia with abnormal dystrophy type 2F proplatelet formation Autosomal recessive limb-girdle muscular 14 cases Autosomal dominant medullary 0,11 dystrophy type 2G cystic kidney disease with or without Autosomal recessive limb-girdle muscular > 40 families hyperuricemia dystrophy type 2I Autosomal dominant multiple pterygium 4 cases Autosomal recessive malignant 0,75** syndrome osteopetrosis Autosomal dominant optic atrophy and 14 cases Autosomal recessive medullary cystic 1,05 cataract kidney disease Autosomal dominant osteopetrosis type 1 33 cases Autosomal recessive polycystic kidney 6,5 Autosomal dominant polycystic kidney 30 cases disease disease type 1 with tuberous sclerosis Autosomal recessive spastic paraplegia 1 family Autosomal dominant pterygium popliteal 0,3 type 14 syndrome Autosomal recessive spastic paraplegia < 10 families Autosomal dominant severe congenital 0,4** type 15 neutropenia Autosomal recessive spastic paraplegia 1 family Autosomal dominant spastic paraplegia < 10 families type 23 type 10 Autosomal recessive spastic paraplegia 1 family Autosomal dominant spastic paraplegia < 10 families type 24 type 12 Autosomal recessive spastic paraplegia 1 family Autosomal dominant spastic paraplegia < 10 families type 25 type 13 Autosomal recessive spastic paraplegia 2 families Autosomal dominant spastic paraplegia < 20 families type 26 type 17 Autosomal recessive spastic paraplegia 2 families Autosomal dominant spastic paraplegia 1 family type 27 type 29 Autosomal recessive spastic paraplegia 1 family Autosomal dominant spastic paraplegia 13 cases type 28 type 37 Autosomal recessive spastic paraplegia 1 family Autosomal dominant spastic paraplegia 1 family type 30 type 38 Autosomal recessive spastic paraplegia 1 family Autosomal dominant spastic paraplegia 10 families type 32 type 6 Autosomal recessive spastic paraplegia 1 family Autosomal dominant spastic paraplegia < 10 families type 35 type 8 Autosomal recessive spastic paraplegia 2 families Autosomal dominant spastic paraplegia 1 family type 39 type 9 Axenfeld-Rieger anomaly - hydrocephaly - 3 cases Autosomal recessive acrofacial dysostosis 2 cases skeletal abnormalities Autosomal recessive amelia 3 cases Axial spondylometaphyseal dysplasia 3 cases Autosomal recessive ataxia, Beauce type 57 cases Babesiosis 40 cases Autosomal recessive cerebellar ataxia 7 Bacterial toxic-shock syndrome 3 Autosomal recessive cerebellar ataxia - 3 families Bakrania-Ragge syndrome 2 families blindness - deafness Ballard syndrome 12 cases Autosomal recessive cerebellar ataxia - 1 family Bamforth syndrome 5 cases saccadic intrusion Bangstad syndrome 2 cases Autosomal recessive limb girdle muscular 3,8 dystrophy type 2A Banki syndrome 1 family Autosomal recessive limb-girdle muscular 1,96 Barber-Say syndrome 10 cases dystrophy type 2C Bardet-Biedl syndrome 0,8 Autosomal recessive limb-girdle muscular 0,57 Bartsocas-Papas syndrome 24 cases dystrophy type 2D Bartter syndrome 0,12

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 6 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Bazex syndrome 145 cases Boutonneuse fever 17 Bazex-Dupre-Christol syndrome 143 cases Bowen-Conradi syndrome 44 cases Beckwith-Wiedemann syndrome 7,3 Brachydactyly - arterial hypertension > 10 families Beemer-Ertbruggen syndrome 2 cases Brachydactyly - long thumb 4 cases Behcet disease 2,5 Brachydactyly - nystagmus - cerebellar 1 family ataxia Bencze syndrome 2 families Brachydactyly - preaxial hallux varus 8 cases Benign exophthalmos syndrome 4 cases Brachydactyly type A5 2 families Benign familial neonatal-infantile 10 families seizures Brachydactyly type A7 1 family Benign paroxysmal torticollis of infancy 50 cases Brachymorphism - onychodysplasia - 9 cases dysphalangism Berant syndrome 1 family Brachytelephalangy - dysmorphism - 2 cases Berardinelli-Seip congenital lipodystrophy 0,25 Kallmann syndrome Bernard-Soulier syndrome 100 cases Braddock syndrome 2 cases Best disease 4,4 Bradyopsia 5 cases Beta-mannosidosis 14 cases Brain demyelination due to methionine 2 cases Beta-thalassemia 0,5 adenosyltransferase deficiency Beta-ureidopropionase deficiency 5 cases Brain malformation - congenital heart 2 cases Bethlem myopathy 100 cases disease - postaxial polydactyly Bickel-Fanconi glycogenosis 112 cases Branchiogenic deafness syndrome 5 cases Bilateral anorchidia 2,5 Branchio-oculo-facial syndrome < 50 cases Bilateral microtia - deafness - cleft palate 4 cases Branchio-skeleto-genital syndrome 3 cases Bilateral renal agenesis 17 Bronchopulmonary dysplasia 13 Bilateral striopallidodentate calcinosis < 200 cases Brown-Vialetto-van Laere syndrome < 100 cases Biliary atresia 5,6 Bruck syndrome < 40 cases Biliary tract malformation - renal failure 6 cases Brugada syndrome 20 Birt-Hogg-Dube syndrome 0,5 Budd-Chiari syndrome 1,5 Björnstad syndrome 33 cases Buerger's disease 12,5 Blackfan-Diamond disease 0,32 Bullous dystrophy, macular type 2 families Bleeding diathesis due to glycoprotein < 20 cases Bullous pemphigoid 2,5 VI deficiency or integrin alpha2-beta1 Buschke-Ollendorff syndrome 5 deficiency Buttiens-Fryns syndrome 3 cases Blepharo-cheilo-odontic syndrome < 50 cases Cabezas syndrome 1 family Blepharo-facio-skeletal syndrome 2 cases CACH syndrome 148 cases Blepharonasofacial malformation 2 families CADASIL syndrome 500 cases syndrome Calvarial doughnut lesions - bone fragility 20 cases Blepharophimosis - ptosis - esotropia - 6 cases syndactyly - short stature CAMOS syndrome 5 cases Blepharoptosis - myopia - ectopia lentis 3 cases Campomelia, Cumming type 8 cases Blindness - scoliosis - arachnodactyly 4 cases Campomelic dysplasia 0,35 Bloom syndrome > 100 cases Camptobrachydactyly 1 family Blue rubber bleb nevus > 200 cases Camptodactyly - fibrous tissue 3 cases hyperplasia - skeletal dysplasia Bone tumor 10 Camptodactyly - tall stature - scoliosis - 30 cases Bonnemann-Meinecke-Reich syndrome 4 cases hearing loss Book syndrome 25 cases Camptodactyly - taurinuria 4 families Boomerang dysplasia 10 cases Camptodactyly syndrome, Guadalajara 8 cases BOR syndrome 2,5 type 1 Bosley-Salih-Alorainy syndrome 9 cases Camptodactyly syndrome, Guadalajara 2 cases Botulism 0,05 type 2

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 7 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Camurati-Engelmann disease 200 cases CDG syndrome type Ib 20 cases Cantrell pentalogy 0,55** CDG syndrome type Ic > 30 cases Cantu syndrome 23 cases CDG syndrome type Id 5 cases Cap myopathy < 10 cases CDG syndrome type Ie 7 cases Cap polyposis 20 cases CDG syndrome type If 4 cases Capillary leak syndrome 57 cases CDG syndrome type Ig 6 cases Capra-DeMarco syndrome 4 cases CDG syndrome type Ih 5 cases Carbamoylphosphate synthetase 0,7 CDG syndrome type IIa 4 cases deficiency CDG syndrome type IIe 2 cases Carcinoma of the gallbladder 6,5 CDG syndrome type IIh 2 cases Cardiac anomalies - heterotaxy 9 cases CDG syndrome type Ik 4 cases Cardiac anomalies - heterotaxy 9 cases CDG syndrome type IL 2 cases Cardiac conduction disease - dilated 10 cases CEDNIK syndrome 7 cases cardiomyopathy - brachydactyly Celiac disease - epilepsy - occipital 170 cases Cardiocranial syndrome, Pfeiffer type < 10 cases calcifications Cardiomyopathy - cataract - hip spine 9 cases Central areolar choroidal dystrophy 3,33 disease Central neurocytoma > 100 cases Cardiomyopathy - renal anomalies 2 cases Cerebellar ataxia - areflexia - pes cavus - 2 families Cardiomyopathy-exercise intolerance due 3 cases optic atrophy - sensorineural hearing loss to muscle and heart glycogen deficiency Cerebral arteriovenous fistula 6 Carey-Fineman-Ziter syndrome < 20 cases Cerebral gigantism - jaw cysts < 10 cases Carney complex 160 cases Cerebro-costo-mandibular syndrome 60 cases Carney triad 100 cases Cerebro-oculo-nasal syndrome 10 cases Carnitine palmitoyl transferase 1 35 cases deficiency Cerebroretinal vasculopathy 3 families Carnitine palmitoyl transferase 2 > 100 cases Cervical hypertrichosis - peripheral 3 cases deficiency neuropathy Carnitine-acylcarnitine translocase 30 cases CHAND syndrome > 10 cases deficiency Chaotic atrial tachycardia 100 cases Carnosinemia 30 cases Char syndrome 10 cases Caroli disease < 250 cases Charcot-Marie-Tooth disease 32,5 Carpenter syndrome 40 cases Charcot-Marie-Tooth disease - 10 cases Carpotarsal osteochondromatosis < 10 cases nephropathy Castleman disease 400 cases Charcot-Marie-Tooth disease type 2B2 1 family Cataract - ataxia - deafness 2 cases Charcot-Marie-Tooth disease type 2H 13 cases Cataract - deafness - hypogonadism 3 cases Charcot-Marie-Tooth disease type 4B1 11 families Cataract - intellectual deficit - 10 cases Charcot-Marie-Tooth disease type 4H 10 cases hypogonadism Charcot-Marie-Tooth disease type 4J 5 cases Cataract - nephropathy - encephalopathy 2 cases CHARGE syndrome 0,14 Cataract cardiomyopathy 30 cases Chediak-Higashi syndrome > 10 cases Cataract-glaucoma 3 families CHILD syndrome 30 cases Cataract-microcornea syndrome 8 families Childhood disintegrative disorder 2 Catecholinergic polymorphic ventricular 10 Choanal atresia 8,2 tachycardia Choanal atresia - deafness - cardiac 5 cases Catel-Manzke syndrome 27 cases defects - dysmorphism Cat-eye syndrome 1,35 Cholangiocarcinoma 10 Cat-scratch disease 6,6 Cholestasis - lymphedema 50 cases CDG syndrome 1,5** Cholestasis pigmentary - retinopathy - 5 cases CDG syndrome type Ia 300 cases cleft palate

