Orphanet Rep Rt Series Rare Diseases Collection

Orphanet Rep rt Series Rare Diseases collection

Prevalence of rare diseases : Bibliographic data

Listed in alphabetical order of diseases

www.orpha.net November 2008 Number 1 Method

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

For any questions or comments, please contact us: [email protected] Orphanet Report Series - Prevalence of rare diseases: Bibliographic data November 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Number 1 Prevalence or reported number of published cases listed in alphabetical order of diseases

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families 2,8 dihydroxyadenine urolithiasis 1.7 Acrofacial dysostosis, palagonia type 4 cases 3C syndrome 25 cases Acrofacial dysostosis, postaxial < 30 cases 3-hydroxy 3-methylglutaryl-CoA 6 cases Acrofacial dysostosis, Preis type 1 case (HMG) synthase Acrofacial dysostosis, Rodriguez type < 10 cases 3-hydroxyacyl-CoA dehydrogenase, 1 Acro-fronto-facio-nasal dysostosis 5 cases long chain, deficiency of Acromegaloid facial appearance < 20 cases 3M syndrome 40 cases syndrome 3-methylcrotonylglycinuria 2.25 Acromegaloid facies - hypertrichosis < 20 cases 3-methylglutaconic aciduria, type 1 20 cases Acromegaly 5 3-methylglutaconic aciduria, type 3 10 Acromegaly - cutis verticis gyrata - 16 cases 4-hydroxybutyricaciduria 350 cases corneal leukoma 5-oxoprolinase deficiency 8 cases Acromelanosis < 10 cases 6-pyruvoyl-tetrahydropterin 248 cases Acromesomelic dysplasia brahimi 3 cases synthase, deficiency bacha type 6q terminal deletion 19 cases Acromesomelic dysplasia, Hunter- 10 cases Thomson type Aarskog-Scott syndrome > 200 cases Acromesomelic dysplasia, Maroteaux 50 cases Aase-Smith syndrome < 10 cases type Ablepharon macrostomia syndrome 15 cases Acromicric dysplasia < 40 cases Abruzzo-Erickson syndrome 4 cases Acroosteolysis dominant type 50 cases Acalvaria < 1** Acro-pectoral syndrome 22 cases Acanthamoeba keratitis 1 Acro-pectoro-renal field defect 12 cases Acatalasemia 3.1 Acropectorovertebral dysplasia < 30 cases Aceruloplasminemia 0.05 Acrorenal syndrome 20 cases Achalasia - microcephaly 5 cases Acro-renal-mandibular syndrome 7 cases Achalasia, primary 10 Acro-renal-ocular syndrome < 20 families Acheiropodia < 10 families Acute interstitial pneumonia 3.8 Achondrogenesis > 100 cases Acute Respiratory Distress Syndrome, 30 Achondroplasia 4.5 adult Achromatopsia 3.33 Acyl-CoA dehydrogenase, medium 15 Ackerman syndrome 8 cases chain, deficiency of Aconitase deficiency 19 cases Adactylia unilateral 34 Acrocallosal syndrome, Schinzel type 34 cases Adamantinoma 513 cases Acrocephalosyndactyly 4.6 Adducted thumbs - arthrogryposis, 3 families Christian type Acrocraniofacial dysostosis 2 cases Adducted thumbs-arthrogryposis, 5 cases Acrodermatitis enteropathica, zinc 0.2 Dundar type deficiency type Adenosine monophosphate 200 cases Acrofacial dysostosis postaxial, 1 case deaminase deficiency atypical Adenylosuccinate lyase deficiency 50 cases Acrofacial dysostosis, autosomal 2 cases recessive Adrenal hyperplasia, congenital 10 Acrofacial dysostosis, Catania type 6 cases Adrenocortical carcinoma 1 Acrofacial dysostosis, Nager type 90 cases Adrenoleukodystrophy, X-linked 5

** Prevalence at birth November 2008 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data Number 1 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

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families ADULT syndrome 14 cases Amniotic bands 4** Agammaglobulinemia - 3 cases Amoebiasis due to free-living 1.75 microcephaly - craniosynostosis - amoebae severe dermatitis Amyotrophic lateral sclerosis 6 Agammaglobulinemia X-linked 0.45 Anaemia, sideroblastic, X-linked - 5 families Agenesis of the corpus callosum - 2 cases ataxia mental retardation - coloboma - Androgen insensitivity syndrome 13 micrognathia ANE syndrome 5 cases Agnathia holoprosencephaly situs 30 cases inversus Anencephaly 3.2** Agonadism - dextrocardia - 6 cases Angelman syndrome 6.5 diaphragmatic hernia Angel-shaped phalango-epiphyseal 15 cases Aicardi syndrome 200 cases dysplasia Aicardi-Goutieres syndrome 120 cases Angioma neurocutaneous, hereditary < 10 families Alagille syndrome 1.4 Angio-osteohypertrophic syndrome 1000 cases Alar cartilages hypoplasia - 2 cases Aniridia 1.75 coloboma - telecanthus Aniridia - absent patella 3 cases Albers-Schonberg osteopetrosis 1 Aniridia - cerebellar ataxia - mental > 10 families Albinism ocular - late onset 7 cases deficiency sensorineural deafness Aniridia - ptosis - mental 3 cases Albinism-deafness syndrome 1 family retardation - obesity, familial form Albright hereditary osteodystrophy 0.72 Aniridia - renal agenesis - 2 cases psychomotor retardation Alexander disease 300 cases Aniridia-mental retardation syndrome 2 cases Al-Gazali-Dattani syndrome 3 cases Anisakiasis 3.8 Alkaptonuria 0.3 Ankyloblepharon - ectodermal 8 families Alopecia - congenita keratosis 1 family defects - cleft lip palate palmoplantaris Ankyloblepharon filiforme - 2 families Alopecia - contractures - dwarfism - 5 cases imperforate anus mental retardation Ankylosing vertebral hyperostosis 8 cases Alopecia - hypogonadism - 2 cases with tylosis extrapyramidal disorder Anonychia - onychodystrophy with 11 cases Alopecia- epilepsy - pyorrhea - 12 cases hypoplasia or absence of distal mental subnormality phalanges Alopecia totalis 10.5 Anonychia microcephaly 5 cases Alpers syndrome 0.025 Anonychia with flexural 3 cases Alpha thalassemia - mental 168 cases pigmentation retrdation, X-linked Anophthalmia - hypothalamo- 30 cases Alpha-1 antitrypsin deficiency 25 pituitary insufficiency Alpha-mannosidosis 0.1 Anophthalmia - megalocornea - 3 cases Alpha-sarcoglycanopathy 0.57 cardiopathy - skeletal anomalies Alport syndrome 2 Anophthalmia - Microphthalmia, 14 isolated Alström syndrome 300 cases Alveolar echinococcosis < 1000 cases Anophthalmia plus syndrome 4 cases Alzheimer disease, familial 5.3 Anophthalmia/microphthalmia - 14 cases esophageal atresia Amaurosis - hypertrichosis 2 cases Anorchidia, bilateral 50 cases Ambras syndrome 40 cases Anorectal malformation 24 Amelia, autosomal recessive 3 cases Anosmia, isolated, congenital < 15 cases Amelo-cerebro-hypohidrotic 19 cases syndrome Antisynthetase syndrome 1.5 Aminopterin embryofetopathy 17 cases Antley-Bixler syndrome 34 cases

** Prevalence at birth

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data November 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Number 1 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Antley-Bixler-like syndrome - < 50 cases Astley-Kendall dysplasia < 10 cases ambiguous genitalia - disordered steroidogenesis Ataxia - apraxia - mental retardation, 9 cases X-linked Aortic aneurysm syndrome, Loeys- 10 families Dietz type Ataxia - deafness - optic atrophy, 12 cases lethal Aortic arch anomaly - peculiar 4 cases facies - mental retardation Ataxia telangiectasia 1 Aortic arch interruption 0.3** Ataxia, autosomal recessive, Beauce 57 cases Aortic dilatation- joint 22 cases type hypermobility- arterial tortuosity Ataxia, cerebellar, autosomal 2.15 Aorto-ventricular tunnel 130 cases dominant Apert syndrome 1.25 Ataxia, cerebellar, autosomal 3 families Aphalangy - hemivertebrae - 3 cases recessive - blindness - deafness urogenital-intestinal dysgenesis Ataxia, cerebellar, autosomal 1 family Aphalangy - syndactyly - 1 family recessive - saccadic intrusion microcephaly Ataxia, episodic, type 3 1 family Aplasia cutis - myopia 4 cases Ataxia, episodic, type 4 2 families Aplasia cutis congenita - intestinal 3 cases lymphangiectasia Ataxia, spinocerebellar, X-linked, 5 cases Aplasia cutis congenita of limbs 6 cases type 3 recessive Ataxia-deafness-retardation 8 cases Aplastic anaemia 0.4 syndrome Arachnodactyly - mental 3 cases Atelosteogenesis I 12 cases retardation - dysmorphism Atelosteogenesis, type II 25 cases Arachnodactyly - ossification 5 cases abnormal - mental retardation Atelosteogenesis, type III 12 cases Athabaskan brainstem dysgenesis 10 cases AREDYLD syndrome 3 cases syndrome Argininemia 31 cases Atherosclerosis- deafness - 2 cases Arhinia - choanal atresia - 4 cases diabetes - epilepsy - nephropathy microphthalmia Atkin-Flaitz syndrome 14 cases Aromatase deficiency 13 cases Atransferrinemia 9 cases Arrhinia 20 cases Atresia of small intestine 20 Arrhythmogenic right ventricular 43.5 dysplasia Atrial septal defect - atrioventricular 11 cases Arterial dissection - lentiginosis 4 cases conduction defects Arterial tortuosity < 40 cases Atrial tachyarrhythmia with short PR 12 cases interval Arthritis, enthesitis-related 5.7 Atrioventricular canal, complete 15** Arthritis, juvenile psoriatic 4.2 Atrioventricular canal, partial 20 Arthritis, oligoarticular juvenile 20.5 Atypical coarctation of aorta 0.17** Arthritis, systemic-onset, juvenile 6.3 idiopathic Aughton syndrome 2 cases Arthrogryposis - hyperkeratosis, 2 cases Auricular abnormalities - cleft lip 2 cases lethal form with or without cleft palate - ocular abnormalities Arthrogryposis - renal dysfunction - < 150 cases cholestasis Auriculoocular anomalies - cleft lip 2 cases Arthrogryposis multiplex congenita 30 Auriculoosteodysplasia 2 families Arthrogryposis multiplex congenita - 10 cases Aurocephalosyndactyly 5 cases whistling face Autism 45 Arthrogryposis-like hand anomaly - 1 family Autism - facial port-wine stain 4 cases sensorineural deafness Autoimmune lymphoproliferative 100 cases Ascher syndrome 50 cases syndrome