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 8 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Cholesteryl ester storage disease < 50 cases Cogan syndrome 200 cases Chondrodysplasia - disorder of sex 2 cases Cohen syndrome 100 cases development Cold-induced sweating syndrome 6 cases Chondrodysplasia punctata, rhizomelic 1 Cole-Carpenter syndrome 4 cases type Collagenous colitis 10,5 Chondrodysplasia, Blomstrand type 13 cases Coloboma of macula - brachydactyly 12 cases Chordoma 0,05 type B Choroidal atrophy - alopecia 2 cases Coloboma uveal - cleft lip palate - 12 cases Choroideremia 2 intellectual deficit Choroideremia - deafness - obesity 4 cases Colobomatous - microphthalmia - heart 10 cases disease - hearing loss Christ-Siemens-Touraine syndrome 0,35 Combined deficiency of factor V and 0,5 Chronic autoimmune hepatitis 0,75 factor VIII Chronic B-cell lymphocytic leukemia 32 Common variable immunodeficiency 7,5 Chronic bronchopneumopathy due to TAP < 20 cases Complete atrioventricular canal 15** deficiency Cone rod dystrophy 2,5 Chronic granulomatous disease 0,2 Congenital adrenal hyperplasia 10 Chronic hepatic porphyria 1,5 Congenital analbuminemia < 50 cases Chronic hiccup 1 Congenital bilateral absence of vas 50 Chronic inflammatory demyelinating 4,4 deferens polyneuropathy Congenital bile acid synthesis defect 4 cases Chronic myeloid leukemia 6 type 4 Churg-Strauss syndrome 1 Congenital brain dysgenesis due to 2 cases Chylomicron retention disease 40 cases glutamine synthetase deficiency CINCA syndrome 100 cases Congenital bronchobiliary fistula 23 cases Circumscribed palmoplantar hypokeratosis 17 cases Congenital bullous ichthyosiform 0,4 CLAPO syndrome 6 cases erythroderma Classic Ehlers-Danlos syndrome 3,5 Congenital cataracts - facial dysmorphism 100 cases - neuropathy Cleft lip - retinopathy 2 cases Congenital diaphragmatic hernia 15 Cleft lip/palate - intellectual deficit - 2 cases corneal opacities Congenital dyserythropoietic anemia 1 Cleft lip/palate - intestinal malrotation - 4 cases Congenital enterocyte heparan sulfate 3 cases cardiopathy deficiency Cleft palate 50 Congenital erythropoietic porphyria > 200 cases Cleft palate - cardiac defect - genital 5 cases Congenital factor II deficiency 0,05 anomalies - ectrodactyly Congenital factor V deficiency 0,1 Cleft palate - short stature - vertebral 2 cases Congenital factor VII deficiency 0,25 anomalies Congenital factor X deficiency 0,2 Cleft palate - stapes fixation - oligodontia 2 cases Congenital factor XI deficiency 0,1 Cleft palate-lateral synechia syndrome 7 cases Congenital factor XIII deficiency 0,5 Cleido rhizomelic syndrome 2 cases Congenital fibrinogen deficiency 0,15 Clouston syndrome 1 Congenital hypothyroidism 29 COACH syndrome 8 cases Congenital ichthyosis - microcephalus - 2 cases Coats disease 2 quadriplegia Cobb syndrome 35 cases Congenital insensitivity to pain 20 cases Cockayne syndrome 200 cases Congenital intrauterine infection-like > 30 cases CODAS syndrome 3 cases syndrome Coffin-Lowry syndrome 0,55 Congenital Leber amaurosis 10 Coffin-Siris syndrome 40 cases Congenital lethal erythroderma 17 cases COFS syndrome < 20 cases Congenital lobar emphysema 4,5

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 9 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Congenital lymphedema 8,8 Craniofrontonasal dysplasia, Teebi type 20 cases Congenital malabsorptive diarrhea due to 3 cases Craniolenticulosutural dysplasia 28 cases paucity of enteroendocrine cells Craniometaphyseal dysplasia 70 cases Congenital megacalycosis > 50 cases Craniopharyngioma 2 Congenital muscular dystrophy 5 Craniorachischisis 5 Congenital muscular dystrophy due to 15 cases Craniorhiny 3 families lamine A/C deficiency Craniosynostosis - Dandy-Walker - 4 cases Congenital muscular dystrophy type 1A 0,3 hydrocephalus Congenital muscular dystrophy with 0,03 Craniosynostosis - dysmorphism - 5 cases integrin deficiency brachydactyly Congenital muscular dystrophy, Ullrich < 100 cases Craniosynostosis - fibular aplasia 2 cases type Craniosynostosis - intracranial 3 cases Congenital myasthenic syndromes 0,75 calcifications Congenital osteogenesis imperfecta - 3 cases Craniosynostosis, Boston type 19 cases microcephaly - cataracts Craniosynostosis, Philadelphia type 1 family Congenital pseudoarthrosis of clavicle > 200 cases Craniosynostosis-radial aplasia, Imaizumi 2 cases Congenital pulmonary lymphangiectasia > 100 cases type Congenital pulmonary valve stenosis 7,2 Creutzfeldt-Jakob disease 0,1 Congenital Rubella syndrome 1** Crigler-Najjar syndrome 1 Congenital sucrase-isomaltase deficiency 20 Crisponi syndrome < 30 cases Congenital toxoplasmosis 50 Criss-cross heart 0,8 Congenitally short costocoracoid ligament 1 family Cronkhite-Canada syndrome 500 cases Contractures - ectodermal dysplasia - 2 cases Crouzon disease 2 cleft lip/palate Cryptomicrotia - brachydactyly - excess 2 cases Cooper-Jabs syndrome 2 cases fingertip arch Corneal anesthesia - deafness - 2 cases Cryptosporidiosis 34 intellectual deficit Curry-Jones syndrome 5 cases Corneal dystrophy - perceptive deafness < 10 cases Cushing disease 4 Corneal-cerebellar syndrome 2 cases Cushing syndrome 5,9 Cornelia de Lange syndrome 1,9 Cutaneous lupus erythematosus 50 Coronary artery disease - hyperlipidemia - 1 family hypertension - diabetes - osteoporosis Cutaneous lymphoma 8,3 Corpus callosum agenesis neuronopathy 19 Cutaneous mastocytosis 0,75 Cortical blindness - intellectual deficit - 3 cases Cutaneous neuroendocrine carcinoma 0,5 polydactyly Cutaneous photosensitivity - lethal colitis 3 cases Corticobasal degeneration 4 Cutaneous T-cell lymphoma 14,9 Corticosteroid-sensitive aseptic abscesses 49 cases Cutis gyrata - acanthosis nigricans - 6 cases Costello syndrome 200 cases craniosynostosis Cowden syndrome 0,45 Cutis laxa > 100 cases Coxoauricular syndrome 4 cases Cutis marmorata telangiectatica 300 cases congenita Coxo-podo-patellar syndrome 47 cases Cutis verticis gyrata - intellectual deficit 1,02 Cranio osteoarthropathy 4 cases Cyprus facial-neuromusculoskeletal 1 family Craniodiaphyseal dysplasia > 20 cases syndrome Craniodigital syndrome - intellectual 5 cases Cystathioninuria 7 deficit Cystic fibrosis 12 Craniofacial conodysplasia 1 family Cystic hamartoma of lung and kidney < 5 cases Craniofacial dyssynostosis 0,05 Cystinosis 0,5 Craniofacial-deafness-hand syndrome 3 cases Cystinuria 14 Craniofrontonasal dysplasia - Poland 3 cases anomaly Cystoid macular dystrophy 6 families

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 10 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Cytophagic histiocytic panniculitis < 100 cases Developmental delay due to < 30 cases 2-methylbutyryl-CoA dehydrogenase Czech dysplasia, metatarsal type < 20 cases deficiency Dacryocystitis - osteopoikilosis 5 cases Developmental malformations - deafness 2 cases Dahlberg-Borer-Newcomer syndrome 2 cases - dystonia Dandy-Walker malformation - postaxial 2 cases Diabetes - maternally inherited deafness 0,1 polydactyly Diaphanospondylodysostosis < 10 cases Darier disease 1,5 Diaphragmatic defect - limb deficiency - 4 cases Deaf blind hypopigmentation syndrome, 2 cases skull defect Yemenite type Diastrophic dwarfism 1,2 Deafness - enamel hypoplasia - nail 6 cases Diffuse large B-cell lymphoma 20 defects Diffuse neonatal hemangiomatosis < 70 cases Deafness - genital anomalies - metacarpal 2 cases and metatarsal synostosis Diffuse palmoplantar keratoderma - 10 cases acrocyanosis Deafness - lymphedema - leukemia < 10 cases Digitorenocerebral syndrome < 10 cases Deafness - opticoacoustic nerve atrophy 3 cases - dementia Digitotalar dysmorphism 6 Deafness - peripheral neuropathy - 4 cases Dihydropteridine reductase deficiency 134 cases arterial disease Dihydropyrimidinuria 7 cases Deafness - skeletal dysplasia - lip 8 cases Dincsoy-Salih-Patel syndrome 2 cases granuloma Dirofilariasis 25 cases Deafness - vitiligo - achalasia 2 cases Disorder of sex development - intellectual 3 cases Deafness-infertility syndrome 3 families deficit Deafness-intellectual deficit, Martin- 3 cases Disseminated peritoneal leiomyomatosis 100 cases Probst type Distal asymmetrical inflammatory 10 cases Deafness-intellectual deficit, Martin- 3 cases myopathy of the upper limbs Probst type Distal monosomy 10q 40 cases Deafness-tubular acidosis-anemia 2 cases Distal monosomy 5q 10 cases Dehydratase deficiency 21 cases Distal monosomy 8p 20 cases Deletion 2p21 7 cases Distal myopathy with early respiratory 24 cases Deletion 2q24 23 cases muscle involvement Deletion 2q37 10 cases Distal myopathy with posterior leg and 12 cases Deletion 6q16 syndrome 7 cases anterior upper limb involvement DEND syndrome 14 cases Distal myopathy with vocal cord 12 cases weakness Dentatorubral pallidoluysian atrophy < 0,3 Distal myopathy, Nonaka type 0,1 Dentinogenesis imperfecta - short stature 2 cases - hearing loss - intellectual deficit Distal myopathy, Welander type 10 Denys-Drash syndrome 150 cases Distal symphalangism < 5 families Dermatitis herpetiformis 20,2 Distal trisomy 10q 40 cases Dermato-cardio-skeletal syndrome, 2 cases Distal trisomy 6p 40 cases Borrone type Donnai-Barrow syndrome 13 cases Dermatofibrosarcoma protuberans 10 DOOR syndrome < 50 cases Dermatoleukodystrophy 2 cases Dopamine beta-hydroxylase deficiency 12 cases Dermatomyositis 14,8 Dopa-responsive dystonia 0,3 Dermatoosteolysis, Kirghizian type 5 cases Double outlet left ventricle 32 cases Dermo-odonto dysplasia 14 cases Double uterus - hemivagina - renal < 60 cases Desbuquois syndrome > 40 cases agenesis Desmosterolosis 2 cases Duane anomaly - myopathy - scoliosis 2 cases Developmental delay - deafness, 1 family Duane syndrome 10 Hildebrand type Dubowitz syndrome 150 cases Duchenne and Becker muscular dystrophy 5