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Autoimmune polyendocrinopathy, 4 Bone dysplasia - corpus callosum 1 case type 1 agenesis Axenfeld-Rieger anomaly - 3 cases Bone dysplasia, Azouz type 1 case hydrocephaly - skeletal abnormalities Bone dysplasia, lethal, Holmgren 4 cases Babesiosis 40 cases type Bacterial toxic-shock syndrome 3 Bone fragility - craniosynostosis - 4 cases proptosis - hydrocephalus Bakrania-Ragge syndrome 2 families Bone tumour 10 Ballard syndrome 12 cases Bonnemann-Meinecke-Reich 4 cases Bamforth syndrome 5 cases syndrome Bangstad syndrome 2 cases Book syndrome 25 cases Banki syndrome 1 family Boomerang dysplasia 10 cases Barber-Say syndrome 10 cases BOR syndrome 2.5 Bardet-Biedl syndrome 0.8 Bosley-Salih-Alorainy syndrome 9 cases Bartsocas-Papas syndrome 24 cases Botulism 0.05 Bartter syndrome 0.12 Boutonneuse fever 17 Beckwith-Wiedemann syndrome 7.3 Bouwes-Bavinck syndrome 2 cases Beemer-Ertbruggen syndrome 2 cases Bowen-Conradi syndrome 44 cases Behcet disease 2.5 Brachydactyly - arterial hypertension > 10 families

Bencze syndrome 2 families Brachydactyly - long thumb 4 cases Benign exophthalmos syndrome 4 cases Brachydactyly - nystagmus - 1 family cerebellar ataxia Benign paroxysmal torticollis of 50 cases infancy Brachydactyly - preaxial hallux varus 8 cases Bernard-Soulier syndrome 100 cases Brachydactyly, type A5 2 families Best disease 4.4 Brachydactyly, type A7 1 family Beta-mannosidosis 14 cases Brachymorphism - onychodysplasia - 9 cases dysphalangism Beta-sarcoglycanopathy 0.57 Brachytelephalangy - dysmorphism - 2 cases Beta-ureidopropionase deficiency 5 cases Kallmann syndrome Bethlem myopathy 100 cases Braddock syndrome 2 cases Bickel-Fanconi glycogenosis 112 cases Bradyopsia 5 cases Bile acid synthesis defect, 4 cases Brain dysgenesis due to glutamine 2 cases congenital, type 4 synthetase deficiency, congenital Biliary atresia 5.6 Brain malformation - congenital 2 cases Biliary tract malformation - renal 6 cases heart disease - postaxial polydactyly failure Branchiogenic deafness syndrome 5 cases Birt-Hogg-Dube syndrome 0.5 Branchio-oculo-facial syndrome < 50 cases Björnstad syndrome 33 cases Branchio-skeleto-genital syndrome 3 cases Blackfan-Diamond disease 0.32 Breast cancer, familial 25 Blaichman syndrome 1 case Bronchobiliary fistula, congenital 23 cases Blepharo-cheilo-dontic syndrome < 50 cases Bronchopneumopathy, chronic, due < 20 cases Blepharo-facio-skeletal syndrome 2 cases to TAP deficiency Blepharonasofacial malformation 2 families Bronchopulmonary dysplasia 13 syndrome Brown-Vialetto-van Laere syndrome < 100 cases Blepharophimosis - ptosis - 6 cases Bruck syndrome < 40 cases esotropia - syndactyly - short stature Budd-Chiari syndrome 1.5 Blepharoptosis - myopia - ectopia 3 cases lentis Buerger’s disease 12.5 Bloom syndrome > 100 cases Bullous dystrophy, macular type 2 families Blue rubber bleb nevus > 200 cases Bullous pemphigoid 2.5

** Prevalence at birth

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Buttiens-Fryns syndrome 3 cases Carpenter syndrome 40 cases CACH syndrome 148 cases Carpotarsal osteochondromatosis < 10 cases CADASIL 500 cases Carpotarsal osteolysis, recessive < 10 cases Calpainopathy 3.8 Castleman disease 400 cases Calvarial doughnut lesions - bone 20 cases Cataract - deafness - hypogonadism 3 cases fragility Cataract - hypertrichosis - 1 case CAMFAK syndrome 3 families intellectual deficit CAMOS syndrome 5 cases Cataract - mental retardation - 10 cases hypogonadism Campomelia, Cumming type 8 cases Cataract - microphthalmia - septal 2 cases Campomelic dysplasia 0.35 defect Camptobrachydactyly 1 family Cataract - nephropathy - 2 cases Camptodactyly - fibrous tissue 3 cases encephalopathy hyperplasia - skeletal dysplasia Cataract- ataxia - deafness 2 cases Camptodactyly - tall stature - 30 cases Cataract cardiomyopathy 30 cases scoliosis - hearing loss Camptodactyly - taurinuria 4 families Cataract-glaucoma 3 families Camptodactyly syndrome, 8 cases Cataract-microcornea syndrome 8 families Guadalajara type 1 Cataracts, congenital - facial 100 cases Camptodactyly syndrome, 2 cases dysmorphism - neuropathy Guadalajara type 2 Catel-Manzke syndrome 27 cases Camurati-Engelmann disease 200 cases Cat-eye syndrome 1.35 Cantrell pentalogy 0.55** Cat-scratch disease 6.6 Capillary leak syndrome 57 cases Cavitating leukoencephalopathy, 19 cases Carbamoylphosphate synthetase 0.7 progressive deficiency CDG syndrome 1.5** Carcinoma of the gallbladder 6.5 CDG syndrome, type Ia 300 cases Cardiac anomalies - heterotaxy 9 cases CDG syndrome, type Ib 20 cases Cardiac anomalies - heterotaxy 9 cases CDG syndrome, type Ic > 30 cases Cardiac conduction disease, dilated 10 cases CDG syndrome, type Id 5 cases cardiomyopathy and brachydactyly CDG syndrome, type Ie 7 cases Cardiocranial syndrome, Pfeiffer type < 10 cases CDG syndrome, type If 4 cases Cardiogenital syndrome 7 cases CDG syndrome, type Ig 6 cases Cardiomyopathy - cataract - hip 9 cases CDG syndrome, type Ih 5 cases spine disease CDG syndrome, type Ii 1 case Cardiomyopathy - renal anomalies 2 cases CDG syndrome, type IIa 4 cases Cardiomyopathy, familial dilated 17.5 CDG syndrome, type IIb 1 case Cardiomyopathy-exercise intolerance 3 cases CDG syndrome, type IId 1 case due to muscle and heart glycogen deficiency CDG syndrome, type IIe 2 cases Carey-Fineman-Ziter syndrome < 20 cases CDG syndrome, type IIh 2 cases Carney complex 160 cases CDG syndrome, type Ij 1 case Carney triad 100 cases CDG syndrome, type Ik 4 cases Carnitine palmitoyl transferase 1 35 cases CDG syndrome, type IL 2 cases deficiency CEDNIK syndrome 7 cases Carnitine palmitoyl transferase 2 > 100 cases Celiac disease - epilepsy - occipital 170 cases deficiency calcifications Carnitine-acylcarnitine translocase 30 cases Central neurocytoma > 100 cases deficiency Cerebellar ataxia - areflexia - pes 2 families Carnosinemia 30 cases cavus - optic atrophy - sensorineural Caroli’s disease < 250 cases hearing loss

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Cerebellar ataxia, autosomal 7 Choroidal atrophy - alopecia 2 cases recessive Choroidal dystrophy, central areolar 3.33 Cerebral arteriovenous fistula 6 Choroideremia 2 Cerebral gigantism - jaw cysts < 10 cases Choroideremia - deafness - obesity 4 cases Cerebro-costo-mandibular syndrome 60 cases Choroido cerebral calcification 10 cases Cerebro-oculo-nasal syndrome 10 cases syndrome, infantile form Cerebroretinal vasculopathy 3 families Christ-Siemens-Touraine syndrome 0.35 Ceroid lipofuscinosis, neuronal 4 Chromosome Y deletion 42 Cervical hypertrichosis - peripheral 3 cases Chronic hiccup 1 neuropathy Chronic inflammatory demyelinating 4.4 CHAND syndrome > 10 cases polyneuropathy Chaotic atrial tachycardia 100 cases Chronic recurrent multifocal > 260 cases Char syndrome 10 cases osteomyelitis, juvenile Charcot-Marie-Tooth disease 32.5 Churg-Strauss syndrome 1 Charcot-Marie-Tooth disease - 10 cases Chylomicron retention disease 40 cases nephropathy CINCA syndrome 100 cases Charcot-Marie-Tooth disease, type 1 family Cleft lip - retinopathy 2 cases 2B2 Cleft lip/mandibule, median 70 cases Charcot-Marie-Tooth disease, type 2 families 2F, autosomal dominant Cleft lip/palate - intestinal 4 cases malrotation - cardiopathy Charcot-Marie-Tooth disease, type 1 family 2G, autosomal dominant Cleft lip/palate - mental 2 cases retardation - corneal opacities Charcot-Marie-Tooth disease, type 1 family Cleft palate - cardiac defect - genital 5 cases 2K, autosomal dominant anomalies - ectrodactyly Charcot-Marie-Tooth disease, type 1 family Cleft palate - short stature - 2 cases 2L, autosomal dominant vertebral anomalies Charcot-Marie-Tooth disease, type 4J 4 cases Cleft palate - stapes fixation - 2 cases Charcot-Marie-Tooth disease, X- 1.6 oligodontia linked Cleft palate-lateral synechia 7 cases CHARGE syndrome 0.14 syndrome Chediak-Higashi syndrome > 10 cases Cleido rhizomelic syndrome 2 cases CHILD syndrome 30 cases Clouston syndrome 1 Choanal atresia 8.2 Cloverleaf skull syndrome 150 cases Choanal atresia - deafness - cardiac 5 cases COACH syndrome 8 cases defects - dysmorphism Coats disease 2 Cholangiocarcinoma 10 Cobb syndrome 35 cases Cholestasis - lymphoedema 50 cases Cockayne syndrome 200 cases Cholestasis pigmentary - 5 cases Coffin-Lowry syndrome 0.55 retinopathy - cleft palate Coffin-Siris syndrome 40 cases Cholesteryl ester storage disease < 50 cases Cogan syndrome 200 cases Chondrodysplasia - disorder of sex 2 cases development Cohen syndrome 100 cases Chondrodysplasia - situs inversus - 1 case Collagenous colitis 10.5 imperforate anus - polydactyly Coloboma of macula - brachydactyly 12 cases Chondrodysplasia punctata, 1 type B rhizomelic type Coloboma uveal - cleft lip palate - 12 cases Chondrodysplasia, Blomstrand type 13 cases intellectual deficit Chondrodysplasia, lethal recessive 4 cases Coloboma, ocular 1 Chordoma 0.05 Colobomatous - microphthalmia - 10 cases heart disease - hearing loss Chorioretinal atrophy, progressive 2 families bifocal Cone rod dystrophy 2.5

** Prevalence at birth

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Cone rod dystrophy - amelogenesis 29 cases Craniorhiny 3 families imperfecta Craniosynostosis - dysmorphism - 5 cases Contractures - ectodermal dysplasia - 2 cases brachydactyly cleft lip/palate Craniosynostosis - fibular aplasia 2 cases Cooper-Jabs syndrome 2 cases Craniosynostosis - intracranial 3 cases Corneal anesthesia - deafness - 2 cases calcifications mental retardation Craniosynostosis dandy walker 4 cases Corneal dystrophy - ichthyosis - 1 case hydrocephalus microcephaly - mental retardation Craniosynostosis, Boston type 19 cases Corneal dystrophy - perceptive < 10 cases deafness Craniosynostosis, Philadelphia type 1 family Corneal-cerebellar syndrome 2 cases Craniosynostosis-radial aplasia, 2 cases Imaizumi type Cornelia de Lange syndrome 5.25 Creutzfeldt-Jakob disease 0.1 Coronary artery disease - 1 family hyperlipidemia - hypertension - Crigler-Najjar syndrome 1 diabetes - osteoporosis Crisponi syndrome < 30 cases Corpus callosum agenesis 19 Criss-cross heart 0.8 neuronopathy Crouzon disease 2 Corpus callosum dysgenesis, X-linked 11 cases recessive Cryptomicrotia - brachydactyly - 2 cases excess fingertip arch Corpus callosum, agenesis - 8 cases cataract - immunodeficiency Cryptosporidiosis 34 Cortical blindness - mental 3 cases Curry-Jones syndrome 5 cases retardation - polydactyly Cutaneous albinism, ermine 3 cases Corticobasal degeneration 4 phenotype Corticosteroid-sensitive aseptic 49 cases Cutaneous lymphomas 8.3 abscesses Cutaneous neuroendocrine carcinoma 0.5 Costello syndrome 200 cases Cutaneous photosensitivity - colitis, 3 cases Costocoracoid ligament, congenitally 1 family lethal short Cutis gyrata - acanthosis nigricans - 6 cases Cowden syndrome 0.45 craniosynostosis Coxoauricular syndrome 4 cases Cutis laxa > 100 cases Coxo-podo-patellar syndrome 47 cases Cutis marmorata telangiectatica 300 cases congenita Cranio osteoarthropathy 4 cases Cutis verticis gyrata - intellectual 1.02 Craniodiaphyseal dysplasia > 20 cases deficit Craniodiaphyseal dysplasia, 2 cases Cyprus facial-neuromusculoskeletal 1 family autosomal dominant 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 dysmorphism - 3 cases coloboma - corpus callosum agenesis Cystic hygroma, lethal - cleft palate 2 cases Craniofacial dyssynostosis 0.05 Cystinosis 0.5 Craniofacial-deafness-hand syndrome 3 cases Cystinuria 14 Craniofaciocardioskeletal syndrome 4 cases Cystoid macular dystrophy 6 families Craniofrontonasal dysplasia - Poland 3 cases Czech dysplasia, metatarsal type < 20 cases anomaly Dacryocystitis - osteopoikilosis 5 cases Craniofrontonasal dysplasia, Teebi 20 cases Dahlberg-Borer-Newcomer syndrome 2 cases type Dandy-Walker malformation - 2 cases Craniolenticulosutural dysplasia 28 cases macrocephay Craniometaphyseal dysplasia 70 cases Dandy-Walker malformation - 2 cases Craniopharyngioma 2 polydactyly, postaxial

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Darier disease 1.5 Developmental malformations - 2 cases deafness - dystonia Deaf blind hypopigmentation 2 cases syndrome, Yemenite type Diabetes insipidus, nephrogenic 0.5 Deafness - enamel hypoplasia - nail 6 cases Diabetes mellitus, neonatal 0.2 defects Diabetes mellitus, permanent 4 cases Deafness - genital anomalies - 2 cases neonatal - pancreatic and cerebellar metacarpal and metatarsal agenesis synostosis Diabetes, neonatal - congenital 2 cases Deafness - lymphoedema - leukaemia < 10 cases hypothyroidism - congenital glaucoma - hepatic fibrosis - Deafness - opticoacoustic nerve 3 cases polycystic kidneys atrophy - dementia Diaphanospondylodysostosis < 10 cases Deafness - peripheral neuropathy - 4 cases arterial disease Diaphragmatic defect - limb 4 cases deficiency - skull defect Deafness - skeletal dysplasia - lip 8 cases granuloma Diaphragmatic hernia - exomphalos - 13 cases corpus callosum agenesis Deafness - vitiligo - achalasia 2 cases Diaphragmatic hernia, congenital 15 Deafness-infertility syndrome 3 families Diastrophic dwarfism 3.5 Deafness-mental retardation, Martin- 3 cases Probst type Diffuse leiomyomatosis - Alport 0.1 syndrome X-linked Deafness-mental retardation, Martin- 3 cases Probst type Diffuse neonatal haemangiomatosis < 70 cases Deafness-tubular acidosis-anaemia 2 cases Diffuse palmoplantar keratoderma - 10 cases acrocyanosis Defective expression of HLA class 2 100 cases Digitorenocerebral syndrome < 10 cases Dehydratase deficiency 21 cases Digitotalar dysmorphism 6 Deletion 2q24 23 cases Dihydropteridine reductase 134 cases Deletion 2q37 10 cases deficiency Delta-sarcoglycanopathy 0.57 Dihydropyrimidinuria 7 cases DEND syndrome 14 cases Dincsoy-Salih-Patel syndrome 2 cases Dentatorubral pallidoluysian atrophy < 0.3 Distal monosomy 10q 40 cases Dentinogenesis imperfecta - short 2 cases Distal monosomy 5q 10 cases stature - hearing loss - mental Distal monosomy 8p 20 cases retardation Distal myopathy with posterior leg 12 cases Denys-Drash syndrome 150 cases and anterior upper limb involvement Depigmentation of the iris, acute, 5 cases Distal myopathy with vocal cord 12 cases bilateral weakness Dermatitis herpetiformis 20.2 Distal myopathy, Nonaka type 0.1 Dermato-cardio-skeletal syndrome, 2 cases Borrone type Distal myopathy, Welander type 10 Distal myopathy, with early 24 cases Dermatofibrosarcoma protuberans 10 respiratory muscle involvement Dermatoleukodystrophy 2 cases DOOR syndrome < 50 cases Dermatomyositis 14.8 Dopamine beta-hydroxylase 12 cases Dermatoosteolysis, Kirghizian type 5 cases deficiency Dermo-odonto dysplasia 14 cases Double outlet left ventricle 32 cases Dermopathy restrictive, lethal 30 cases Double uterus-hemivagina-renal < 60 cases Desbuquois syndrome > 40 cases agenesis Desmosterolosis 2 cases Duane anomaly - myopathy - 2 cases scoliosis Developmental delay due to 2- < 30 cases Duane syndrome 10 methylbutyryl-CoA dehydrogenase deficiency Dubowitz syndrome 150 cases Developmental dysphasia familial 6 families Duker-Weiss-Siber syndrome 4 cases

** Prevalence at birth

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data November 2008 10 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Number 1 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of diseases

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Duodenal atresia 8.55 Ehlers-Danlos syndrome, type 3 12.5 Dyggve-Melchior-Clausen disease 60 cases Ehlers-Danlos syndrome, type 4 1 Dyschondrosteosis - nephritis 1 family Ehlers-Danlos syndrome, type 5 2 families Dyserythropoietic anaemia, 1 Ehlers-Danlos syndrome, type 7C 7 cases congenital Ehrlichiosis < 50 cases Dyskeratosis congenita 0.1 Eiken syndrome 6 cases Dysmorphism - short stature - 2 cases Elejalde syndrome 30 cases deafness - pseudohermaphroditism Elliptocytosis, hereditary 35 Dysplasia, mandibuloacral 37 cases Ellis Van Creveld syndrome 150 cases Dystonia, dopa-responsive 0.3 Emery-Dreifuss muscular dystrophy 0.3 Dystonia, mixed 3 families Encephalocraniocutaneous 45 cases Earlobes, thickened - conductive 2 families lipomatosis deafness Encephalopathy due to < 30 cases Early infantile epileptic 88 cases hydroxykynureninuria encephalopathy Encephalopathy due to prosaposin < 10 cases Early myoclonic encephalopathy 30 cases deficiency Early onset torsion dystonia 0.4 Encephalopathy due to sulphite 50 cases Ear-patella-short stature syndrome 42 cases oxidase deficiency Ebstein anomaly 0.75 Encephalopathy with neuroserpin > 5 families inclusion bodies, familial form Ectodermal dysplasia - absent < 30 cases dermatoglyphs Encephalopathy, ethylmalonic < 40 cases Ectodermal dysplasia - anhidrotic, 2 cases Enchondromatosis 600 cases with immunodeficiency - Endosteal sclerosis - cerebellar 4 cases osteopetrosis - lymphoedema hypoplasia Ectodermal dysplasia - 1 case Eng-Strom syndrome 2 cases arthrogryposis - diabetes mellitus Enterocyte heparan sulphate 3 cases Ectodermal dysplasia - blindness 2 cases deficiency, congenital Ectodermal dysplasia - skin fragility 10 cases Eosinophilic fasciitis 200 cases syndrome Ectodermal dysplasia, Berlin type 4 cases Eosinophilic gastroenteritis 280 cases Ectodermal dysplasia, hidrotic, 6 cases Eosinophilic pneumonia, acute, > 100 cases Christianson-Fourie type idiopathic Ectodermal dysplasia, hidrotic, Halal 4 cases Epidermal nevus syndrome > 400 cases type Epidermolysis bullosa simplex - limb < 20 cases Ectodermal dysplasia, hypohidrotic - 3 cases girdle muscular dystrophy hypothyroidism - ciliary dyskinesia Epidermolysis bullosa, acquired 100 cases Ectodermal dysplasia, hypohidrotic, 40 cases Epidermolysis bullosa, dystrophic 0.27 autosomal dominant Epidermolysis bullosa, epidermolytic 2.5 Ectodermal dysplasia, ‘’pure’’ hair- < 20 cases nail type Epidermolysis bullosa, junctional 0.06 Epilepsy - microcephaly - skeletal 2 cases Ectodermic dysplasia hypothyroidism 3 cases dysplasia cleft Epilepsy telangiectasia 6 cases Ectopia lentis - chorioretinal 4 cases dystrophy - myopia Epilepsy, pyridoxin-dependent 0.15 Ectopia lentis isolated 6.4 Epiphyseal dysplasia multiple 5 Ectrodactyly - ectodermal dysplasia 5 cases Epithelio-exfoliative colitis - 2 cases without clefting deafness EEM syndrome 7 families Erdheim-Chester disease 178 cases Ehlers-Danlos syndrome, classic type 3.5 Erythermalgia, primary 30 families Ehlers-Danlos syndrome, 6 cases Erythroderma, congenital 0.4 spondylocheiro dysplastic form ichthyosiform, bullous Ehlers-Danlos syndrome, type 10 1 family Erythroderma, lethal, congenital 17 cases

** Prevalence at birth November 2008 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data 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