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 11 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Duodenal atresia 8,55 Endosteal sclerosis - cerebellar hypoplasia 4 cases Dyggve-Melchior-Clausen disease 60 cases Eng-Strom syndrome 2 cases Dyschondrosteosis - nephritis 1 family Enteropancreatic endocrine tumor 14 Dyskeratosis congenita 0,1 Enthesitis-related arthritis 5,7 Dysmorphism - short stature - deafness - 2 cases Eosinophilic fasciitis 200 cases disorder of sex development Eosinophilic gastroenteritis 280 cases Dystrophic epidermolysis bullosa 5 Epidermal nevus syndrome > 400 cases Dystrophic epidermolysis bullosa 0,27 Epidermolysis bullosa simplex - limb < 20 cases Early infantile epileptic encephalopathy 88 cases girdle muscular dystrophy Early myoclonic encephalopathy 30 cases Epidermolytic epidermolysis bullosa 2,5 Early onset torsion dystonia 0,4 Epilepsy - microcephaly - skeletal 2 cases dysplasia Early-onset autosomal dominant 5,3 Alzheimer disease Epilepsy telangiectasia 6 cases Ear-patella-short stature syndrome 42 cases Epiphyseal dysplasia multiple 5 Ebstein malformation 1,25 Episodic ataxia type 3 1 family Ectodermal dysplasia - absent < 30 cases Episodic ataxia type 4 2 families dermatoglyphs Epithelio-exfoliative colitis - deafness 2 cases Ectodermal dysplasia - blindness 2 cases Erdheim-Chester disease 178 cases Ectodermal dysplasia - skin fragility 10 cases Ermine phenotype 3 cases syndrome Erythrokeratodermia ataxia 25 cases Ectodermal dysplasia, Berlin type 4 cases Erythrokeratodermia variabilis, Mendes da > 200 cases Ectodermal dysplasia, ''pure'' hair-nail < 20 cases Costa type type Erythropoietic protoporphyria 0,9 Ectopia lentis - chorioretinal dystrophy 4 cases - myopia Esophageal atresia 25 Ectrodactyly - ectodermal dysplasia 5 cases Esophageal carcinoma 8 without clefting Essential thrombocythemia 24 EEM syndrome 7 families Esthesioneuroblastoma < 1000 cases Ehlers-Danlos syndrome type 10 1 family Ethylmalonic encephalopathy < 40 cases Ehlers-Danlos syndrome type 3 12,5 Evans syndrome 0,1 Ehlers-Danlos syndrome type 4 1 Ewing sarcoma 0,1 Ehlers-Danlos syndrome type 5 2 families Excessive growth - learning disabilities - 6 families Ehlers-Danlos syndrome type 7C 7 cases facial dysmorphism Ehlers-Danlos syndrome, spondylocheiro 6 cases Eyebrow duplication - syndactyly 3 cases dysplastic type Fabry disease 1,75 Ehrlichiosis < 50 cases Facial dysmorphism - macrocephaly - 3 cases Eiken syndrome 6 cases myopia - Dandy-Walker malformation Elejalde disease 30 cases Facial onset sensory and motor 4 cases neuronopathy Ellis Van Creveld syndrome 150 cases Facioscapulohumeral muscular myopathy 7 Emery-Dreifuss muscular dystrophy 0,3 Familial adenomatous polyposis 5,25 Encephalocraniocutaneous lipomatosis 45 cases Familial amyloid polyneuropathy 1,1 Encephalopathy due to GLUT1 deficiency 84 cases Familial caudal dysgenesis 4 cases Encephalopathy due to < 30 cases hydroxykynureninuria Familial cold urticaria 0,1 Encephalopathy due to prosaposin < 10 cases Familial developmental dysphasia 6 families deficiency Familial dysautonomia 550 cases Encephalopathy due to sulfite oxidase 50 cases Familial encephalopathy with neuroserpin > 5 families deficiency inclusion bodies Enchondromatosis 600 cases Familial glucocorticoid deficiency 50 cases Endocrine tumor 1

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 12 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Familial isolated dilated cardiomyopathy 17,5 Follicular lymphoma 36 Familial isolated hypoparathyroidism < 10 families Foveal hypoplasia - presenile cataract 11 cases Familial isolated hypoparathyroidism due 2 families Fragile X syndrome 14,25 to agenesis of parathyroid gland Frank-Ter Haar syndrome 5 cases Familial isolated restrictive 2,5 Fraser syndrome 150 cases cardiomyopathy Freeman-Sheldon syndrome 100 cases Familial long QT syndrome 25 Fried syndrome 1 family Familial melanoma 46,8 Friedreich ataxia 2,5 Familial multiple fibrofolliculoma 7 cases Frontometaphyseal dysplasia < 30 cases Familial or sporadic hemiplegic migraine 10 Frontotemporal dementia 3 Familial Parkinson's disease dementia 41 Fronto-temporal dementia and 50 cases Familial partial lipodystrophy associated 10 cases parkinsonism linked to chromosome 17 with PPARG mutations Fructose intolerance 5 Familial partial lipodystrophy due to 1 family AKT2 mutations Fructose-1,6-bisphosphatase deficiency 2,5 Familial partial lipodystrophy, Dunnigan 300 cases Fryns syndrome 7** type Fucosidosis 100 cases Familial platelet syndrome with < 20 families Fuhrmann syndrome 11 cases predisposition to acute myelogenous leukemia Fumaric aciduria > 20 cases Familial platelet syndrome with 13 families Fuqua-Berkovitz syndrome 2 cases predisposition to acute myelogenous Galactosemia 6,6 leukemia Galloway-Mowat syndrome 40 cases Familial scaphocephaly syndrome, 11 cases McGillivray type Gamma aminobutyric acid transaminase 2 cases deficiency Familial spastic paraplegia 5 Gamma-glutamyl transpeptidase 7 cases Fanconi anemia 1 deficiency Fanconi ichthyosis dysmorphism 6 cases Gamma-glutamylcysteine synthetase 9 cases Fatal familial insomnia 27 cases deficiency Fatal mitochondrial disease due to 2 cases GAPO syndrome 27 cases combined oxidative phosphorylation Gardner-Morrison-Abbott syndrome 3 cases deficiency 3 Gastric cancer 20 Femur bifid - monodactylous ectrodactyly 200 cases Gastrointestinal stromal tumor 13 Femur-fibula-ulna complex 1,5 Gastroschisis 12 Fetal cytomegalovirus syndrome 40 Gaucher disease 2 Fetal methylmercury syndrome 800 cases Gaucher disease - ophthalmoplegia - < 10 cases Fetal varicella syndrome > 100 cases cardiovascular calcification Fibrochondrogenesis 11 cases Gaucher disease type 1 0,94 Fibrodysplasia ossificans progressiva 0,08 Gaucher disease type 2 0,01 Fibrous dysplasia of bone < 0,05 Gaucher disease type 3 0,05 Fibular aplasia - ectrodactyly < 50 cases Geleophysic dwarfism 27 cases Fibular dimelia - diplopodia 11 cases Genetic Parkinson disease 15 Filippi syndrome < 25 cases Genitopatellar syndrome 7 cases Fine-Lubinsky syndrome 5 cases German syndrome 5 cases Floating-Harbor syndrome < 50 cases Geroderma osteodysplastica 30 cases Flynn-Aird syndrome 10 cases Giant axonal neuropathy 20 families Focal dermal hypoplasia 300 cases Giant cell arteritis 8,9 Focal dystonia 11,7 Giant pigmented hairy nevus 2 Focal facial dermal dysplasia < 10 families Gingival fibromatosis - dental 4 cases Focal myositis 50 cases abnormalities

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 13 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Gingival fibromatosis - progressive 2 families GTP cyclohydrolase I deficiency 17 cases deafness Guanidinoacetate methyltransferase 9 cases Gitelman syndrome 2,5 deficiency Glaucoma - ectopia - microspherophakia - 3 cases Guillain-Barré syndrome 3,45 stiff joints - short stature H syndrome 17 cases Glaucoma - sleep apnea 5 cases Haim-Munk syndrome < 100 cases Glioblastoma 11 Hair defect - photosensitivity - 3 cases Global developmental delay - osteopenia 3 cases intellectual deficit - ectodermal defect Hairy cell leukemia 10 Glomerulonephritis - sparse hair - < 10 cases Hallermann-Streiff-François syndrome < 100 cases telangiectasis Harding ataxia 1 Glossopalatine ankylosis 30 cases Hartnup syndrome 4 Glucose-galactose malabsorption 200 cases Hartsfield-Bixler-Demyer syndrome 6 cases Glutaryl-CoA dehydrogenase deficiency 0,4 Heart defects - limb shortening 2 cases Glutathione synthetase deficiency 65 cases Heart-hand syndrome, Slovenian type 10 cases Glycogen storage disease due to LAMP-2 84 cases deficiency HEC syndrome 2 cases Glycogen storage disease type 0 16 cases Helicoid peripapillary chorioretinal 100 cases degeneration Glycogen storage disease type 2 1,1 Hemimelia 4,15 Glycogen storage disease type 4 0,6 Hemolytic anemia due to adenylate 12 cases Glycogen storage disease type 7 < 30 cases kinase deficiency Goldberg-Shprintzen megacolon syndrome 10 cases Hemolytic anemia due to glucophosphate 50 cases Goldenhar syndrome 3,5 isomerase deficiency Goldmann-Favre syndrome < 50 cases Hemolytic anemia due to glutathione 3 cases reductase deficiency Gonadal dysgenesis, XY type - associated 2 cases anomalies Hemolytic anemia due to red cell 5,1 pyruvate kinase deficiency Goodman syndrome 3 cases Hemophilia 7,7 Goodpasture syndrome 0,64 Hemophilia A 6 Gorham-Stout disease 200 cases Hemophilia B 1,3 Gorlin syndrome 1 Hennekam syndrome > 50 cases Gorlin-Chaudhry-Moss syndrome 4 cases Hennekam-Beemer syndrome 2 cases GRACILE syndrome 2,12** Henoch-Schoenlein purpura 8,5 Graft versus host disease 3,4 Hepatic veno-occlusive disease 11 Grange syndrome 6 cases Hepatic veno-occlusive disease - < 25 cases Granulomatous arthritis of childhood 40 families immunodeficiency Granulomatous slack skin < 50 cases Hepatocellular carcinoma 9 Gräsbeck-Imerslund disease 300 cases Hereditary breast and ovarian cancer 25 Gray platelet syndrome 20 cases syndrome Greenberg dysplasia < 10 cases Hereditary chronic pancreatitis 0,125 Greig syndrome 100 cases Hereditary cryohydrocytosis with reduced 2 cases Griscelli disease 60 cases stomatin Growth deficiency - brachydactyly - 2 families Hereditary elliptocytosis 35 dysmorphism Hereditary folate malabsorption 17 cases Growth delay - intellectual deficit - 4 cases Hereditary hyperferritinemia with > 64 cases mandibulofacial dysostosis - microcephaly congenital cataracts - cleft palate Hereditary inclusion body myopathy - 19 cases Growth delay due to insulin-like growth 4 cases joint contractures - ophthalmoplegia factor I deficiency Hereditary neurocutaneous angioma < 10 families Growth retardation - microcephaly - 4 cases digital abnormalities - hypospadias