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Erythrokeratodermia ataxia 25 cases Fibrodysplasia ossificans progressiva 0.08 Erythrokeratodermia variabilis, > 200 cases Fibrous dysplasia of bone < 0.05 Mendes da Costa type Fibular aplasia - ectrodactyly < 50 cases Esophageal atresia 25 Fibular dimelia - diplopodia 11 cases Esophageal carcinoma 8 Filippi syndrome < 25 cases Esthesioneuroblastoma < 1000 cases Fine-Lubinsky syndrome 5 cases Evans syndrome 0.1 Fingerprints, absence of - milia, 14 cases Ewing sarcoma 0.1 congenital Excessive growth - learning 6 families Floating-Harbor syndrome < 50 cases disabilities - facial dysmorphism Flynn-Aird syndrome 10 cases Exostoses, multiple 2 Focal dermal hypoplasia 300 cases Eyebrow duplication - syndactyly 3 cases Focal dystonia 11.7 Fabry disease 1.75 Focal facial dermal dysplasia < 10 families Facial dysmorphism - macrocephaly - 3 cases Focal myositis 50 cases myopia - Dandy-Walker malformation Folate malabsorption, hereditary 17 cases Facial onset sensory and motor 4 cases neuronopathy Follicular lymphoma 36 Faciocardiomelic dysplasia, lethal 3 cases Foveal hypoplasia - presenile 11 cases cataract Facioscapulohumeral muscular 7 dystrophy Fragile X syndrome 14.25 Factor II deficiency 10 Frank-Ter Haar syndrome 5 cases Factor V deficiency 0.1 Fraser syndrome 150 cases Factor VII deficiency 0.25 Freeman-Sheldon syndrome 100 cases Factor XI deficiency, congenital 0.1 Fried syndrome 1 family Factor XIII deficiency, congenital 0.04 Friedreich ataxia 2.5 Fahr syndrome < 20 families Frontometaphyseal dysplasia < 30 cases Familial adenomatous polyposis 5.25 Frontotemporal dementia 3 Familial caudal dysgenesis 4 cases Fronto-temporal dementia and 50 cases Parkinsonism linked to chromosome Familial cold urticaria 0.1 17 (FTDP-17) Familial dysautonomia 550 cases Fructose intolerance 5 Familial hematuria, autosomal 8 cases Fructose-1,6-bisphosphatase 2.5 dominant - retinal arteriolar deficiency tortuosity - contractures Fryns syndrome 7** Familial platelet syndrome with < 20 families predisposition to acute myelogenous Fucosidosis 100 cases leukaemia Fuhrmann syndrome 11 cases Familial platelet syndrome with 13 families Fumaric aciduria > 20 cases predisposition to acute myelogenous leukaemia Fuqua-Berkovitz syndrome 2 cases Galactosemia 6.6 Fanconi anaemia 1 Galloway-Mowat syndrome 40 cases Fanconi ichthyosis dysmorphism 6 cases Gamma aminobutyric acid 2 cases Fanconi syndrome 100 cases transaminase deficiency Femur bifid - monodactylous - 200 cases Gamma-glutamyl transpeptidase 7 cases ectrodactyly deficiency Femur-fibula-ulna complex 1.5 Gamma-glutamylcysteine synthetase 9 cases Fetal cytomegalovirus syndrome 40 deficiency Fetal methyl mercury syndrome 800 cases Gamma-sarcoglycanopathy 1.96 Fetal varicella syndrome > 100 cases GAPO syndrome 27 cases Fibrinogen deficiency, congenital 0.15 Gardner-Morrison-Abbott syndrome 3 cases Fibrochondrogenesis 11 cases Gastric cancer 20

** Prevalence at birth

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Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Gastrointestinal stromal tumour 13 Goodpasture syndrome 0.64 Gastroschisis 12 Gorham-Stout disease 200 cases Gaucher disease 2 Gorlin syndrome 1 Gaucher disease - ophthalmoplegia - < 10 cases Gorlin-Chaudhry-Moss syndrome 4 cases cardiovascular calcification GRACILE syndrome 2.12** Gaucher disease, type 1 0.94 Graft versus host disease 3.4 Gaucher disease, type 2 0.01 Grange syndrome 6 cases Gaucher disease, type 3 0.05 Granulomatous arthritis of childhood 40 families Geleophysic dwarfism 27 cases Granulomatous disease, chronic 0.2 Generalised resistance to 2 cases Granulomatous slack skin < 50 cases thyrotropin-releasing hormone Gräsbeck-Imerslund disease 300 cases Genitopatellar syndrome 7 cases Gray platelet syndrome 20 cases German syndrome 5 cases Greenberg dysplasia < 10 cases Geroderma osteodysplastica 30 cases Greig syndrome 100 cases Giant cell arteritis 8.9 Griscelli disease 60 cases Giant pigmented hairy nevus 2 Growth deficiency - brachydactyly - 2 families Gingival fibromatosis - progressive 2 families dysmorphism deafness Growth delay - intellectual 4 cases Gitelman syndrome 2.5 deficit - mandibulofacial dysostosis - Glaucoma - ectopia - 3 cases microcephaly - cleft palate microspherophakia - stiff joints - Growth delay due to insulin-like 4 cases short stature growth factor I deficiency Glaucoma - sleep apnoea 5 cases Growth retardation - microcephaly - 4 cases Glioblastoma 11 digital abnormalities - hypospadias Global developmental delay - 3 cases GTP cyclohydrolase I deficiency 17 cases osteopenia - ectodermal defect Guanidinoacetate methyltransferase 9 cases Glomerulonephritis - sparse hair - < 10 cases deficiency telangiectasis Guillain-Barré syndrome 3.45 Glucocorticoid deficiency, familial 50 cases Haemolytic anaemia due to 12 cases Glucose-galactose malabsorption 200 cases adenylate kinase deficiency Glucosephosphate isomerase 50 cases Haemolytic anaemia due to 3 cases deficiency glutathione reductase deficiency Glutaryl-CoA dehydrogenase 0.4 Haemolytic anaemia, due to red cell 0.4 deficiency pyruvate kinase deficiency Glutathione synthetase deficiency 65 cases Haemolytic anaemia, lethal - genital 2 cases anomalies Glycogen storage disease due to 84 cases LAMP-2 deficiency Haemolytic anaemia, nonspherocytic, 17 families due to hexokinase deficiency Glycogen storage disease type 2 1.1 Hair defect - photosensitivity - 3 cases Glycogen storage disease type 4 0.6 mental retardation Glycogen storage disease type 7 < 30 cases Hallermann-Streiff-Francois < 100 cases Glycogen storage, 0 type 16 cases syndrome Goldberg-Shprintzen megacolon 10 cases Harding ataxia 1 syndrome Hartnup syndrome 4 Goldenhar syndrome 3.5 Hartsfield-Bixler-Demyer syndrome 6 cases Goldmann-Favre syndrome < 50 cases Heart defects - limb shortening 2 cases Gombo syndrome 4 cases HEC syndrome 2 cases Gonadal dysgenesis, XX type 12 Helicoid peripapillary chorioretinal 100 cases Gonadal dysgenesis, XY type - 2 cases degeneration associated anomalies Hemicrania, paroxysmal 2 Goodman syndrome 3 cases Hemimelia 4.15

** Prevalence at birth November 2008 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data 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

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Hemiplegic migraine, familial or 10 Hyaluronidase deficiency 1 case sporadic Hydrocephalus - blue sclerae - 1 family Hemochromatosis, neonatal 100 cases nephropathy Hemophilia 7.7 Hydrocephalus - costovertebral 8 cases dysplasia - Sprengel anomaly Hemophilia, acquired 0.1 Hydrocephaly - tall stature - joint 2 cases Hemorrhagic disorders due to < 20 cases laxity collagen receptors deficiency Hydrolethalus 5** Hennekam syndrome > 50 cases Hypercoagulability syndrome, due 2 cases Hennekam-Beemer syndrome 2 cases to glycosylphosphatidylinositol Henoch-Schoenlein purpura 8.5 deficiency Hepatic venoocclusive disease 11 Hyperferritinemia, hereditary, with > 64 cases Hepatic veno-occlusive disease - < 25 cases congenital cataracts immunodeficiency Hyperglycinemia, isolated nonketotic 0.2 Hepatitis, chronic autoimmune 0.75 Hyperimmunoglobinemia D with 180 cases Hereditary inclusion body 19 cases recurrent fever myopathy - joint contractures - Hyperkalemic periodic paralysis 0.75 ophthalmoplegia Hyperkeratosis - hyperpigmentation 10 cases Hereditary vascular retinopathy 1 family syndrome Hereditary vascular retinopathy 1 family Hyperlipidemia type 3 7.8 Hermansky-Pudlak syndrome 0.15 Hyperlipoproteinemia type 1 0.6 HERNS syndrome 3 families Hyperostotic dwarfism, Lenz- 7 cases Hersh-Podruch-Weisskopf syndrome 2 cases Majewski type Heterotaxia 2.5 Hyperoxaluria 0.2 Hirschsprung disease 20 Hyperplastic polyposis syndrome 50 Hirschsprung disease - deafness - 2 cases Hypertrichosis cubiti - short stature 28 cases polydactyly Hypertrichosis lanuginosa congenita < 100 cases Hirschsprung disease - nail 3 cases Hypertrichosis lanuginosa, acquired 60 cases hypoplasia - dysmorphism Hypertrichosis, anterior cervical, < 20 cases Hirschsprung disease - type D 4 cases isolated brachydactyly Hypertrichotic osteochondrodysplasia 18 cases Histidinemia 4 Hypochondroplasia 3.3 Histiocytosis, progressive mucinous, 13 cases Hypocomplementaemic < 100 cases hereditary leucocytoclasic vasculitis Histiocytosis, sea-blue 60 cases Hypogammaglobulinemia due to 4 cases Histiocytosis, sinus, with massive 500 cases CD19 deficiency lymphadenopathy Hypoglossia - hypodactyly < 50 cases Hodgkin lymphoma, classical 10.5 Hypogonadism - retinitis pigmentosa 3 cases Holoprosencephaly 7 Hypokalemic periodic paralysis 1 Holt-Oram syndrome 1 Hypomagnesemia with hypocalciuria 3 families Homocarnosinosis 4 cases Hypomagnesemia with 2 cases Homocystinuria due to cystathionine 0.4 normocalciuria beta-synthase deficiency Hypomandibular faciocranial 4 cases Homocystinuria without 60 cases dysostosis methylmalonic aciduria Hypomyelination - congenital 8 cases Humeroradial synostosis 150 cases cataract Humeroradioulnar synostosis 30 cases Hypomyelination - hypogonadotropic 4 cases hypogonadism - hypodontia Humerospinal dysostosis 5 cases Hypomyelination - hypogonadotropic 4 cases Humeroulnar synostosis 5 cases hypogonadism - hypodontia Huntington disease 6.2 Hypomyelination with atrophy of 19 cases Hyaline fibromatosis, juvenile 50 cases basal ganglia and cerebellum