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 14 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Hereditary neuropathy with liability to 9 Hydrolethalus 5** pressure palsies Hyperandrogenism due to cortisone 11 cases Hereditary orotic aciduria < 20 cases reductase deficiency Hereditary progressive mucinous 13 cases Hypercoagulability syndrome, due to 2 cases histiocytosis glycosylphosphatidylinositol deficiency Hereditary sensory and autonomic 35 cases Hyperekplexia - epilepsy 2 cases neuropathy type 2 Hypereosinophilic syndromes 1,5 Hereditary sensory and autonomic 4 cases Hyperimmunoglobinemia D with recurrent 180 cases neuropathy with deafness and global fever delay Hyperkalemic periodic paralysis 0,75 Hereditary thrombophilia due to 0,2 congenital protein C deficiency Hyperkeratosis - hyperpigmentation 10 cases syndrome Hereditary thrombophilia due to 0,2 congenital protein S deficiency Hyperlipidemia type 3 7,8 Hereditary vascular retinopathy 1 family Hyperlipoproteinemia type 1 0,6 Hereditary vascular retinopathy 1 family Hyperostotic dwarfism, Lenz-Majewski 7 cases type Hermansky-Pudlak syndrome 0,15 Hyperoxaluria 0,2 HERNS syndrome 3 families Hyperplastic polyposis syndrome 50 Heterotaxia 2,5 Hypertrichosis cubiti - short stature 28 cases Hidrotic ectodermal dysplasia, 6 cases Christianson-Fourie type Hypertrichosis lanuginosa congenita < 100 cases Hidrotic ectodermal dysplasia, Halal type 4 cases Hypertrichotic osteochondrodysplasia 18 cases Hirschsprung disease 20 Hypochondroplasia 3,3 Hirschsprung disease - deafness - 2 cases Hypocomplementemic leucocytoclasic < 100 cases polydactyly vasculitis Hirschsprung disease - nail hypoplasia - 3 cases Hypoglossia - hypodactyly < 50 cases dysmorphism Hypogonadotropic hypogonadism - 3 cases Hirschsprung disease - type D 4 cases retinitis pigmentosa brachydactyly Hypohidrotic ectodermal dysplasia - 3 cases Histidinemia 4 hypothyroidism - ciliary dyskinesia Hodgkin lymphoma 10 Hypokalemic periodic paralysis 1 Hodgkin lymphoma, classical 10,5 Hypomagnesemia with normocalciuria 2 cases Holoprosencephaly 7 Hypomandibular faciocranial dysostosis 4 cases Holt-Oram syndrome 1 Hypomyelination - congenital cataract 10 cases Homocarnosinosis 4 cases Hypomyelination - hypogonadotropic 4 cases hypogonadism - hypodontia Homocystinuria due to cystathionine 0,4 beta-synthase deficiency Hypomyelination - hypogonadotropic 4 cases hypogonadism - hypodontia Homocystinuria without methylmalonic 60 cases aciduria Hypomyelination with atrophy of basal 19 cases ganglia and cerebellum Humeroradioulnar synostosis 30 cases Hypoparathyroidism - deafness - renal 12 cases Humerospinal dysostosis 5 cases disease Humeroulnar synostosis 5 cases Hypopituitarism - microphthalmia < 10 cases Huntington disease 6,2 Hypopituitarism - postaxial polydactyly 6 cases Hurler syndrome 1 Hypospadias-hypertelorism-coloboma and 2 cases Hurler-Scheie syndrome 1 deafness Hurler-Scheie syndrome 0,23 Hypotelorism - cleft palate - hypospadias 13 cases Hydrocephalus - blue sclerae - 1 family Hypotonia with lactic acidemia and 3 cases nephropathy hyperammonemia Hydrocephalus - costovertebral dysplasia 8 cases Hypotrichosis - lymphedema - 4 cases - Sprengel anomaly telangiectasia Hydrocephaly - tall stature - joint laxity 2 cases Hypotrichosis simplex 38 cases

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 15 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Hypotrichosis-intellectual deficit, Lopes 2 cases Intellectual deficit - dysmorphism - 4 cases type hypogonadism - diabetes mellitus IBIDS syndrome 15 cases Intellectual deficit - hypoplastic corpus 3 cases callosum - preauricular tag ICF syndrome 50 cases Intellectual deficit - sparse hair - 6 cases Ichthyosis - alopecia - eclabion - 4 cases brachydactyly ectropion - intellectual deficit Intellectual deficit, Birk-Barel type 1 family Ichthyosis - hepatosplenomegaly - 2 cases cerebellar degeneration Intellectual deficit, Kahrizi type 3 cases Ichthyosis - oral and digital anomalies 2 cases Intellectual deficit, X-linked - acromegaly 2 cases - hyperactivity Ichthyosis bullosa of Siemens < 20 cases Intellectual deficit, X-linked - 5 cases Ichthyosis congenita - biliary atresia 2 cases choreoathetosis - abnormal behavior Ichthyosis congenita, harlequin type < 100 cases Intellectual deficit, X-linked - 7 cases Ichthyosis follicularis - atrichia - 10 cases craniofacioskeletal syndrome photophobia Intellectual deficit, X-linked - cubitus 5 cases Ichthyosis prematurity syndrome 16 families valgus - dysmorphism Idiopathic acute eosinophilic pneumonia > 100 cases Intellectual deficit, X-linked - Dandy- 16 cases Idiopathic and/or familial pulmonary 1,5 Walker malformation - basal ganglia arterial hypertension disease - Seizures Idiopathic aplastic anemia 0,4 Intellectual deficit, X-linked - 8 cases dysmorphism - cerebral atrophy Idiopathic hypereosinophilic syndrome 10 Intellectual deficit, X-linked - epilepsy 2 cases Idiopathic hypersomnia 4 - progressive joint contractures - Idiopathic juvenile-onset systemic 6,3 dysmorphism arthritis Intellectual deficit, X-linked - 3 cases Idiopathic pulmonary fibrosis 27 hypogammaglobulinemia - progressive neurological deterioration Idiopathic steroid-sensitive nephrotic 18 syndrome Intellectual deficit, X-linked - 4 cases hypogonadism - ichthyosis - obesity - IMAGe syndrome < 20 cases short stature Iminoglycinuria 6,68 Intellectual deficit, X-linked - hypotonia - 10 cases Immune thrombocytopenic purpura 25 facial dysmorphism - aggressive behavior Immunodeficiency by defective 100 cases Intellectual deficit, X-linked - 12 cases expression of HLA class 2 macrocephaly - macro-orchidism Immunodeficiency due to CD25 deficiency 2 cases Intellectual deficit, X-linked - 2 cases plagiocephaly Immunodeficiency due to interleukin-1 < 15 cases receptor-associated kinase-4 deficiency Intellectual deficit, X-linked - precocious 3 cases puberty - obesity Immunodeficiency due to selective anti- 100 cases polysaccharide antibody deficiency Intellectual deficit, X-linked - psychosis - 6 cases macroorchidism Immunodeficiency with natural-killer cell 4 cases deficiency Intellectual deficit, X-linked - seizures - 4 cases psoriasis Inappropriate antidiuretic hormone 2 cases secretion syndrome Intellectual deficit, X-linked - spastic 9 cases quadriparesis Incontinentia pigmenti 0,2 Intellectual deficit, X-linked, Abidi type 8 cases Infant epilepsy with migrant focal crisis 29 cases Intellectual deficit, X-linked, Armfield 6 cases Infantile choroido cerebral calcification 10 cases type syndrome Intellectual deficit, X-linked, Cantagrel 2 cases Infantile neuroaxonal dystrophy > 150 cases type Infantile onset spinocerebellar ataxia 24 cases Intellectual deficit, X-linked, Chassaing 10 cases Infantile Refsum disease 0,005 type Inflammatory pseudotumor of the liver 143 cases Intellectual deficit, X-linked, Cilliers type 4 cases Intellectual deficit - cataracts - kyphosis 3 cases Intellectual deficit, X-linked, Kroes type 3 cases Intellectual deficit, X-linked, Miles- 4 cases Carpenter type