** Prevalence at birth

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Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Hypoparathyroidism - deafness - 12 cases Immunodeficiency due to < 15 cases renal disease interleukin-1 receptor-associated kinase-4 deficiency Hypoparathyroidism, familial, < 10 families isolated Immunodeficiency due to selective 100 cases anti-polysaccharide antibody Hypoparathyroidism, X-linked 2 families deficiency Hypopituitarism - microphthalmia < 10 cases Immunodeficiency with natural-killer 4 cases Hypopituitarism - postaxial 6 cases cell deficiency polydactyly Immunodeficiency, common variable 7.5 Hypospadias-hypertelorism-coloboma 2 cases Inappropriate antidiuretic hormone 2 cases and deafness secretion syndrome Hypotelorism - cleft palate - 13 cases Inclusion body myositis, IBM 0.49 hypospadias Incontinentia pigmenti 0.2 Hypothyroidism - dysmorphism - 5 cases Indifference to pain, congenital 20 cases postaxial polydactyly - intellectual deficit Infant epilepsy with migrant focal 29 cases crisis Hypothyroidism, congenital 29 Infantile neuroaxonal dystrophy > 150 cases Hypotonia with lactic acidaemia and 3 cases hyperammonaemia Inflammatory pseudotumour of the 143 cases liver Hypotrichosis - lymphoedema - 4 cases telangiectasia Insomnia, familial fatal 27 cases Hypotrichosis simplex 38 cases Insulin resistance, short fifth 1 family metacarpals Hypotrichosis-mental retardation, 2 cases Intellectual deficit, severe - 2 cases Lopes type epilepsy - anal anomalies - distal IBIDS syndrome 15 cases phalangeal hypoplasia ICF syndrome 50 cases Internal carotid agenesis 100 cases Ichthyosis - alopecia - eclabion - 4 cases Interstitial granulomatous dermatitis < 20 cases ectropion - mental retardation with arthritis Ichthyosis - hepatosplenomegaly - 2 cases Intractable diarrhoea - choanal 3 cases cerebellar degeneration atresia - eye anomalies Ichthyosis - male hypogonadism 5 cases Intrauterine infection-like syndrome, > 30 cases congenital Ichthyosis - oral and digital 2 cases Iris coloboma with ptosis - 10 cases anomalies intellectual deficit Ichthyosis bullosa of Siemens < 20 cases Iris dysplasia - hypertelorism - 2 cases Ichthyosis congenita - biliary atresia 2 cases deafness Ichthyosis congenita, harlequin type < 100 cases Isolated brachycephaly 5 Ichthyosis follicularis - atrichia - 10 cases Isolated plagiocephaly 10 photophobia Isolated scaphocephaly 20 Ichthyosis prematurity syndrome 16 families Isolated trigonocephaly 6.7 Ichthyosis, congenital - 2 cases Isotretinoin-like syndrome 6 cases microcephalus - quadriplegia Isovaleric acidemia 1 Ichthyosis, lamellar > 0.33 IVIC syndrome 4 families Ichthyosis, X-linked 16.6 Jackson-Weiss syndrome 2 families Idiopathic hypereosinophilic 10 Jacobsen syndrome 150 cases syndrome Jeune syndrome 0.2 Idiopathic hypersomnia 4 Job syndrome 250 cases IMAGe syndrome < 20 cases Johanson-Blizzard syndrome 23 cases Iminoglycinuria 6.68 Joubert syndrome 0.85 Immune dysregulation - 7 families polyendocrinopathy - enteropathy, Juberg-Hayward syndrome 10 cases X-linked Juvenile temporal arteritis 20 cases

** Prevalence at birth November 2008 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data 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

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Kabuki syndrome 1.16 LCAT deficiency 30 families Kaler-Garrity-Stern syndrome 2 cases Leber amaurosis, congenital 10 Kallmann syndrome 7.7 Leber hereditary optic neuropathy 6.5 Kallmann syndrome - heart disease 8 cases Legg-Calve-Perthes disease 23 Kaposi’s sarcoma 1.7 Leigh syndrome 2.75** Kapur-Toriello syndrome 2 cases Lemierre syndrome 0.1 Kasabach-Merritt syndrome > 175 cases Lennox-Gastaut syndrome 15 KBG syndrome 45 cases LEOPARD syndrome 200 cases Kearns-Sayre syndrome 2 Leprechaunism 0.1** Kennedy disease 2.8 Leptospirosis 0.24 Keratoconjunctivitis, vernal 21 Lesch-Nyhan syndrome 0.38 Keratoderma - hypotrichosis - 2 cases Leucinosis 15.6 leukonychia Leukaemia, B-cell lymphocytic, 32 Keratoderma palmoplantar - deafness < 10 families chronic Keratoderma palmoplantar - spastic 25 cases Leukaemia, lymphoblastic, acute 6.5 paralysis Leukaemia, myeloid, acute 11.8 Keratosis follicularis - dwarfism - 6 cases cerebral atrophy Leukaemia, myeloid, chronic 6 Keratosis palmaris et plantaris - < 20 cases Leukaemia, promyelocytic, acute 8 clinodactyly Leukocyte adhesion deficiency (LAD) < 350 cases

Keratosis palmoplantaris - < 10 families Leukodystrophy with oligodontia 4 cases esophageal carcinoma Leukoencephalopathy - ataxia - 8 cases Ketoacidosis due to betaketothiolase 60 cases hypodontia - hypomyelination deficiency Leukoencephalopathy - metaphyseal 4 cases KID/HID syndrome > 100 cases chondrodysplasia Kimura disease 200 cases Leukoencephalopathy - palmoplantar 4 cases Klippel-Feil syndrome 2 keratoderma Leukoencephalopathy with bilateral 29 cases Kniest-like dysplasia, lethal form 2 cases anterior temporal lobe cysts Kozlowski-Brown-Hardwick syndrome 2 cases Leukoencephalopathy with brain 39 cases Krabbe disease 0.75** stem, spinal cord involvement - lactate elevation Kudo-Tamura-Fuse syndrome 2 cases Lewis-Pashayan syndrome 3 cases Kumar-Levick syndrome 1 family Lewis-Sumner syndrome 0.9 Lacrimo-auriculo-dento-digital 20 cases Lhermitte-Duclos disease 220 cases syndrome Lichstenstein syndrome 2 cases Lafora disease < 0.1 Li-Fraumeni syndrome 400 families Lambert-Eaton myasthenic syndrome 1 Ligneous conjunctivitis 1.1 Laminopathy, type Decaudain- 9 cases Limb-mammary syndrome 27 cases Vigouroux Lipoamide dehydrogenase deficiency 20 cases Laminopathy-related congenital 15 cases muscular dystrophy Lipodystrophy - mental retardation - 3 cases deafness Langerhans cell histiocytosis 2 Lipodystrophy, acquired generalized 80 cases Larsen syndrome 100 cases Lipodystrophy, Berardinelli type 0.25 Larsen-like syndrome, lethal form < 10 cases Lipodystrophy, familial partial, 10 cases Laryngeal abductor paralysis - < 20 cases associated with PPARG mutations mental retardation Lipodystrophy, familial partial, due 1 family Laryngo-tracheo-oesophageal cleft 1.5 to AKT2 mutations Lateral body wall complex 2** Lipodystrophy, familial partial, 300 cases Lathosterolosis < 5 cases Dunnigan type

** Prevalence at birth

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Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Lipodystrophy, familial partial, < 20 cases Malignant hyperthermia - 4 cases Köbberling type arthrogryposis - torticollis Lipodystrophy, partial acquired 250 cases Malonic aciduria 17 cases Lipoid proteinosis > 280 cases Mandibulofacial dysostosis, X-linked 7 cases Lipomatosis, pancreatic - duodenal 1 case Mantle cell lymphoma 3.9 stenosis Marden-Walker syndrome 30 cases Lissencephaly - immunodeficiency 1 case Marfan syndrome 30 Lissencephaly, type 2 0.12 Marie Unna congenital hypotrichosis 12 families Lissencephaly, type III - familial 5 cases Marinesco-Sjogren syndrome 200 cases foetal akinesia sequence Marshall’s syndrome with periodic 30 cases Lissencephaly, type III - metacarpal 2 cases fever bone dysplasia Marshall-Smith syndrome 33 cases Lobar emphysema, congenital 4.5 Martinez-Frias syndrome 11 cases Long QT syndrome, familial 25 MASA syndrome 3.5 Lopez-Hernandez syndrome 11 cases Mastocytosis, cutaneous 0.75 Low birth weight - dwarfism - 2 cases dysgammaglobulinemia Mastocytosis, systemic 0.33 Lowe syndrome 0.19 Maternal hyperphenylalaninemia 1.25 Lumbosacral vertebrae, posterior 3 cases Matthew-Wood syndrome 5 cases fusion of - blepharoptosis Mayer-Rokitansky-Küster-Hauser 9 Lung cancer, small cell 10 syndrome Lung fibrosis - immunodeficiency - 2 cases Mazabraud syndrome 54 cases gonadal dysgenesis McLeod neuroacanthocytosis 150 cases Lupus erythematosus, bullous 70 cases syndrome systemic Lupus erythematosus, cutaneous 50 Meckel syndrome 4** Meconium aspiration syndrome 2.44 Lymphangioleiomyomatosis 0.1 Median cleft of the upper lip - > 10 cases Lymphoedema - atrial septal 3 cases corpus callosum lipoma - cutaneous defects - facial changes polyps Lymphoedema - cerebral 5 cases arteriovenous anomaly Medullary cystic kidney disease, 0.11 autosomal dominant, with or Lymphoedema, congenital 8.8 without hyperuricemia Macrocephaly - Cutis Marmorata 40 cases Medullary cystic kidney disease, 1.05 Telangiectatica Congenita autosomal recessive Macrocephaly - immune deficiency - 2 cases Megacalycosis, congenital > 50 cases anemia Megacystis microcolon - intestinal 89 cases Macrocephaly - short stature - 2 cases hypoperistalsis - hydronephrosis paraplegia Megalencephaly - polymicrogyria - 6 cases Macrogyria pseudobulbar palsy 4 cases post-axial polydactyly - hydrocephalus Macrophagic myofasciitis 1 MEHMO syndrome 7 cases Macrostomia - preauricular tags - 9 cases external ophthalmoplegia MEHMO syndrome 7 cases Macular degeneration, juvenile - 7 families Melanoma, familial 46.8 hypotrichosis MELAS syndrome 16 Madras motor neuron disease 154 cases Melorheostosis 300 cases Malabsorptive diarrhoea due to 3 cases Mendelian susceptibility to atypical 0.059 paucity of enteroendocrine cells, mycobacteria congenital Meniere disease 42.5 Malakoplasia 500 cases Menkes syndrome 0.7 Malaria 3 Mental retardation - dysmorphism - 4 cases Malignant hyperthermia 33 hypogonadism - diabetes mellitus

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Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Mental retardation - hypoplastic 3 cases Mental retardation, X-linked, Pai 1 family corpus callosum - preauricular tag type Mental retardation - progressive 1 family Mental retardation, X-linked, 1 family spasticity, X-linked recessive - macrocephaly - ciliary dysfunction Mental retardation - sparse hair - 6 cases brachydactyly Mental retardation, X-linked, Reish 2 cases type Mental retardation, X-linked - 2 cases acromegaly - hyperactivity Mental retardation, X-linked, 4 cases Schimke type Mental retardation, X-linked - 5 cases choreoathetosis - abnormal Mental retardation, X-linked, 4 cases behaviour Seemanova type Mental retardation, X-linked - 5 cases Mental retardation, X-linked, severe, 7 cases cubitus valgus - dysmorphism Gustavson type Mental retardation, X-linked - Dandy- 16 cases Mental retardation, X-linked, Shashi 9 cases Walker malformation - basal ganglia type disease - Seizures Mental retardation, X-linked, 3 cases Mental retardation, X-linked - 8 cases Shrimpton type dysmorphism - cerebral atrophy Mental retardation, X-linked, Siderius 4 cases Mental retardation, X-linked - 2 cases type epilepsy - progressive joint Mental retardation, X-linked, Snyder 11 cases contractures - dysmorphism type Mental retardation, X-linked - 3 cases Mental retardation, X-linked, South 16 cases hypogammaglobulinemia - African type progressive neurological deterioration Mental retardation, X-linked, 4 cases Stevenson type Mental retardation, X-linked - 4 cases hypogonadism - ichthyosis - Mental retardation, X-linked, Stocco 4 cases obesity - short stature Dos Santos type Mental retardation, X-linked - 10 cases Mental retardation, X-linked, Stoll 4 cases hypotonia - facial dysmorphism - type aggressive behaviour Mental retardation, X-linked, 10 cases Mental retardation, X-linked - 12 cases syndromic 7 macrocephaly - macro-orchidism Mental retardation, X-linked, < 10 families Mental retardation, X-linked - 2 cases syndromic, due to JARID1C mutation plagiocephaly Mental retardation, X-linked, Vitale 8 cases Mental retardation, X-linked - 3 cases type precocious puberty - obesity Mental retardation, X-linked, Wilson 3 cases Mental retardation, X-linked - 6 cases type psychosis - macroorchidism Mental retardation, X-linked, with 3 families Mental retardation, X-linked - 4 cases isolated growth hormone deficiency seizures - psoriasis Mental retardation, X-linked, with 17 cases Mental retardation, X-linked - 1 family seizures, short stature and midface Spastic paraplegia with iron deposits hypoplasia