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number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Intellectual deficit, X-linked, Pai type 1 family Isotretinoin-like syndrome 6 cases Intellectual deficit, X-linked, Reish type 2 cases Isovaleric acidemia 1 Intellectual deficit, X-linked, Schimke 4 cases IVIC syndrome 4 families type Jackson-Weiss syndrome 2 families Intellectual deficit, X-linked, Seemanova 4 cases Jacobsen syndrome 150 cases type Jalili syndrome 29 cases Intellectual deficit, X-linked, Shashi type 9 cases Jeune syndrome 0,2 Intellectual deficit, X-linked, Shrimpton 3 cases type Johanson-Blizzard syndrome 23 cases Intellectual deficit, X-linked, Siderius 4 cases Joubert syndrome 1 type Juberg-Hayward syndrome 10 cases Intellectual deficit, X-linked, Snyder type 11 cases Junctional epidermolysis bullosa 0,06 Intellectual deficit, X-linked, South 16 cases Juvenile chronic recurrent multifocal > 260 cases African type osteomyelitis Intellectual deficit, X-linked, Stevenson 4 cases Juvenile hyaline fibromatosis 50 cases type Juvenile macular degeneration - 7 families Intellectual deficit, X-linked, Stocco Dos 4 cases hypotrichosis Santos type Juvenile myelomonocytic leukemia 0,1 Intellectual deficit, X-linked, Stoll type 4 cases Juvenile neuronal ceroid lipofuscinosis 0,46 Intellectual deficit, X-linked, Van Esch 3 cases type Juvenile Paget's disease 50 cases Intellectual deficit, X-linked, Vitale type 8 cases Juvenile polyposis of infancy 11 cases Intellectual deficit, X-linked, Wei type 5 cases Juvenile psoriatic arthritis 4,2 Intellectual deficit, X-linked, Wilson type 3 cases Juvenile rheumatoid factor-negative 8 polyarthritis Intellectual deficit, X-linked, Wittwer 3 cases type Juvenile rheumatoid factor-positive 4,2 polyarthritis Intellectual deficit, X-linked, Zorick type 6 cases Juvenile temporal arteritis 20 cases Internal carotid agenesis 100 cases Kabuki syndrome 1,16 Interstitial granulomatous dermatitis < 20 cases with arthritis Kaler-Garrity-Stern syndrome 2 cases Intractable diarrhea - choanal atresia - 3 cases Kallmann syndrome 7,7 eye anomalies Kallmann syndrome - heart disease 8 cases Iris coloboma with ptosis - intellectual 10 cases Kaposi's sarcoma 1,7 deficit Kapur-Toriello syndrome 2 cases Iris dysplasia - hypertelorism - deafness 2 cases Kasabach-Merritt syndrome > 175 cases Isolated anophthalmia - microphthalmia 14 KBG syndrome 45 cases Isolated anorectal malformation 24 Kearns-Sayre syndrome 2 Isolated anterior cervical hypertrichosis < 20 cases Kennedy disease 2,8 Isolated brachycephaly 5 Keratoderma - hypotrichosis - leukonychia 2 cases Isolated cloverleaf skull syndrome 150 cases Keratoderma palmoplantar - deafness < 10 families Isolated congenital anosmia < 15 cases Keratoderma palmoplantar - spastic 25 cases Isolated dominant hypomagnesemia 3 families paralysis Isolated ectopia lentis 6,4 Keratosis follicularis - dwarfism - cerebral 6 cases Isolated humeroradial synostosis 150 cases atrophy Isolated Klippel-Feil syndrome 2 Keratosis palmaris et plantaris - < 20 cases clinodactyly Isolated nonketotic hyperglycinemia 0,2 Keratosis palmoplantaris - esophageal < 10 families Isolated Pierre Robin syndrome 8,75 carcinoma Isolated plagiocephaly 10 Keratosis, Nagashima-type 20 cases Isolated scaphocephaly 20 Ketoacidosis due to betaketothiolase 60 cases Isolated trigonocephaly 6,7 deficiency

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 17 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families KID syndrome > 100 cases Leukocyte adhesion deficiency < 350 cases Kimura disease 200 cases Leukocyte adhesion deficiency type II < 10 cases Kozlowski-Brown-Hardwick syndrome 2 cases Leukocyte adhesion deficiency type III 17 cases Krabbe disease 0,75** Leukodystrophy - spastic paraplegia - 9 cases dystonia Kudo-Tamura-Fuse syndrome 2 cases Leukoencephalopathy - ataxia - 8 cases Kumar-Levick syndrome 1 family hypodontia - hypomyelination Lacrimo-auriculo-dento-digital syndrome 20 cases Leukoencephalopathy - dystonia - motor 2 cases Lafora disease < 0,1 neuropathy Lambert-Eaton myasthenic syndrome 1 Leukoencephalopathy - metaphyseal 4 cases Lamellar ichthyosis > 0,33 chondrodysplasia Laminopathy type Decaudain-Vigouroux 9 cases Leukoencephalopathy - palmoplantar 4 cases keratoderma Langerhans cell histiocytosis 2 Leukoencephalopathy with bilateral 29 cases Laron syndrome 0,2 anterior temporal lobe cysts Larsen syndrome 100 cases Leukoencephalopathy with brain stem 39 cases Laryngeal abductor paralysis - intellectual < 20 cases - spinal cord involvement - lactate deficit elevation Laryngo-tracheo-esophageal cleft 1,5 Lewis-Pashayan syndrome 3 cases Late infantile neuronal ceroid 1,3 Lewis-Sumner syndrome 0,9 lipofuscinosis Lhermitte-Duclos disease 220 cases Lateral body wall complex 2** Lichstenstein syndrome 2 cases Lathosterolosis < 5 cases Li-Fraumeni syndrome 400 families LCAT deficiency 30 families Ligneous conjunctivitis 1,1 Leber hereditary optic neuropathy 6,5 Limb-girdle muscular dystrophy 0,8 Legg-Calve-Perthes disease 23 Limb-mammary syndrome 27 cases Leigh syndrome 2,75** Linear atrophoderma of Moulin < 30 cases Lelis syndrome 8 cases Lipoamide dehydrogenase deficiency 20 cases Lemierre syndrome 0,1 Lipodystrophy - intellectual deficit - 3 cases Lennox-Gastaut syndrome 15 deafness LEOPARD syndrome 200 cases Lipodystrophy, familial partial, Köbberling < 20 cases type Leprechaunism 0,1** Lipoid proteinosis > 280 cases Leptospirosis 0,24 Lissencephaly due to TUBA1A mutation < 15 cases Lesch-Nyhan syndrome 0,38 Lissencephaly type 2 0,12 Lethal ataxia with deafness and optic 12 cases atrophy Lissencephaly type III - familial fetal 5 cases akinesia sequence Lethal bone dysplasia, Holmgren type 4 cases Lissencephaly type III - metacarpal bone 2 cases Lethal cystic hygroma - cleft palate 2 cases dysplasia Lethal dermopathy restrictive 30 cases Long chain 3-hydroxyacyl-CoA 1 Lethal faciocardiomelic dysplasia 3 cases dehydrogenase deficiency Lethal hemolytic anemia - genital 2 cases Lopez-Hernandez syndrome 11 cases anomalies Low birth weight - dwarfism - 2 cases Lethal Kniest-like dysplasia 2 cases dysgammaglobulinemia Lethal Larsen-like syndrome < 10 cases Lowe syndrome 0,19 Lethal multiple pterygium syndrome 200 cases Lowry-Wood syndrome < 10 cases Lethal omphalocele-cleft palate syndrome 3 cases Lung fibrosis - immunodeficiency - 2 cases gonadal dysgenesis Lethal osteosclerotic bone dysplasia 8 families Lupus erythematosus, bullous systemic 70 cases Lethal recessive chondrodysplasia 4 cases Lymphangioleiomyomatosis 0,1 Leucinosis 15,6

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number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Lymphedema - atrial septal defects - 3 cases Megacystis microcolon - intestinal 89 cases facial changes hypoperistalsis - hydronephrosis Lymphedema - cerebral arteriovenous 5 cases Megalencephaly - polymicrogyria - post- 6 cases anomaly axial polydactyly - hydrocephalus Macrocephaly - Cutis Marmorata 40 cases MEHMO syndrome 7 cases Telangiectatica Congenita MELAS syndrome 16 Macrocephaly - immune deficiency - 2 cases Melorheostosis 300 cases anemia Mendelian susceptibility to atypical 0,059 Macrocephaly - short stature - paraplegia 2 cases mycobacteria Macrogyria - pseudobulbar palsy 4 cases Meniere disease 42,5 Macrophagic myofasciitis 1 Meningitis, meningococcal 10 Macrostomia - preauricular tags - external 9 cases Menkes disease 0,7 ophthalmoplegia MERRF syndrome 0,9 Madras motor neuron disease 154 cases Mesoaxial synostotic syndactyly with 2 families Maffucci syndrome 250 cases phalangeal reduction Malakoplasia 500 cases Mesomelic dysplasia - skin dimples 2 cases Malaria 3 Mesothelioma 2,7 Malignant atrophic papulosis > 200 cases Metachondromatosis 25 cases Malignant hyperthermia 33 Metachromatic leukodystrophy 0,16 Malignant hyperthermia - arthrogryposis 4 cases Metaphyseal acroscyphodysplasia 4 cases - torticollis Metaphyseal anadysplasia < 20 cases Malonic aciduria 17 cases Metaphyseal chondrodysplasia - retinitis 2 cases Mandibuloacral dysplasia 37 cases pigmentosa Mantle cell lymphoma 3,9 Metaphyseal chondrodysplasia, Jansen 16 cases Marden-Walker syndrome 30 cases type Marfan syndrome 30 Metaphyseal chondrodysplasia, Kaitila 2 cases type Marie Unna congenital hypotrichosis 12 families Metatropic dwarfism 80 cases Marinesco-Sjögren syndrome 200 cases Methimazole embryofetopathy 40 cases Marshall's syndrome with periodic fever 30 cases Methylcobalamin deficiency type cbl E 27 cases Marshall-Smith syndrome 33 cases Methylcobalamin deficiency, cbl G type 33 cases Martinez-Frias syndrome 11 cases Methylmalonic acidemia - homocystinuria 300 cases MASA syndrome 3,5 Methylmalonic aciduria - microcephaly - 2 cases Maternal hyperphenylalaninemia 1,25 cataract Matthew-Wood syndrome 5 cases Methylmalonicacidemia - homocystinuria, 300 cases Mayer-Rokitansky-Küster-Hauser 9 type cbl C syndrome Methylmalonicacidemia - homocystinuria, 5 cases Mazabraud syndrome 54 cases type cbl D McLeod neuroacanthocytosis syndrome 150 cases Methylmalonicacidemia - homocystinuria, 9 cases Meacham syndrome < 15 cases type cbl F Meckel syndrome 4** Mevalonicaciduria 30 cases Meconium aspiration syndrome 2,44 Michels syndrome 7 cases Median cleft lip/mandibule 70 cases Micro syndrome 8 cases Median cleft of the upper lip - corpus > 10 cases Microbrachycephaly - ptosis - cleft lip 2 cases callosum lipoma - cutaneous polyps Microcephalic osteodysplastic dysplasia, 4 cases Medium chain acyl-CoA dehydrogenase 15 Saul-Wilson type deficiency Microcephalic osteodysplastic primordial < 30 cases MEDNIK syndrome 4 families dwarfism types 1 and 3 Medullary thyroid carcinoma 7 Microcephaly - brachydactyly - 3 cases kyphoscoliosis