Mental retardation, X-linked, Abidi 8 cases Mental retardation, X-linked, Wittwer 3 cases type type Mental retardation, X-linked, 6 cases Mental retardation, X-linked, Zorick 6 cases Armfield type type

Mental retardation, X-linked, Cabezas 1 family MERRF syndrome 0.9 type Mesoaxial synostotic syndactyly with 2 families Mental retardation, X-linked, 2 cases phalangeal reduction Cantagrel type Mesomelic dysplasia - skin dimples 2 cases Mental retardation, X-linked, Lubs 5 cases Metachromatic leukodystrophy 0.16 type Metaphyseal acroscyphodysplasia 4 cases Mental retardation, X-linked, Miles- 4 cases Carpenter type Metaphyseal anadysplasia < 20 cases

** Prevalence at birth

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Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Metaphyseal chondrodysplasia, 16 cases Midface retraction syndrome, 34 cases Jansen type Schinzel-Giedion type Metatropic dwarfism 80 cases Miller-Dieker syndrome 0.3 Methimazole embryofetopathy 40 cases Mirhosseini-Holmes-Walton syndrome < 15 cases Methylcobalamin deficiency type 27 cases Mitochondrial diseases of nuclear 9 cbl E origin Methylcobalamin deficiency, cbl G 33 cases Mitochondrial encephalomyopathy 2 cases type aminoacidopathy Methylmalonic acidemia - 300 cases Mitochondrial myopathy with 7 cases homocystinuria sideroblastic anaemia Methylmalonic aciduria - 2 cases Mitral regurgitation - deafness - 3 cases microcephaly - cataract skeletal anomalies Methylmalonicacidemia - 300 cases Moebius syndrome 300 cases homocystinuria, type cbl C Mohr-Tranebjaerg syndrome 46 cases Methylmalonicacidemia - 5 cases Mononen-Karnes-Senac syndrome 5 cases homocystinuria, type cbl D Monosomy 18p < 200 cases Methylmalonicaciduria - 9 cases homocystinuria, type cbl F Monosomy 22q11 20 Mevalonicaciduria 30 cases Monosomy 22q13 > 200 cases Michels syndrome 7 cases Monosomy 5p 4.6 Micro syndrome 8 cases Monosomy 9q22.3 2 cases Microbrachycephaly - ptosis - cleft 2 cases Moore-Federman syndrome 6 cases lip Mosaic variegated aneuploidy 29 cases Microcephalic osteodysplastic 4 cases syndrome dysplasia, Saul-Wilson type Mowat-Wilson syndrome < 200 cases Microcephaly - brachydactyly - 3 cases kyphoscoliosis Moya-Moya disease 3.16 Microcephaly - cardiomyopathy 3 cases Mucocutaneous venous 40 malformations Microcephaly - cleft palate 3 cases Mucolipidosis type 2 0.15** Microcephaly - digital anomalies - 2 cases intellectual deficit Mucolipidosis type 4 > 100 cases Microcephaly - glomerulonephritis - 2 cases Mucopolysaccharidosis type 1 1.3 marfanoid habitus Mucopolysaccharidosis type 2 0.6 Microcephaly - intellectual deficit - 3 cases Mucopolysaccharidosis type 3 1.1 phalangeal and neurological anomalies Mucopolysaccharidosis type 4 0.4 Microcephaly - micropenis - 4 cases Mucopolysaccharidosis type 6 0.16** convulsions Mucopolysaccharidosis type 7 < 40 cases Microcephaly - seizures - mental 2 cases Mucosulfatidosis 50 cases retardation - heart disease Muenke syndrome 1.8** Microcytic anaemia with liver iron 3 cases overload Muir-Torre syndrome 205 cases Microdontia - type I microtia - 9 cases MULIBREY nanism 115 cases deafness Mullerian derivatives - 3 cases Microgastria - limb reduction defect 16 cases lymphangiectasia - polydactyly Microlissencephaly - micromelia 2 cases Multicentric reticulohistiocytosis < 200 cases Microphthalmia - brain atrophy 3 cases Multifocal motor neuropathy with 1.5 conduction block Microscopic polyangiitis 7.5 Multiple endocrine neoplasia type 1 11 Microtia 15 Multiple endocrine neoplasia, type 2 3.3 Microtia - eye coloboma - 1 family imperforation of the nasolacrimal Multiple fibrofolliculoma, familial 7 cases duct Multiple pterygium syndrome, 4 cases Midas syndrome < 50 cases autosomal dominant

** Prevalence at birth November 2008 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data 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

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Multiple pterygium syndrome, lethal 200 cases Myopathy, reducing body 4 families form Myopathy, X-linked, with excessive 15 families Multiple sclerosis - ichthyosis - 2 cases autophagy factor VIII deficiency N syndrome 3 cases Multiple system atrophy 4.6 N-acetyl-alpha-D-galactosaminidase 12 cases MURCS association 11.25 deficiency Muscular atrophy - ataxia - retinitis 10 cases Naegeli-Franceschetti-Jadassohn 0.035 pigmentosa - diabetes mellitus syndrome Muscular dystrophy congenital, with 0.03 Nail patella-like - renal disease 3 cases integrin deficiency Nail-patella syndrome 2 Muscular dystrophy limb-girdle 0.8 Nance-Horan syndrome 50 families Muscular dystrophy, congenital, non 0.15 Nanism due to growth hormone 3 cases merosin negative qualitative anomaly Muscular dystrophy, congenital, 0.3 Narcolepsy-cataplexy 49 type 1A NARP syndrome 8.5 Muscular dystrophy, Duchenne and 5 Becker types Nasopalpebral lipoma - coloboma - < 30 cases telecanthus Muscular dystrophy, Fukuyama type 0.54 Necrotizing encephalopathy, acute, 11 cases Muscular dystrophy, limb girdle, 14 cases autosomal dominant autosomal recessive, type 2G Nemaline myopathy 1 Muscular dystrophy, limb girdle, > 40 families autosomal recessive, type 2I Neonatal ichthyosis - sclerosing < 10 cases cholangitis Muscular dystrophy, limb-girdle, 1 family autosomal dominant, type 1A Nephroblastoma 10.1 Muscular dystrophy, limb-girdle, 5 families Nephronophtisis familial, adult 2 cases autosomal dominant, type 1D form - spastic quadriparesia Muscular dystrophy, limb-girdle, 5 families Nephropathy - deafness - 5 cases autosomal dominant, type 1E hyperparathyroidism Muscular dystrophy, limb-girdle, 1 family Nephrosis - deafness - urinary tract - 5 cases autosomal dominant, type 1F digital malformations Muscular dystrophy, limb-girdle, 1 family Nephrotic syndrome, idiopathic, 18 autosomal dominant, type 1G steroid-sensitive Muscular dystrophy, tibial 6 Netherton disease 1.35 Muscular dystrophy, Ullrich type, < 100 cases Neu-Laxova syndrome 60 cases congenital Neuroaxonal dystrophy - renal 3 cases Myasthenia gravis 8.5 tubular acidosis Myasthenic syndromes, congenital 0.75 Neuroblastoma 10 Myelodysplastic syndromes 25 Neurodegeneration due to 3- 4 cases hydroxyisobutyryl-CoA hydrolase Myelofibrosis with myeloid 10 deficiency metaplasia Myeloma, multiple 14.25 Neurodegeneration due to 3- 2 cases hydroxyisobutyryl-CoA hydrolase Myhre syndrome 16 cases deficiency

Myoclonic epilepsy of infancy 106 cases Neurodegenerative syndrome, X- 7 cases Myoclonus - cerebellar ataxia - 4 cases linked, Bertini type deafness Neurodegenerative syndrome, X- 10 cases Myoclonus hereditary - progressive < 10 cases linked, Hamel type distal muscular atrophy Neuroectodermal syndrome, Johnson < 30 cases Myoneurogastrointestinal 87 cases type encephalopathy syndrome Neuroectodermal-endocrine 4 cases Myopathy due to calsequestrin and 4 cases syndrome SERCA1 protein overload Neurofibromatosis type 1 25 Myopathy, distal inflammatory, of 10 cases the upper limbs, asymmetric Neurofibromatosis type 2 0.5

** Prevalence at birth

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Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Neurometabolic disorder due to < 30 cases Oculodentoosseous dysplasia 5 cases serine deficiency recessive Neuropathy, giant axonal 20 families Oculo-digito-esophageal-duodenal < 50 cases syndrome (ODED) Neuropathy, hereditary, with liability 9 to pressure palsies Oculogastrointestinal muscular 1 family dystrophy Neuropathy, sensory and autonomic , 35 cases hereditary, type 2 Oculoosteocutaneous syndrome 3 cases Neuropathy, sensory and autonomic, 1 family Oculo-oto-facial dysplasia 4 cases hereditary, with deafness and global Oculo-palato-cerebral syndrome 5 cases delay Oculopharyngeal muscular dystrophy 1 Neuropathy, sensory and autonomic, 1 family hereditary, with deafness, X-linked Oculotrichodysplasia 2 cases Neutropenia cyclic 0.1 Odontomicronychial dysplasia 5 cases Neutropenia severe, congenital 0.4** Odonto-onycho-dermal dysplasia < 15 cases Neutropenia, severe congenital, 7 cases Odontotrichomelic syndrome 4 cases X-linked Odonto-tricho-ungual-digito-palmarn 21 cases Nevo syndrome 10 cases syndrome Nevus of ota - retinitis pigmentosa 1 case Okamoto syndrome 2 cases Niemann-Pick disease 2.5** Oligocone trichromacy 14 cases Niemann-Pick disease, type A 0.25** Olmsted syndrome 32 cases Niemann-Pick disease, type B 0.75** Omodysplasia 30 cases Niemann-Pick disease, type C 0.85 Omphalocele 12 Nijmegen breakage syndrome 1** Omphalocele-cleft palate syndrome, 3 cases lethal Nodular regenerative hyperplasia of 3 the liver Ondine syndrome 2.25 Onycho-tricho-dysplasia - 5 cases Non-distal trisomy 10p 60 cases neutropenia Non-distal trisomy 12p 2** Ophthalmo acromelic syndrome 30 cases Non-distal trisomy 8q > 30 cases Opitz BBB/G syndrome 3 Non-Hodgkin malignant lymphoma 36 Opsismodysplasia 25 cases Norrie disease 300 cases Optic atrophy 6 North Carolina macular dystrophy 2 families Optic atrophy and cataract, 14 cases autosomal dominant Obesity - colitis - hypothyroidism - 2 cases Oral-facial-digital syndrome 1.2 cardiac hypertrophy - developmental syndrome, type 1 delay Oral-facial-digital syndrome, type 10 1 case Obesity due to congenital leptin < 30 cases deficiency Oral-facial-digital syndrome, type 3 3 cases Obesity due to prohormone 2 cases Oral-facial-digital syndrome, type 4 16 cases convertase-I deficiency Oral-facial-digital syndrome, type 5 4 cases Obesity due to pro-opiomelanocortin 7 cases Oral-facial-digital syndrome, type 6 29 cases deficiency Oral-facial-digital syndrome, type 8 2 families Ochoa syndrome > 100 cases Orbital leiomyoma 16 cases Ocular albinism, X-linked recessive 2 Ornithine carbamoyltransferase 1 Ocular motor apraxia Cogan type 50 cases deficiency Oculocerebrocutaneous syndrome 36 cases Orotic aciduria hereditary < 20 cases Oculocerebrofacial syndrome, 9 cases Ossification anomalies - psychomotor 2 cases Kaufman type development delay Oculocutaneous albinism 7.15 Osteochondritis dissecans 35 Oculodental syndrome, Rutherfurd 1 family Osteochondrodysplatic nanism - 2 cases type deafness - retinitis pigmentosa Oculodentodigital dysplasia 243 cases Osteocraniostenosis 12 cases

** Prevalence at birth November 2008 Orphanet Report Series - Prevalence of rare diseases: Bibliographic data 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

Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Osteodysplasty, Melnick-Needles type > 50 cases Papulosis, malignant atrophic > 200 cases Osteogenesis imperfecta 6.5 Paraneoplastic pemphigus > 60 cases Osteogenesis imperfecta - 2 cases Paraplegia - brachydactyly - cone- 5 cases retinopathy - seizures - intellectual shaped epiphysis deficit Paraplegia - mental retardation - 4 cases Osteogenesis imperfecta, 3 cases hyperkeratosis congenital - microcephaly - cataracts PARC syndrome 2 cases Osteopathia striata - cranial sclerosis 100 cases Parietal foramina 5 Osteopetrosis, autosomal dominant, 33 cases Parkinson disease, genetic types 15 type 1 Parkinsonism, young adult onset 37.5 Osteopetrosis, intermediate form 50 cases Parkinson’s disease dementia, 41 Osteopetrosis, malignant, autosomal 0.75** familial recessive Paroxysmal extreme pain disorder 4 families Osteopoikilosis - short stature - 4 cases intellectual deficit Paroxysmal nocturnal 0.55 haemoglobinuria Osteoporosis - pseudoglioma 0.05 Parsonage-Turner syndrome 3.3 Osteoporosis-oculocutaneous- 3 cases hypopigmentation syndrome Partington syndrome 2 families Osteosarcoma 5 Pearson syndrome 60 cases Osteosclerosis - ichthyosis - 3 cases Pelizaeus-Merzbacher disease 0.25 premature ovarian failure PELVIS syndrome 11 cases Osteosclerotic bone dysplasia, lethal 8 families Pemphigus vulgaris 3.8 Otodental syndrome 9 families Pendred syndrome 5.5 Otopalatodigital syndrome 30 cases Pericarditis - arthropathy - < 30 families Overhydrated hereditary 20 families camptodactyly stomatocytosis Perinatal-lethal Gaucher disease 0.01 P2Y12, deficiency of 5 cases Perioral myoclonia with absences < 10 cases Pachydermoperiostosis 204 cases Peritoneal leiomyomatosis, 100 cases Pachyonychia congenita 230 cases disseminated Pacman dysplasia < 10 cases Perlman syndrome 30 cases Paget disease juvenile type 50 cases Perrault syndrome 34 cases Pallister-Hall syndrome 100 cases Persistent hyperinsulinemic 2 hypoglycemia of infancy Palmoplantar hypokeratosis, 17 cases circumscribed Persistent Mullerian duct syndrome < 200 cases Peters-plus syndrome 50 cases Palmoplantar keratoderma - 4 cases amyotrophy Peutz-Jeghers syndrome 2.2

Palmoplantar keratoderma - XX 5 cases Pfeiffer syndrome 0.38 sex reversal - predisposition to PHACE syndrome 100 cases squamous cell carcinoma Phaeochromocytoma and 10 Palmoplantar keratoderma, diffuse, 2.5 paraganglioma, secreting Norrbotten dominant type Phenylketonuria 4 Palmoplantar porokeratosis of < 10 cases Phosphoenolpyruvate carboxykinase < 10 cases Mantoux (PEPCK) deficiency Pancreas agenesis 8 cases Phosphoglycerate kinase 1 deficiency 23 cases Pancreatic hypoplasia - diabetes - < 10 cases Phosphoribosylpyrophosphate < 30 families heart disease synthetase superactivity Pancreatitis, acute, recurrent 10 Phytosterolemia 40 cases Pancreatitis, hereditary 0.125 PIBIDS syndrome 20 cases Pancreatoblastoma 60 cases Piebaldism 0.25 Panniculitis, cytophagic histiocytic < 100 cases Pierre Robin sequence - faciodigital 2 cases Papillon-Lefevre syndrome 0.25 anomaly

** Prevalence at birth

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Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Pierre Robin sequence, isolated 8.75 Progressive bulbar paralysis of < 40 cases childhood Pierson syndrome 22 cases Progressive neurodegeneration - 2 cases Pili torti - onychodysplasia 1 family joint laxity - cataract Pilodental dysplasia - refractive 2 cases Progressive vertebral fusion, non- 10 cases errors infectious, syndromic form Pityriasis rubra pilaris 48 cases Progressive vertebral fusion, non- 10 cases Plummer-Vinson syndrome 25 cases infectious, syndromic form Poikiloderma of Kindler 100 cases Prolidase deficiency 50 cases Poland anomaly 2 Propionic acidemia 3.75 Pollitt syndrome 10 cases Proteus syndrome 200 cases Polyarteritis nodosa 3.07 Protoporphyria, erythropoietic 0.9 Polyarthritis, juvenile, rheumatoid 8 Proximal myotonic myopathy 1 factor-negative Pseudoachondroplasia 3 Polyarthritis, juvenile, rheumatoid 4.2 Pseudoarthrosis of clavicle, > 200 cases factor-positive congenital Polycystic kidney disease, autosomal 30 cases Pseudodiastrophic dysplasia 10 cases dominant, type 1, with tuberous sclerosis Pseudohypoaldosteronism, type 1 70 cases Polycystic kidney disease, autosomal 6.5 Pseudoprogeria syndrome 2 cases recessive Pseudoxanthoma elasticum 2.5 Polycystic lipomembranous 0.15 Pseudo-Zellweger syndrome < 10 cases osteodysplasia - sclerosing leukoencephalopathy Psychomotor retardation due to 3 cases S-adenosylhomocysteine hydrolase Polycystic ovaries - urethral 33 cases deficiency sphincter dysfunction Pterygium colli - intellectual 2 cases Polycythemia vera 25 deficit - digital anomalies

Polydactyly, preaxial 25 Pterygium popliteal syndrome, 0.3 autosomal dominant Polymorphic catecholergic 10 ventricular tachycardia Pterygium syndrome, antecubital 11 cases

Polymyositis 14.8 Ptosis - strabismus - ectopic pupils 1 family Polysyndactyly - cardiac 6 cases Ptosis - strabismus - rectus 2 cases malformation abdominis diastasis Pontocerebellar hypoplasia type 1 6 families Pulmonary alveolar proteinosis 0.1 Pontocerebellar hypoplasia type 2 < 30 cases Pulmonary arterial hypertension 1.5 Porphyria, acute hepatic 8 Pulmonary fibrosis, idiopathic 27 Porphyria, chronic hepatic 1.5 Pulmonary haemosiderosis, primary 250 cases Porphyria, congenital erythropoietic > 200 cases Pulmonary lymphangiectasia, > 100 cases congenital Posterior column ataxia - retinitis 13 cases pigmentosa Pulmonary valve stenosis, congenital 7.2 Post-transplant lymphoproliferative 26.2 Pure autonomic failure 0.1 disease Pyle disease < 30 cases Potocki-Shaffer syndrome 23 cases Pyogenic arthritis - pyoderma 34 cases Prader-Willi syndrome 10.7 gangrenosum - acne Primary biliary cirrhosis 13.5 Qazi-Markouizos syndrome 3 cases Primary ciliary dyskinesia 5 Radiation proctitis 35 Primary lateral sclerosis 1.5 Radio-ulnar synostosis - < 20 cases amegakaryocytic thrombocytopaenia Primary sclerosing cholangitis 11 Rambaud-Galian syndrome 3 cases Progeria 0.25** RAPADILINO syndrome < 20 cases Progeria - short stature - pigmented < 10 cases nevi Rapid-onset dystonia-parkinsonism 3 families

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Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Rapp-Hodgkin syndrome 72 cases Rudiger syndrome 2 cases Rasmussen subacute encephalitis > 100 cases Sacral hemangiomas - multiple 5 cases Recurrent infections - short stature - 4 cases congenital abnormalities hypopigmentation - coarse face Saethre-Chotzen syndrome 3 Refsum disease 0.1 Sakati-Nyhan syndrome < 5 cases Refsum disease, infantile form 0.005 Sandhoff disease 0.75 Regional odontodysplasia 139 cases Sarcoidosis 15 Relapsing polychondritis 3.5 Sarcosinemia 2 Renal agenesis, bilateral 17 Renal-hepatic-pancreatic dysplasia - 10 cases Say-Barber-Miller syndrome 2 cases Dandy-Walker cysts Scalp defects - postaxial polydactyly 2 cases Rendu-Osler-Weber disease 3.5 Scalp-ear-nipple syndrome 30 cases Renpenning syndrome 10 families SCARF syndrome 2 cases Restrictive cardiomyopathy, 2.5 idiopathic or familial Schinzel syndrome < 10 families Retinal arteries, tortuosity of 100 cases Schizencephaly 1.54 Retinal degeneration - 7 cases Schizophrenia - intellectual deficit - 1 family nanophtalmos - glaucoma deafness - retinitis Retinitis pigmentosa 27.5 Schnitzler syndrome 50 cases

Retinitis pigmentosa - intellectual 2 families Schopf-Schulz-Passarge syndrome 19 cases deficit - deafness - hypogenitalism Schwartz-Jampel syndrome 100 cases Retinoblastoma 5.4 Scleroderma 42 Retinohepatoendocrinologic 7 cases syndrome Sebastian syndrome < 10 families Seckel syndrome 100 cases Retinoschisis, X-linked 4.5 Segmental odontomaxillary dysplasia 32 cases Rett syndrome 4.15 Seizures - intellectual deficit due to 3 cases Rhabdoid tumour 500 cases hydroxylysinuria Rheumatic fever 5 Senior-Loken syndrome 0.1 Rhombencephalosynapsis 50 cases Sensenbrenner syndrome 15 cases Rickettsialpox > 800 cases Sensorineural hearing loss, early 3 cases Rieger syndrome 0.5 greying, and essential tremor Ring chromosome 1 34 cases SERKAL syndrome 3 cases