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 19 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Microcephaly - cardiomyopathy 3 cases Mucolipidosis type 2 0,15** Microcephaly - cleft palate 3 cases Mucolipidosis type 4 > 100 cases Microcephaly - digital anomalies - 2 cases Mucopolysaccharidosis type 1 1,3 intellectual deficit Mucopolysaccharidosis type 2 0,6 Microcephaly - glomerulonephritis - 2 cases Mucopolysaccharidosis type 3 1,1 marfanoid habitus Mucopolysaccharidosis type 4 0,4 Microcephaly - intellectual deficit - 3 cases phalangeal and neurological anomalies Mucopolysaccharidosis type 6 0,16** Microcephaly - micropenis - convulsions 4 cases Mucopolysaccharidosis type 7 < 40 cases Microcephaly - polymicrogyria - corpus 4 cases Mucosulfatidosis 50 cases callosum agenesis Muenke syndrome 1,8** Microcephaly - seizures - intellectual 2 cases Muir-Torre syndrome 205 cases deficit - heart disease MULIBREY nanism 115 cases Microcytic anemia with liver iron overload 3 cases Mullerian derivatives - lymphangiectasia 3 cases Microdontia - type I microtia - deafness 9 cases - polydactyly Microgastria - limb reduction defect 16 cases Multicentric reticulohistiocytosis < 200 cases Microlissencephaly - micromelia 2 cases Multifocal motor neuropathy with 1,5 Microphthalmia - brain atrophy 3 cases conduction block Microscopic polyangiitis 7,5 Multiple endocrine neoplasia type 1 11 Microtia 15 Multiple endocrine neoplasia type 2 3,3 Microtia - eye coloboma - imperforation 1 family Multiple exostoses 2 of the nasolacrimal duct Multiple myeloma 14,25 MIDAS syndrome < 50 cases Multiple sclerosis - ichthyosis - factor 2 cases Midface retraction syndrome, Schinzel- 34 cases VIII deficiency Giedion type Multiple synostoses 20 families Miller-Dieker syndrome 0,3 Multiple system atrophy 4,6 Mitochondrial disease of nuclear origin 9 MURCS association 11,25 Mitochondrial encephalomyopathy , 2 cases Muscular atrophy - ataxia - retinitis 10 cases Ghezzi-Zeviani type pigmentosa - diabetes mellitus Mitochondrial encephalomyopathy 2 cases Muscular dystrophy, Fukuyama type 0,54 aminoacidopathy Myasthenia gravis 20 Mitochondrial myopathy with 7 cases sideroblastic anemia Myelodysplastic syndromes 25 Mitral regurgitation - deafness - skeletal 3 cases Myelofibrosis with myeloid metaplasia 10 anomalies Myhre syndrome 16 cases Mixed dystonia 3 families Myoclonic epilepsy of infancy 106 cases Moebius syndrome 300 cases Myoclonus - cerebellar ataxia - deafness 4 cases Mohr-Tranebjaerg syndrome 46 cases Myoclonus hereditary - progressive distal < 10 cases Monoclonal Ig light chain-associated 100 cases muscular atrophy Fanconi syndrome Myoneurogastrointestinal encephalopathy 87 cases Mononen-Karnes-Senac syndrome 5 cases syndrome Monosomy 18p < 200 cases Myopathy due to calsequestrin and 4 cases SERCA1 protein overload Monosomy 22q11 20 N syndrome 3 cases Monosomy 22q13 > 200 cases Naegeli-Franceschetti-Jadassohn 0,035 Monosomy 5p 4,6 syndrome Monosomy 9q22.3 2 cases Nail patella-like - renal disease 3 cases Moore-Federman syndrome 6 cases Nail-patella syndrome 2 Mosaic variegated aneuploidy syndrome 29 cases Nance-Horan syndrome 50 families Mowat-Wilson syndrome < 200 cases Nanism due to growth hormone 3 cases Moyamoya disease 3,16 qualitative anomaly

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number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Narcolepsy-cataplexy 26 Nijmegen breakage syndrome 1** NARP/MILS syndrome 8,5 Nodular regenerative hyperplasia of the 3 liver Nasopalpebral lipoma - coloboma - < 30 cases telecanthus Non-distal trisomy 10p 60 cases Nemaline myopathy 1 Non-distal trisomy 12p 2** Neonatal diabetes - congenital 2 cases Non-distal trisomy 8q > 30 cases hypothyroidism - congenital glaucoma - Non-Hodgkin lymphoma 36 hepatic fibrosis - polycystic kidneys Nonspherocytic hemolytic anemia due to 17 families Neonatal diabetes mellitus 0,2 hexokinase deficiency Neonatal hemochromatosis 100 cases Noonan syndrome 50 Neonatal hypoxic and ischemic brain 10 Norrie disease 300 cases injury North Carolina macular dystrophy 2 families Neonatal hypoxic and ischemic brain 9 injury Not NOTCH3-related small vessel disease 2 cases of the brain Neonatal ichthyosis - sclerosing < 10 cases cholangitis Obesity - colitis - hypothyroidism - 2 cases cardiac hypertrophy - developmental Neovascular glaucoma 24,4 delay Nephroblastoma 10,1 Obesity due to congenital leptin < 30 cases Nephrogenic diabetes insipidus 0,5 deficiency Nephronophtisis familial, adult form - 2 cases Obesity due to melanocortin-4 receptor 50 spastic quadriparesia deficiency Nephropathy - deafness - 5 cases Obesity due to prohormone convertase-I 2 cases hyperparathyroidism deficiency Nephrosis - deafness - urinary tract - 5 cases Obesity due to pro-opiomelanocortin 7 cases digital malformations deficiency Netherton disease 1,35 Ochoa syndrome > 100 cases Neu-Laxova syndrome 60 cases Ocular coloboma 1 Neuroaxonal dystrophy - renal tubular 3 cases Ocular motor apraxia, Cogan type 50 cases acidosis Oculocerebrocutaneous syndrome 36 cases Neurocutaneous syndrome, Bicknell type 4 cases Oculocerebrofacial syndrome, Kaufman 9 cases Neurodegeneration due to 4 cases type 3-hydroxyisobutyryl-CoA hydrolase Oculocutaneous albinism 7,15 deficiency Oculodental syndrome, Rutherfurd type 1 family Neurodegeneration due to 2 cases 3-hydroxyisobutyryl-CoA hydrolase Oculodentodigital dysplasia 243 cases deficiency Oculo-digito-esophageal-duodenal < 50 cases Neuroectodermal syndrome, Johnson type < 30 cases syndrome Neuroectodermal-endocrine syndrome 4 cases Oculogastrointestinal muscular dystrophy 1 family Neurofibromatosis type 1 25 Oculoosteocutaneous syndrome 3 cases Neurofibromatosis type 2 0,5 Oculo-oto-facial dysplasia 4 cases Neurometabolic disorder due to serine < 30 cases Oculo-palato-cerebral syndrome 5 cases deficiency Oculopharyngeal muscular dystrophy 1 Neuromyelitis optica 1,5 Oculotrichodysplasia 2 cases Neuropathy with hearing impairment 1 family Odontoleukodystrophy 4 cases Neutropenia cyclic 0,1 Odontomicronychial dysplasia 5 cases Nevo syndrome 10 cases Odonto-onycho-dermal dysplasia < 15 cases Niemann-Pick disease 2,5** Odontotrichomelic syndrome 4 cases Niemann-Pick disease type A 0,25** Odonto-tricho-ungual-digito-palmar 21 cases Niemann-Pick disease type B 0,4** syndrome Niemann-Pick disease type B 0,4 Okamoto syndrome 2 cases Niemann-Pick disease type C 0,85 Oligoarticular juvenile arthritis 20,5

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 21 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Oligocone trichromacy 14 cases Palmoplantar keratoderma - amyotrophy 4 cases Olmsted syndrome 32 cases Palmoplantar keratoderma - XX sex 5 cases reversal - predisposition to squamous cell Omodysplasia 30 cases carcinoma Omphalocele 12 Palmoplantar porokeratosis of Mantoux < 10 cases Ondine syndrome 2,25 Pancreatic hypoplasia - diabetes - heart < 10 cases Onycho-tricho-dysplasia - neutropenia 5 cases disease Ophthalmo acromelic syndrome 30 cases Pancreatoblastoma 60 cases Opitz BBB/G syndrome 3 Papillon-Lefevre syndrome 0,25 Opsismodysplasia 25 cases Paraneoplastic pemphigus > 60 cases Optic atrophy 6 Paraplegia - brachydactyly - cone-shaped 5 cases Oral-facial-digital syndrome type 1 1,2 epiphysis Oral-facial-digital syndrome type 3 3 cases Paraplegia - intellectual deficit - 4 cases hyperkeratosis Oral-facial-digital syndrome type 4 16 cases PARC syndrome 2 cases Oral-facial-digital syndrome type 5 4 cases Parietal foramina 5 Oral-facial-digital syndrome type 6 29 cases Paroxysmal extreme pain disorder 4 families Oral-facial-digital syndrome type 8 2 families Paroxysmal hemicrania 2 Orbital leiomyoma 16 cases Paroxysmal nocturnal hemoglobinuria 0,55 Ornithine carbamoyltransferase deficiency 1 Parsonage-Turner syndrome 3,3 Ossification anomalies - psychomotor 2 cases development delay Partial acquired lipodystrophy 250 cases Osteochondritis dissecans 35 Partial atrioventricular canal 20 Osteochondrodysplatic nanism - deafness 2 cases Partial chromosome Y deletion 42 - retinitis pigmentosa Partial pancreas agenesis 8 cases Osteocraniostenosis 12 cases Partington syndrome 2 families Osteodysplasty, Melnick-Needles type > 50 cases Patent arterial duct 50 Osteogenesis imperfecta 6,5 Pearson syndrome 60 cases Osteogenesis imperfecta - retinopathy - 2 cases Pelizaeus-Merzbacher disease 0,25 seizures - intellectual deficit PELVIS syndrome 11 cases Osteopathia striata - cranial sclerosis 100 cases Pelviscapular dysplasia 4 cases Osteopetrosis with renal tubular acidosis 50 cases Pemphigus vulgaris 3,8 Osteopoikilosis - short stature - 4 cases Pendred syndrome 5,5 intellectual deficit Pericarditis - arthropathy - camptodactyly < 30 families Osteoporosis - pseudoglioma 0,05 Perinatal-lethal Gaucher disease 0,01 Osteoporosis-oculocutaneous- 3 cases hypopigmentation syndrome Perioral myoclonia with absences < 10 cases Osteosarcoma 5 Peripheral neuropathy, Fiskerstrand type 3 cases Osteosclerosis - ichthyosis - premature 3 cases Perlman syndrome 30 cases ovarian failure Permanent neonatal diabetes mellitus - 4 cases Otodental syndrome 9 families pancreatic and cerebellar agenesis Otopalatodigital syndrome 30 cases Perrault syndrome 34 cases Otospondylomegaepiphyseal dysplasia < 30 cases Persistent hyperinsulinemic hypoglycemia 2 of infancy Overhydrated hereditary stomatocytosis 20 families Peters-plus syndrome 50 cases Ovotesticular disorder of sex development > 500 cases Peutz-Jeghers syndrome 2,2 P2Y12 deficiency 5 cases Pfeiffer syndrome 1 Pachydermoperiostosis 204 cases PHACE syndrome 100 cases Pachyonychia congenita 230 cases Phenylketonuria 4 Pacman dysplasia < 10 cases Pheochromocytoma and secreting 10 Pallister-Hall syndrome 100 cases paraganglioma

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 22 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Phosphoenolpyruvate carboxykinase < 10 cases Primary pulmonary hemosiderosis 250 cases deficiency Primary sclerosing cholangitis 11 Phosphoglycerate kinase 1 deficiency 23 cases Progeria 0,25** Phosphoribosylpyrophosphate synthetase < 30 families Progeria - short stature - pigmented nevi < 10 cases superactivity Progressive bifocal chorioretinal atrophy 2 families Phytosterolemia 40 cases Progressive bulbar paralysis of childhood < 40 cases PIBIDS syndrome 20 cases Progressive cavitating 19 cases Piebaldism 0,25 leukoencephalopathy Pierre Robin syndrome - faciodigital 2 cases Progressive neurodegeneration - joint 2 cases anomaly laxity - cataract Pierson syndrome 22 cases Progressive supranuclear palsy 3,7 Pili torti - onychodysplasia 1 family Prolidase deficiency 50 cases Pilodental dysplasia - refractive errors 2 cases Propionic acidemia 3,75 Pitt-Hopkins syndrome 150 cases Proteus syndrome 200 cases Pityriasis rubra pilaris 48 cases Proximal myotonic myopathy 1 Plummer-Vinson syndrome 25 cases Proximal spinal muscular atrophy 3 Poikiloderma of Kindler 100 cases Proximal spinal muscular atrophy type 1 1,25 Poland syndrome 2 Proximal spinal muscular atrophy type 2 1,42 Pollitt syndrome 10 cases Proximal spinal muscular atrophy type 3 0,26 Polyarteritis nodosa 3,07 Proximal spinal muscular atrophy type 4 0,32 Polycystic lipomembranous osteodysplasia 0,15 Pseudoachondroplasia 1,6 - sclerosing leukoencephalopathy Pseudodiastrophic dysplasia 10 cases Polycystic ovaries - urethral sphincter 33 cases dysfunction Pseudohypoaldosteronism type 1 70 cases Polycythemia vera 25 Pseudoprogeria syndrome 2 cases Polymyositis 14,8 Pseudoxanthoma elasticum 2,5 Polysyndactyly - cardiac malformation 6 cases Pseudo-Zellweger syndrome < 10 cases Pontocerebellar hypoplasia type 1 6 families Psychomotor retardation due to 3 cases S-adenosylhomocysteine hydrolase Pontocerebellar hypoplasia type 2 < 30 cases deficiency Pontocerebellar hypoplasia type 4 3 cases Pterygium colli - intellectual deficit - 2 cases Pontocerebellar hypoplasia type 5 3 cases digital anomalies Pontocerebellar hypoplasia type 6 3 cases Ptosis - strabismus - ectopic pupils 1 family Porokeratotic eccrine ostial and dermal 25 cases Ptosis - strabismus - rectus abdominis 2 cases duct nevus diastasis Postaxial acrofacial dysostosis < 30 cases Pulmonary alveolar proteinosis 0,1 Posterior column ataxia - retinitis 13 cases Pure autonomic failure 1 pigmentosa Pyknoachondrogenesis 5 cases Posterior fusion of lumbosacral vertebrae 3 cases Pyle disease < 30 cases - blepharoptosis Pyogenic arthritis - pyoderma 34 cases Post-transplant lymphoproliferative 26,2 gangrenosum - acne disease Pyridoxin-dependent epilepsy 0,15 Potocki-Shaffer syndrome 23 cases Qazi-Markouizos syndrome 3 cases Prader-Willi syndrome 10,7 Radiation proctitis 35 Preaxial polydactyly 25 Radio-ulnar synostosis - amegakaryocytic < 20 cases Primary achalasia 10 thrombocytopenia Primary biliary cirrhosis 13,5 Rambaud-Galian syndrome 3 cases Primary ciliary dyskinesia 5 RAPADILINO syndrome < 20 cases Primary erythermalgia 30 families Rapid-onset dystonia-parkinsonism 3 families Primary lateral sclerosis 1,5 Rapp-Hodgkin syndrome 72 cases

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 23 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Rasmussen subacute encephalitis > 100 cases Sanfilippo syndrome type A 0,3 Recessive hereditary methemoglobinemia < 100 cases Sarcoidosis 15 type 2 Sarcosinemia 2 Recurrent infections - short stature - 4 cases Say-Barber-Miller syndrome 2 cases hypopigmentation - coarse face Scalp defects - postaxial polydactyly 2 cases Reducing body myopathy 4 families Scalp-ear-nipple syndrome 30 cases Refsum disease 0,1 SCARF syndrome 2 cases Regional odontodysplasia 139 cases Scheie syndrome 0,2 Relapsing polychondritis 0,35 Scheie syndrome 0,2 Renal-hepatic-pancreatic dysplasia - 10 cases Dandy-Walker cysts Schimke immuno-osseous dysplasia 50 cases Rendu-Osler-Weber disease 3,5 Schinzel syndrome < 10 families Renpenning syndrome 10 families Schizencephaly 1,54 Resistance to thyrotropin-releasing 2 cases Schizophrenia - intellectual deficit - 1 family hormone syndrome deafness - retinitis Retinal arteries tortuosity 100 cases Schnitzler syndrome 50 cases Retinal degeneration - nanophthalmos - 7 cases Schopf-Schulz-Passarge syndrome 19 cases glaucoma Schwartz-Jampel syndrome 100 cases Retinitis pigmentosa 27,5 Scleroderma 42 Retinitis pigmentosa - intellectual deficit 2 families Sea-blue histiocytosis 60 cases - deafness - hypogenitalism Sebastian syndrome < 10 families Retinoblastoma 5,4 Seborrhea-like dermatitis with 44 cases Retinohepatoendocrinologic syndrome 7 cases psoriasiform elements Rett syndrome 4,15 Seckel syndrome 100 cases Rhabdoid tumor 500 cases Secondary amyloidosis 17 Rheumatic fever 5 Segmental odontomaxillary dysplasia 32 cases Rhombencephalosynapsis 50 cases Seizures - intellectual deficit due to 3 cases Rickettsialpox > 800 cases hydroxylysinuria Rieger syndrome 0,5 Senior-Loken syndrome 0,1 Ring chromosome 1 34 cases Sensenbrenner syndrome 15 cases Ring chromosome 10 < 20 cases Sensorineural hearing loss - early greying 3 cases - essential tremor Ring chromosome 14 50 cases SERKAL syndrome 3 cases Ring chromosome 17 14 cases Serpentine fibula - polycystic kidneys 6 cases Ring chromosome 18 70 cases Severe achondroplasia - developmental 4 cases Ring chromosome 20 > 50 cases delay - acanthosis nigricans Ring dermoid of cornea < 30 cases Severe combined immunodeficiency due 0,22 Roberts syndrome/SC phocomelia < 150 cases to adenosine deaminase deficiency Robinow syndrome > 120 cases Severe congenital neutropenia 0,4 Robinow-like syndrome 2 cases Severe intellectual deficit - epilepsy 2 cases - anal anomalies - distal phalangeal Rolled and spiral hairs - palmoplantar 4 cases hypoplasia keratoderma Severe X-linked intellectual deficit, 7 cases Rothmund-Thomson syndrome 300 cases Gustavson type Rubella panencephalitis > 20 cases Sezary's syndrome 0,18 Rubinstein-Taybi syndrome 1 Short bowel syndrome 3,4 Rudiger syndrome 2 cases Short fifth metacarpals - insulin 1 family Saethre-Chotzen syndrome 3 resistance Sakati-Nyhan syndrome < 5 cases Short stature - intellectual deficit - eye 3 cases Sandhoff disease 0,75 anomalies - cleft lip/palate

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number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Short stature - pituitary and cerebellar 1 family Spondyloepimetaphyseal dysplasia - 2 cases defects - small sella turcica abnormal dentition Short stature - webbed neck - heart 4 cases Spondyloepimetaphyseal dysplasia - 5 cases disease hypotrichosis Short stature, Brussels type 2 cases Spondyloepimetaphyseal dysplasia, 3 cases aggrecan type SHORT syndrome 30 cases Spondyloepimetaphyseal dysplasia, 3 cases Shprintzen-Goldberg syndrome < 50 cases Bieganski type Shwachman-Diamond syndrome 200 cases Spondyloepimetaphyseal dysplasia, 2 cases Sialidosis type 1 0,02** Genevieve type Sialidosis type 2 0,02** Spondyloepiphyseal dysplasia tarda, Kohn 3 cases Sick sinus syndrome 11 cases type Sickle cell anemia 11 Spondyloepiphyseal dysplasia, Byers type 4 cases Siegler-Brewer-Carey syndrome 2 cases Spondyloepiphyseal dysplasia, Cantu type 4 cases Silent sinus syndrome 98 cases Spondyloepiphyseal dysplasia, MacDermot 4 cases type Sillence syndrome 5 cases Spondyloepiphyseal dysplasia, Nishimura 4 cases Silver-Russell syndrome 400 cases type Simpson-Golabi-Behmel syndrome > 100 cases Spondyloepiphyseal dysplasia, Reardon 1 family Simpson-Golabi-Behmel syndrome type 2 4 cases type Singleton-Merten dysplasia < 10 cases Spondylometaphyseal dysplasia 1 Sinus histiocytosis with massive 500 cases Spondylometaphyseal dysplasia - bowed 2 cases lymphadenopathy forearms - facial dysmorphism Sirenomelia 1** Spondylometaphyseal dysplasia - cone- 8 cases rod dystrophy Sjögren-Larsson syndrome 0,4 Spondylometaphyseal dysplasia with 4 cases Skeletal dysplasia - intellectual deficit 2 families combined immunodeficiency Small cell lung cancer 10 Spondylometaphyseal dysplasia, A4 type 2 cases Smith-Lemli-Opitz syndrome 3,3 Spondylometaphyseal dysplasia, Golden 3 cases Smith-Magenis syndrome 4 type Soft tissue sarcomas 13 Spontaneous periodic hypothermia < 30 cases Solar urticaria 3,6 Sporadic inclusion body myositis 0,49 Sotos syndrome 7** Sporotrichosis 55 cases Sparse hair - short stature - skin 4 cases Squamous cell carcinoma of head and 46 anomalies neck Spastic paraplegia - glaucoma - 2 families Stapes ankylosis with broad thumbs and 6 families intellectual deficit toes Spastic paraplegia - nephritis - deafness 4 cases Stargardt disease 11,25 Spastic paraplegia - precocious puberty 2 cases Steinert myotonic dystrophy 4,5 Spastic quadriplegia - retinitis 2 cases Sternal cleft < 2 pigmentosa - intellectual deficit Stern-Lubinsky-Durrie syndrome 7 cases Spasticity - intellectual deficit - X-linked 6 cases Steroid dehydrogenase deficiency - dental 1 family epilepsy anomalies Spherocytosis hereditary 20 Stickler syndrome 13,5 Spina bifida 50 Stiff-man syndrome 0,1 Spinal muscular atrophy - Dandy-Walker 2 cases Stimmler syndrome 2 cases complex - cataracts Stoll-Alembik-Finck syndrome 2 cases Split hand - split foot 1,1 Stormorken-Sjaastad-Langslet syndrome 6 cases Split hand - split foot - deafness 22 cases Stromal keratitis 16 Split hand - urinary anomalies - spina 3 cases bifida Stromal keratitis 16 Spondyloenchondrodysplasia 36 cases Suarez-Stickler syndrome 3 cases