Ring chromosome 10 < 20 cases Serpentine fibula - polycystic 6 cases kidneys Ring chromosome 14 50 cases Ring chromosome 17 14 cases Severe achondroplasia - 4 cases developmental delay - acanthosis Ring chromosome 18 70 cases nigricans Ring chromosome 20 > 50 cases Severe combined immunodeficiency 0.22 Ring dermoid of cornea < 30 cases due to adenosine deaminase deficiency Roberts syndrome 100 cases Robinow syndrome > 120 cases Severe combined immunodeficiency 0.35 T- B- Robinow-like syndrome 2 cases Severe combined immunodeficiency 1.5 Rolled and spiral hairs - 4 cases T- B+, X-linked palmoplantar keratoderma Sex development disorder - 3 cases Rothmund-Thomson syndrome 300 cases intellectual deficit Rubella panencephalitis > 20 cases Sex development disorder, 46,XX - 2 cases Rubella syndrome, congenital 1** skeletal anomalies Rubinstein-Taybi syndrome 1 Sezary’s syndrome 0.18

** Prevalence at birth

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Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Short stature - mental retardation - 3 cases Spinal muscular atrophy, proximal 3 eye anomalies - cleft/lip palate Spinal muscular atrophy, proximal, 0.26 Short stature - pituitary and 1 family type 1 cerebellar defects - small sella turcica Spinal muscular atrophy, proximal, 2.6 type 2 Short stature - webbed neck - heart 4 cases disease Spinal muscular atrophy, proximal, 2.6 type 3 Short stature due to growth hormone 0.2 resistance Spinal muscular atrophy, proximal, 0.32 type 4 Short stature, Brussels type 2 cases SHORT syndrome 30 cases Spinocerebellar ataxia, infantile 21 cases onset Shprintzen-Goldberg syndrome < 50 cases Split hand - split foot 1.1 Shwachman-Diamond syndrome 200 cases Split hand - split foot - deafness 22 cases Sialidosis type 1 0.02** Split hand - urinary anomalies - 3 cases Sialidosis, type 2 0.02** spina bifida Sickle cell anaemia 11 Spondyloenchondrodysplasia 36 cases Sideroblastic anaemia, X-linked < 200 cases Spondylometaphyseal dysplasia 0.34 Siegler-Brewer-Carey syndrome 2 cases Spondylometaphyseal dysplasia - 8 cases Silent sinus syndrome 98 cases cone-rod dystrophy Sillence syndrome 5 cases Spondylometaphyseal dysplasia with 4 cases combined immunodeficiency Silver-Russell dwarfism 400 cases Spontaneous periodic hypothermia < 30 cases Simpson-Golabi-Behmel syndrome > 100 cases Sporotrichosis 55 cases Simpson-Golabi-Behmel syndrome, 4 cases type 2 Squamous cell carcinoma of head 46 and neck Singleton-Merten dysplasia < 10 cases Stargardt disease 11.25 Sirenomelia 1** Steinert myotonic dystrophy 4.5 Sjögren-Larsson syndrome 0.4 Sternal cleft < 2 Skeletal dysplasia - intellectual 2 families deficit Stern-Lubinsky-Durrie syndrome 7 cases Small vessel disease of the brain, 2 cases Steroid dehydrogenase deficiency - 1 family not NOTCH3-related dental anomalies Smith-Lemli-Opitz syndrome 6.5 Stickler syndrome 13.5 Smith-Magenis syndrome 4 Stiff-man syndrome 0.1 Soft tissue sarcomas 13 Still’s disease, adult onset 1.23 Sotos syndrome 7** Stimmler syndrome 2 cases Sparse hair - short stature - skin 4 cases Stoll-Alembik-Finck syndrome 2 cases anomalies Stoll-Alembik-Finck syndrome 1 case Spastic paraplegia - glaucoma - 2 families Stormorken-Sjaastad-Langslet 6 cases intellectual deficit syndrome Spastic paraplegia - nephritis - 4 cases Stromal keratitis 16 deafness Subcorneal pustular dermatosis 200 cases Spastic paraplegia - precocious 2 cases puberty Succinic acidemia 50 cases Spastic paraplegia, familial 5 Succinyl-CoA acetoacetate 10 cases transferase deficiency Spastic quadriplegia - retinitis 2 cases pigmentosa - mental retardation Sucrase-isomaltase deficiency, 20 congenital Spasticity - mental retardation - 6 cases epilepsy, X-linked Summitt syndrome 3 cases Superficial pemphigus 1.2 Spherocytosis hereditary 20 Supranuclear palsy, progressive 3.7 Spinal muscular atrophy - Dandy- 2 cases Walker complex - cataracts Supravalvar aortic stenosis 12.5

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Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Susac syndrome < 100 cases Torticollis - keloids - 7 cases cryptorchidism - renal dysplasia Sympathetic ophthalmia 0.6 Symphalangism with multiple 6 cases Townes-Brocks syndrome 0.42 anomalies of hands and feet Tracheal agenesis 1** Symphalangism, distal < 5 families Tracheobronchomegaly < 100 cases Syndactyly, Cenani-Lenz type < 30 cases Transmissible spongiform 0.3 Syndactyly, type 1 25 encephalopathies Syndactyly, type 4 4 cases Transposition of the great arteries 32.5 Syngnathia multiple anomalies 2 cases Treacher-Collins syndrome 6 Synostoses, multiple 20 families Treft-Sanborn-Carey syndrome 23 cases Synspondylism 24 cases Trichodental syndrome < 5 families Syringomyelia 8.4 Tricho-dento-osseous syndrome > 30 cases Takayasu arteritis 0.45 Trichodysplasia - amelogenesis 1 family imperfecta Talo-patello-scaphoid osteolysis 2 cases Trichomegaly - cataract - 2 cases Tangier disease > 70 cases spherocytosis, hereditary Taurodontia - absent teeth - sparse < 15 cases hair Trichomegaly - retina pigmentary 11 cases degeneration - dwarfism Tay-Sachs disease 0.3** Tricho-odonto-onychial dysplasia 4 cases Teebi-Shaltout syndrome 2 cases Tricho-retino-dento-digital syndrome 9 cases Terminal osseous dysplasia - 18 cases pigmentary defects Trichorhinophalangeal syndrome, > 100 cases type 1 and 3 Tetraamelia - pulmonary hypoplasia 5 families Tetralogy of Fallot 45 Tricuspid atresia 5 Thalamic calcifications, symmetrical 29 cases Trigonocephaly - bifid nose - acral 2 cases anomalies Thalidomide embryopathy 5000 cases Trigonocephaly - broad thumbs 2 cases Thanatophoric dwarfism 3.5** Trigonocephaly - short stature - 3 cases Thiamine-responsive megaloblastic 30 families developmental delay anaemia syndrome Triose phosphate-isomerase 30 cases Thomsen and Becker disease 5 deficiency Thrombocythemia, essential 27.5 Triphalangeal thumbs - 4 families Thrombocytopenia - Robin sequence 2 cases brachyectrodactyly

Thrombocytopenic purpura, 25 Triple A syndrome 100 cases autoimmune Triple H (HHH) syndrome 50 cases Thumb absent - short stature - 3 cases Triplo-X syndrome 42.5 immune deficiency Trisomy 13 13** Thumb stiffness - brachydactyly - 6 cases Trisomy 18 9** mental retardation Tritanopia 4.8 Thymic-renal-anal-lung dysplasia 3 cases True hermaphrodism > 500 cases Thyrocerebrorenal syndrome 2 cases Tuberculosis 20 Thyroid carcinoma, anaplastic 0.13 Tuberous sclerosis 8.8 Thyroid carcinoma, medullary 7 Tubular renal disease - 2 cases Thyrotoxic periodic paralysis 2 cardiomyopathy Tibial aplasia - ectrodactyly 0.1 Tufted angioma > 200 cases Tibial hemimelia 0.1 Turner syndrome 20 Tietz syndrome 1 family Tyrosinemia type 1 0.05 Tomé-Brunet-Fardeau syndrome 4 cases Tyrosinemia, type 2 < 100 cases Toriello-Carey syndrome 60 cases Uhl anomaly 84 cases Toriello-Lacassie-Droste syndrome 10 cases Ulbright-Hodes syndrome 3 cases

** Prevalence at birth

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Diseases name Estimated number of Diseases name Estimated number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Ulnar/fibula ray defect - 1 family WHIM syndrome 40 cases brachydactyly Whipple disease 1000 cases Umbilical cord ulceration - intestinal 15 cases Wieacker-Wolff syndrome 6 cases atresia Wiedemann-Rautenstrauch syndrome 25 cases Unverricht-Lundborg disease 0.2 Williams syndrome 13.3 Upington disease 1 family Wilson disease 5.84 Usher syndrome 3.5 Wilson-Turner syndrome > 14 cases VACTERL with hydrocephalus < 10 families Winchester disease 12 cases Van den Bosch syndrome 1 family Wiskott-Aldrich syndrome 0.15 Van Der Woude syndrome 2 Wolcott-Rallison syndrome 17 cases Vasculitis 6.3 Wolf-Hirschhorn syndrome 2** VATER association 23 Wolfram syndrome 0.57 Visceral neuropathy - brain 2 cases anomalies - facial dysmorphism - Wolman disease 0.28** developmental delay Woods-Black-Norbury syndrome 5 cases Vitamin B12 responsive 60 cases Woolly hair - hypotrichosis - everted 1 family methylmalonic acidemia, type cbl A lower lip - outstanding ears Von Hippel-Lindau disease 0.2 Woolly hair - palmoplantar < 20 cases Von Willebrand disease 12.5 keratoderma - dilated cardiomyopathy Von Willebrand syndrome, acquired 300 cases Wrinkly skin syndrome < 30 cases Vulvovaginal gingival syndrome 127 cases Xanthinuria 150 cases W syndrome 6 cases Xanthomatosis cerebrotendinous 0.13 Waardenburg syndrome 2.4 Xeroderma - talipes - enamel defects 2 cases Waardenburg-Shah syndrome 50 cases Xeroderma pigmentosum 0.5 Waldenström macroglobulinemia 2.6 XK aprosencephaly < 10 cases Walker-Warburg syndrome 1.65** X-linked dominant chondrodysplasia 0.5 Weaver syndrome 30 cases punctata Weaver-Williams syndrome 2 cases X-linked lymphoproliferative disease 0.1 Wegener granulomatosis 6.6 Zadik-Barak-Levin syndrome 1 case Weill-Marchesani syndrome 128 cases Zellweger syndrome 1.1 Wells syndrome 80 cases Zellweger-like syndrome, without 2 cases Werner syndrome 0.45 peroxisomal anomalies West syndrome 3.7** Zollinger-Ellison syndrome 5.3 Western equine encephalitis > 600 cases Zunich-Kaye syndrome 6 cases