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 25 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Subcorneal pustular dermatosis 200 cases Thrombotic thrombocytopenic purpura 24,6 Succinic acidemia 50 cases Thumb absent - short stature - immune 3 cases deficiency Succinyl-CoA acetoacetate transferase 10 cases deficiency Thumb stiffness - brachydactyly - 6 cases intellectual deficit Sudden infant death - dysgenesis of the 21 cases testes Thymic-renal-anal-lung dysplasia 3 cases Summitt syndrome 3 cases Thyrocerebrorenal syndrome 2 cases Superficial pemphigus 1,2 Thyrotoxic periodic paralysis 139 cases Supravalvar aortic stenosis 12,5 Tibial aplasia - ectrodactyly 0,1 Susac syndrome < 100 cases Tibial hemimelia 0,1 Symmetrical thalamic calcifications 29 cases Tibial muscular dystrophy 6 Symphalangism with multiple anomalies 6 cases Tietz syndrome 1 family of hands and feet Tomé-Brunet-Fardeau syndrome 4 cases Syndactyly - telecanthus - anogenital and 6 cases Torg-Winchester syndrome 12 cases renal malformations Toriello-Carey syndrome 60 cases Syndactyly type 1 25 Toriello-Lacassie-Droste syndrome 10 cases Syndactyly type 4 4 cases Torticollis - keloids - cryptorchidism - 7 cases Syndactyly, Cenani-Lenz type < 30 cases renal dysplasia Syndromic progressive non-infectious 10 cases Townes-Brocks syndrome 0,42 anterior vertebral fusion Tracheal agenesis 1** Syndromic X-linked intellectual deficit 7 10 cases Tracheobronchomegaly < 100 cases Syndromic X-linked intellectual deficit < 10 families due to JARID1C mutation Transmissible spongiform 0,3 encephalopathies Syngnathia multiple anomalies 2 cases Treacher-Collins syndrome 6 Synspondylism 24 cases Treft-Sanborn-Carey syndrome 23 cases Syringomyelia 8,4 Trichodental syndrome < 5 families Systemic mastocytosis 3,3 Tricho-dento-osseous syndrome > 30 cases Systemic sclerosis 16,2 Trichodysplasia - amelogenesis imperfecta 1 family Takayasu arteritis 0,45 Trichomegaly - cataract - hereditary 2 cases Talo-patello-scaphoid osteolysis 2 cases spherocytosis Tangier disease > 70 cases Trichomegaly - retina pigmentary 11 cases Taurodontia - absent teeth - sparse hair < 15 cases degeneration - dwarfism Tay-Sachs disease 0,3** Tricho-odonto-onychial dysplasia 4 cases T-cell and NK-cell tumor 30 Tricho-retino-dento-digital syndrome 9 cases Teebi-Shaltout syndrome 2 cases Trichorhinophalangeal syndrome type 1 > 100 cases and 3 Temtamy syndrome 3 cases Tricuspid atresia 5 Terminal osseous dysplasia - pigmentary 18 cases defects Trigonocephaly - bifid nose - acral 2 cases anomalies Tetralogy of Fallot 45 Trigonocephaly - broad thumbs 2 cases Thalidomide embryopathy 5000 cases Trigonocephaly - short stature - 3 cases Thanatophoric dwarfism 3,5** developmental delay Thiamine-responsive megaloblastic 30 families Triose phosphate-isomerase deficiency 30 cases anemia with diabetes mellitus and sensorineural deafness Triphalangeal thumbs - 4 families brachyectrodactyly Thickened earlobes - conductive deafness 2 families Triple A syndrome 100 cases Thomsen and Becker disease 5 Triple H syndrome 50 cases Thoracolaryngopelvic dysplasia < 10 cases Triplo-X syndrome 42,5 Thrombocytopenia - Robin sequence 2 cases Trisomy 13 13**

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 26 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of number of Estimated Estimated published published Diseases name prevalence Diseases name prevalence cases or cases or (/100,000) (/100,000) families families Trisomy 18 9** Whipple disease 1000 cases Trisomy 21 50 Wieacker-Wolff syndrome 6 cases Tritanopia 4,8 Wiedemann-Rautenstrauch syndrome 25 cases Tuberculosis 20 Williams syndrome 13,3 Tuberous sclerosis 8,8 Wilson disease 5,84 Tubular renal disease - cardiomyopathy 2 cases Wilson-Turner syndrome > 14 cases Tufted angioma > 200 cases Wiskott-Aldrich syndrome 0,15 Turner syndrome 20 Wolcott-Rallison syndrome < 60 cases Tyrosinemia type 1 0,05 Wolf-Hirschhorn syndrome 2** Tyrosinemia type 2 < 100 cases Wolfram syndrome 0,57 Uhl anomaly 84 cases Wolman disease 0,28** Ulbright-Hodes syndrome 3 cases Woolly hair - hypotrichosis - everted 1 family lower lip - outstanding ears Ulnar/fibula ray defect - brachydactyly 1 family Woolly hair - palmoplantar keratoderma - < 20 cases Umbilical cord ulceration - intestinal 15 cases dilated cardiomyopathy atresia Worster-Drought syndrome 3,7 Unilateral adactylia 34 Wrinkly skin syndrome < 30 cases Unverricht-Lundborg disease 0,2 Xanthinuria 150 cases Upington disease 1 family Xanthomatosis cerebrotendinous 0,13 Usher syndrome 3,5 Xeroderma - talipes - enamel defects 2 cases VACTERL with hydrocephalus < 10 families Xeroderma pigmentosum 0,5 Van den Bosch syndrome 1 family XK aprosencephaly < 10 cases Van Der Woude syndrome 2 X-linked adrenoleukodystrophy 5 Vasculitis 6,3 X-linked agammaglobulinemia 0,45 VATER association 23 X-linked Charcot-Marie-Tooth disease 1,6 Vernal keratoconjunctivitis 21 X-linked creatine transporter deficiency 17 cases Vici syndrome 8 cases X-linked diffuse leiomyomatosis - Alport 0,1 Visceral neuropathy - brain anomalies - 2 cases syndrome facial dysmorphism - developmental delay X-linked dominant chondrodysplasia 0,5 Vitamin B12 responsive methylmalonic 60 cases punctata acidemia type cbl A X-linked hereditary sensory and 1 family Von Hippel-Lindau disease 1,9 autonomic neuropathy with deafness Von Willebrand disease 12,5 X-linked ichthyosis 16,6 Vulvovaginal gingival syndrome 127 cases X-linked immune dysregulation - 7 families W syndrome 6 cases polyendocrinopathy - enteropathy Waardenburg syndrome 2,4 X-linked immunoneurologic disorder 5 cases Waardenburg-Shah syndrome 50 cases X-linked intellectual deficit - ataxia - 9 cases Waldenström macroglobulinemia 2,6 apraxia Walker-Warburg syndrome 1,65** X-linked intellectual deficit, Najm type 5 cases Weaver syndrome 30 cases X-linked lymphoproliferative disease 0,1 Weaver-Williams syndrome 2 cases X-linked mandibulofacial dysostosis 7 cases Wegener granulomatosis 6,6 X-linked myopathy with excessive 15 families autophagy Weill-Marchesani syndrome 128 cases X-linked neurodegenerative syndrome, 7 cases Wells syndrome 80 cases Bertini type Werner syndrome 0,45 X-linked neurodegenerative syndrome, 10 cases West syndrome 3,7** Hamel type Western equine encephalitis > 600 cases X-linked recessive corpus callosum 11 cases dysgenesis WHIM syndrome 40 cases

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 27 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

number of Estimated published Diseases name prevalence cases or (/100,000) families X-linked recessive intellectual deficit - 1 family macrocephaly - ciliary dysfunction X-linked recessive ocular albinism 2 X-linked retinoschisis 4,5 X-linked severe congenital neutropenia 7 cases X-linked sideroblastic anemia < 200 cases X-linked sideroblastic anemia - ataxia 5 families X-linked spastic paraplegia type 16 1 family X-linked spastic paraplegia type 2 < 100 cases X-linked spastic paraplegia type 34 24 cases X-linked spinocerebellar ataxia type 3 5 cases Young adult-onset Parkinsonism 37,5 Young-Simpson syndrome 5 cases Zellweger syndrome 1,1 Zellweger-like syndrome without 2 cases peroxisomal anomalies Zollinger-Ellison syndrome 5,3 Zunich-Kaye syndrome 6 cases

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Editor-in-chief: Ségolène Aymé  Editor of the report : Annie Olry  Visual design : Céline Angin

The correct form when quoting this document is : « Prevalence of rare diseases: Bibliographic data », Orphanet Report Series, Rare Diseases collection, May 2010, Number 1 : Listed in alphabetical order of diseases, http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf

** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2010 - Number 1 28 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf