Prevalence of rare diseases : A bibliographic survey Orphanet February 2008 Rep rt Method Series By alphabetical list of diseases

By decreasing prevalence

By reported number of published cases

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. 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 Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf  Prevalences by alphabetical list of diseases

Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families 2,4-dienoyl-CoA reductase deficiency 1 case Acrofacial dysostosis, Nager type 90 cases 2,8 dihydroxyadenine urolithiasis 1,7 Acrofacial dysostosis, palagonia type 4 cases 3C syndrome 25 cases Acrofacial dysostosis, Preis type 1 case 3-hydroxy 3-methylglutaryl-CoA 6 cases Acro-fronto-facio-nasal dysostosis 5 cases (HMG) synthase Acromegaloid facial appearance < 20 cases 3-hydroxyacyl-CoA dehydrogenase, 1 syndrome long chain, deficiency of Acromegaloid facies - hypertrichosis < 20 cases 3M syndrome 40 cases Acromegaly 5 3-methylcrotonylglycinuria 2,25 Acromegaly - cutis verticis gyrata - 16 cases 3-methylglutaconic aciduria, type 1 20 cases corneal leukoma 3-methylglutaconic aciduria, type 3 10 Acromelanosis < 10 cases 46 xx gonadal dysgenesis epibulbar 1 case Acromesomelic dysplasia brahimi 3 cases dermoid bacha type 46,XX disorders of sex development - 2 cases Acromesomelic dysplasia Hunter- 10 cases skeletal anomalies Thompson type 4-hydroxybutyricaciduria 350 cases Acromesomelic dysplasia, Maroteaux 50 cases 5-oxoprolinase deficiency 8 cases type 6-pyruvoyl-tetrahydropterin synthase, 248 cases Acromicric dysplasia < 40 cases deficiency Acroosteolysis dominant type 50 cases 6q terminal deletion 19 cases Acro-pectoral syndrome 22 cases Aarskog-Scott syndrome > 200 cases Acro-pectoro-renal field defect 12 cases Aase-Smith syndrome < 10 cases Acropectorovertebral dysplasia < 30 cases Ablepharon macrostomia syndrome 15 cases Acrorenal syndrome 20 cases Abruzzo-Erickson syndrome 4 cases Acro-renal-mandibular syndrome 7 cases Acalvaria < 1** Acro-renal-ocular syndrome < 20 Families Acanthamoeba keratitis 1 Acute interstitial pneumonia 3,8 Acatalasemia 3,1 Acute lymphoblastic leukemia 7,5 Aceruloplasminemia 0,05 Acute non lymphoblastic leukemia 7 Achalasia - microcephaly 5 cases Acute promyelocytic leukemia 8 Acheiropodia < 10 Families Acute Respiratory Distress Syndrome, 30 Achondrogenesis > 100 cases Adult Achondroplasia 4,5 Acyl-CoA dehydrogenase, medium 15 Ackerman syndrome 8 cases chain, deficiency of Acquired generalized lipodystrophy 80 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 deaminase 200 cases Acrofacial dysostosis autosomal 2 cases deficiency recessive Adenylosuccinate lyase deficiency 50 cases Acrofacial dysostosis catania form 6 cases Adrenal hyperplasia, congenital 10 Acrofacial dysostosis postaxial, 1 case atypical Adrenocortical carcinoma 1 Acrofacial dysostosis Rodriguez type < 10 cases Adrenoleukodystrophy, X-linked 5 ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf  Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Adult Onset Still’s disease 1,23 Amoebiasis due to free-living 1,75 amoebae ADULT syndrome 14 cases Amyotrophic lateral sclerosis 6 Agammaglobulinemia - microcephaly - 3 cases craniosynostosis - severe dermatitis Anaemia, sideroblastic, X-linked - 5 Families ataxia Agammaglobulinemia X-linked 0,45 Androgen insensitivity syndrome 13 Agenesis of the corpus callosum - 2 cases mental retardation - coloboma - Anencephaly 3,2** micrognathia Angelman syndrome 6,5 Aglossia adactylia < 50 cases Angel-shaped phalango-epiphyseal 15 cases Agnathia holoprosencephaly situs 30 cases dysplasia inversus Angioedema 1 Agonadism - dextrocardia - 6 cases Angioma neurocutaneous, hereditary < 10 Families diaphragmatic hernia Angioma serpiginosum, familial 2 Families Aicardi syndrome 500 cases Angio-osteohypertrophic syndrome 1000 cases Aicardi-Goutieres syndrome 100 cases Aniridia 1,75 Alagille syndrome 1,4 Aniridia - cerebellar ataxia - mental > 10 Families Alar cartilages hypoplasia - 2 cases deficiency coloboma - telecanthus Aniridia absent patella 3 cases Albers-Schonberg disease 1 Aniridia ptosis mental retardation 3 cases Albinism ocular - late onset 7 cases obesity familial type sensorineural deafness Aniridia renal agenesis psychomotor 2 cases Albinism-deafness syndrome 1 Family retardation Albright hereditary osteodystrophy 0,72 Aniridia-mental retardation syndrome 2 cases Albright like syndrome 10 cases Anisakiasis 3,8 Alexander disease 300 cases Ankyloblepharon - ectodermal 8 Families Alkaptonuria 0,3 defects - cleft lip palate Alopecia - congenita keratosis 1 Family Ankyloblepharon filiforme - 2 Families palmoplantaris imperforate anus Alopecia - contractures - dwarfism - 5 cases Ankylosing vertebral hyperostosis 8 cases mental retardation with tylosis Alopecia - hypogonadism - 2 cases Anonychia - onychodystrophy with 11 cases extrapyramidal disorder hypoplasia or absence of distal phalanges Alopecia- epilepsy - pyorrhea - mental 12 cases subnormality Anonychia microcephaly 5 cases Alopecia totalis 10,5 Anonychia with flexural pigmentation 3 cases Alpers syndrome 0,025 Anophthalmia - hypothalamo- 30 cases pituitary insufficiency Alpha thalassemia- mental 168 cases retardation, X-linked Anophthalmia - megalocornea - 3 cases cardiopathy - skeletal anomalies Alpha-mannosidosis 0,1 Anophthalmia - Microphthalmia, 14 Alpha-sarcoglycanopathy 0,57 isolated Alport syndrome 2 Anophthalmia - short stature - 1 case Alström syndrome 300 cases obesity 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 Amaurosis congenita of Leber 2,5 Anorectal malformation 24 Ambras syndrome 10 cases Antisynthetase syndrome 1,5 Amelia, autosomal recessive 3 cases Antley-Bixler syndrome 34 cases Amelo-cerebro-hypohidrotic syndrome 19 cases Antley-Bixler-like syndrome - 16 cases Aminopterin embryofetopathy 17 cases ambiguous genitalia - disordered Amniotic bands 4** steroidogenesis

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf  Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Aortic aneurysm syndrome, Loeys- 10 Families Atelosteogenesis III 12 cases Dietz type Athabaskan brainstem dysgenesis 10 cases Aortic arch anomaly peculiar facies 4 cases syndrome mental retardation Atherosclerosis- deafness - diabetes - 2 cases Aortic arch interruption 0,3** epilepsy - nephropathy Aortic dilatation- joint hypermobility- 22 cases Atkin-Flaitz syndrome 14 cases arterial tortuosity Atransferrinemia 9 cases Aorto-ventricular tunnel 130 cases Atresia of small intestine 20 Apert syndrome 1,25 Atrial septal defect atrioventricular 11 cases Aphalangia - syndactyly - 1 Family conduction microcephaly Atrial tachyarrhythmia with short pr 12 cases Aphalangy - hemivertebrae - 3 cases interval urogenital-intestinal dysgenesis Atrioventricular canal, complete 15** Aplasia cutis - myopia 4 cases Atrioventricular canal, partial 20 Aplasia cutis congenita - intestinal 3 cases Atypical coarctation of aorta 0,17** lymphangiectasia Aughton syndrome 2 cases Aplasia cutis congenita of limbs 6 cases recessive Auricular abnormalities - cleft lip 2 cases with or without cleft palate - ocular Aplastic anaemia 0,4 abnormalities Arachnodactyly - mental retardation - 3 cases Auriculoocular anomalies - cleft lip 2 cases dysmorphism Aurocephalosyndactyly 5 cases Arachnodactyly ossification abnormal 5 cases mental retardation Autism 45 AREDYLD syndrome 3 cases Autoimmune lymphoproliferative 100 cases syndrome Argininemia 31 cases Autoimmune polyendocrinopathy, 4 Arhinia choanal atresia 4 cases type 1 microphthalmia Axenfeld-Rieger anomaly - 3 cases Aromatase deficiency 13 cases hydrocephaly - skeletal abnormalities Arrhinia 20 cases Babesiosis 40 cases Arrhythmogenic right ventricular 43,5 Bacterial toxic-shock syndrome 3 dysplasia Bamforth syndrome 5 cases Arterial dissection - lentiginosis 4 cases Bangstad syndrome 2 cases Arterial tortuosity < 40 cases Arthritis-related enthesitis 5,7 Banki syndrome 1 Family Arthrogryposis - hyperkeratosis, lethal 2 cases Barber-Say syndrome 10 cases form Bardet-Biedl syndrome 0,8 Arthrogryposis - renal dysfunction - < 150 cases Bartsocas-Papas syndrome 24 cases cholestasis Bartter syndrome 0,12 Arthrogryposis multiplex congenita 30 B-cell chronic lymphocytic leukemia 32 Arthrogryposis multiplex congenita - 10 cases whistling face Beckwith-Wiedemann syndrome 7,3 Ascher syndrome 50 cases Beemer-Ertbruggen syndrome 2 cases Astley-Kendall dysplasia < 10 cases Behcet disease 2,5 Ataxia - apraxia - mental retardation, 9 cases Bencze syndrome 2 Families X-linked Benign exophthalmos syndrome 4 cases Ataxia - deafness - optic atrophy, 12 cases lethal Benign paroxysmal torticolis of 50 cases infancy Ataxia telangiectasia 1 Bernard-Soulier syndrome 100 cases Ataxia, autosomal recessive, Beauce 57 cases type Best disease 4,4 Ataxia-deafness-retardation syndrome 8 cases Beta-mannosidosis 14 cases Atelosteogenesis I 12 cases Beta-sarcoglycanopathy 0,57 Atelosteogenesis II 25 cases Beta-ureidopropionase deficiency 5 cases ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf  Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Bethlem myopathy 100 cases Bronchopulmonary dysplasia 13 Bickel-Fanconi glycogenosis 112 cases Brown-Vialetto-van Laere syndrome < 100 cases Biliary atresia 5,6 Budd-Chiari syndrome 1,5 Biliary tract malformation - renal 6 cases Buerger’s disease 12,5 failure Bullous dystrophy, macular type 2 Families Birt-Hogg-Dube syndrome > 60 Families Bullous ichthyosiform erythroderma 0,4 Blackfan-Diamond disease 0,32 congenita Blaichman syndrome 1 case Bullous pemphigoid 2,5 Blepharo-facio-skeletal syndrome 2 cases Bullous systemic lupus erythematosus 70 cases Blepharonasofacial malformation 2 Families Buttiens-Fryns syndrome 3 cases syndrome CADASIL 500 cases Blepharophimosis - ptosis - 6 cases Calpainopathy 3,8 esotropia - syndactyly - short stature Calvarial doughnut lesions - bone 20 cases Blepharoptosis - myopia - ectopia 3 cases fragility lentis CAMFAK syndrome 3 Families Bloom syndrome > 100 cases CAMOS syndrome 5 cases Blue rubber bleb nevus > 200 cases Campomelia Cumming type 8 cases Bone dysplasia azouz type 1 case Campomelic dysplasia 0,35 Bone dysplasia corpus callosum 1 case agenesis Camptobrachydactyly 1 Family Bone dysplasia lethal holmgren type 4 cases Camptodactyly - fibrous tissue 3 cases hyperplasia - skeletal dysplasia Bone fragility, craniosynostosis, 4 cases proptosis, hydrocephalus Camptodactyly - tall stature - 30 cases scoliosis - hearing loss Bone tumor 10 Camptodactyly - taurinuria 4 Families Bonnemann-Meinecke-Reich syndrome 4 cases Camptodactyly syndrome guadalajara 8 cases Book syndrome 25 cases type 1 Boomerang dysplasia 10 cases Camptodactyly syndrome, Guadalajara 2 cases BOR syndrome 2,5 type 2 Bosley-Salih-Alorainy syndrome 9 cases Camurati engelmann disease 200 cases Botulism 0,05 Cantrell pentalogy 0,55** Boutonneuse fever 17 Capillary leak syndrome 57 cases Bouwes Bavinck syndrome 2 cases Carbamoylphosphate synthetase 0,7 deficiency Bowen-Conradi syndrome 44 cases Carcinoma of the gallbladder 6,5 Brachydactyly - arterial hypertension > 10 Families Cardiac conduction disease, dilated 10 cases Brachydactyly long thumb type 4 cases cardiomyopathy and brachydactyly Brachymorphism - onychodysplasia - 9 cases Cardiogenital syndrome 7 cases dysphalangism Cardiomyopathy - cataract - hip spine 9 cases Brachytelephalangy - dysmorphism - 2 cases disease Kallmann syndrome Cardiomyopathy - renal anomalies 2 cases Braddock syndrome 2 cases Cardiomyopathy, familial dilated 17,5 Bradyopsia 5 cases Carey fineman ziter syndrome < 20 cases Brain malformation - congenital heart 2 cases disease - postaxial polydactyly Carney complex 160 cases Branchial arch syndrome, X-linked 7 cases Carnitine palmitoyl transferase 1 35 cases deficiency Branchiogenic deafness syndrome 5 cases Carnitine palmitoyl transferase 2 > 100 cases Branchio-oculo-facial syndrome < 50 cases deficiency Branchio-skeleto-genital syndrome 3 cases Carnitine-acylcarnitine translocase 30 cases Breast cancer, familial 17 deficiency Carnosinemia 30 cases Bronchopneumopathy, chronic, due to < 20 cases TAP deficiency Caroli’s disease < 250 cases

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf  Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Carpenter syndrome 40 cases Cerebellar ataxia, autosomal 1 Family recessive - saccadic intrusion Carpo tarsal osteochondromatosis < 10 cases Cerebral arteriovenous fistula 6 Carpo tarsal osteolysis recessive < 10 cases Cerebral gigantism - jaw cysts < 10 cases Castleman disease 400 cases Cerebro-costo-mandibular syndrome 60 cases Cataract - hypertrichosis - intellectual 1 case deficit Cerebro-oculo-nasal syndrome 10 cases Cataract - microphthalmia - septal 2 cases Cerebroretinal vasculopathy 3 Families defect Ceroid lipofuscinosis, neuronal 4 Cataract - nephropathy - 2 cases Cervical hypertrichosis - peripheral 3 cases encephalopathy neuropathy Cataract- ataxia - deafness 2 cases CHAND syndrome > 10 cases Cataract cardiomyopathy 30 cases Chaotic atrial tachycardia 100 cases Cataract deafness hypogonadism 3 cases Char syndrome 10 cases Cataract mental retardation 10 cases Charcot-Marie-Tooth disease - 10 cases hypogonadism nephropathy Cataract-glaucoma 3 Families Charcot-Marie-Tooth disease 32,5 Cataract-microcornea syndrome 8 Families CHARGE association 0,14 Catel-Manzke syndrome 27 cases Chediak-Higashi syndrome > 10 cases Cat-eye syndrome 1,35 CHILD syndrome 30 cases Cat-scratch disease 6,6 Choanal atresia - deafness - cardiac 5 cases Caudal dysgenesis familial type 4 cases defects - dysmorphism CDG syndrome 1,5** Cholangiocarcinoma 10 CDG syndrome type Ia 300 cases Cholestasis - lymphoedema, syndrome 50 cases CDG syndrome type Ib 20 cases Cholestasis pigmentary retinopathy 4 cases cleft palate CDG syndrome type Ic > 30 cases Cholesteryl ester storage disease < 50 cases CDG syndrome type Id 5 cases Chondrodysplasia - disorder of sex 2 cases CDG syndrome type Ie 7 cases development CDG syndrome type If 4 cases Chondrodysplasia lethal recessive 4 cases CDG syndrome type Ig 6 cases Chondrodysplasia punctata, rhizomelic 1 CDG syndrome type Ih 5 cases type CDG syndrome type Ii 1 case Chondrodysplasia situs inversus 1 case CDG syndrome type IIa 4 cases imperforate anus polydactyly CDG syndrome type IIb 1 case Chondrodysplasia, Blomstrand type 13 cases CDG syndrome type IId 1 case Chordoma 0,05 CDG syndrome type IIe 2 cases Chorioretinal atrophy, progressive 2 Families bifocal CDG syndrome type Ij 1 case Choroidal atrophy alopecia 2 cases CDG syndrome type Ik 4 cases Choroidal dystrophy, central areolar 3,33 CDG syndrome type IL 2 cases Choroideremia 2 CDG syndrome, type IIh 2 cases Choroideremia deafness obesity 4 cases CEDNIK syndrome 7 cases Choroido cerebral calcification 10 cases Celiac disease epilepsy occipital 170 cases syndrome infantile form calcifications Christ-Siemens-Touraine syndrome 0,35 Central neurocytoma > 100 cases Chromosome Y deletion 42 Cerebellar ataxia - areflexia - pes 2 Families cavus - optic atrophy - sensorineural Chronic hiccup 1 hearing loss Chronic inflammatory demyelinating 4,4 Cerebellar ataxia, autosomal dominant 2,15 polyneuropathy Cerebellar ataxia, autosomal recessive 7 Chronic recurrent multifocal > 260 cases osteomyelitis, juvenile Cerebellar ataxia, autosomal 3 Families recessive - blindness - deafness Churg-Strauss syndrome 1 ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf  Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Chylomicron retention disease 40 cases Corneal dystrophy - perceptive < 10 cases deafness CINCA syndrome 100 cases Corneal dystrophy ichthyosis 1 case Cleft lip and palate malrotation 4 cases microcephaly mental retardation cardiopathy Corneal-cerebellar syndrome 2 cases Cleft lip palate - mental retardation - 2 cases corneal opacities Cornelia de Lange syndrome 5,25 Cleft lip retinopathy 2 cases Coronary artery disease - 1 Family hyperlipidemia - hypertension - Cleft palate - cardiac defect - genital 5 cases diabetes - osteoporosis anomalies - ectrodactyly Corpus callosum agenesis 19 Cleft palate lateral synechia syndrome 7 cases neuronopathy Cleft palate short stature vertebral 2 cases Corpus callosum dysgenesis, X-linked 11 cases anomalies recessive Cleft palate stapes fixation 2 cases Corpus callosum, agenesis - cataract - 8 cases oligodontia immunodeficiency Cleido rhizomelic syndrome 2 cases Cortical blindness - mental 3 cases Clouston syndrome 1 retardation - polydactyly Cloverleaf skull syndrome 150 cases Corticobasal degeneration 4 COACH syndrome 8 cases Corticosteroid-sensitive aseptic 49 cases Coats disease 2 abscesses Cobb syndrome 35 cases Costello syndrome 200 cases Cockayne syndrome 200 cases Costocoracoid ligament congenitally 1 Family short Coffin-Lowry syndrome 0,55 Cowden syndrome 0,45 Coffin-Siris syndrome 40 cases Coxoauricular syndrome 4 cases Cogan syndrome 200 cases Coxo-podo-patellar syndrome 47 cases Cohen syndrome 100 cases Cranio fronto nasal dysplasia poland 3 cases Collagenous colitis 10,5 anomaly Coloboma of macula - brachydactyly 12 cases Cranio osteoarthropathy 4 cases type B Craniodiaphyseal dysplasia > 20 cases Coloboma uveal with cleft lip palate 12 cases and mental retardation Craniodigital syndrome mental 4 cases retardation Coloboma, ocular 1 Craniofacial conodysplasia 1 Family Colobomatous microphthalmia heart 10 cases disease hearing loss Craniofacial dysmorphism - 3 cases coloboma - corpus callosum agenesis Cone rod dystrophy 2,5 Craniofacial dyssynostosis 0,05 Cone rod dystrophy amelogenesis 29 cases imperfecta Craniofacial-deafness-hand syndrome 3 cases Congenital alopecia, X linked 1 Family Craniofaciocardioskeletal syndrome 4 cases Congenital anosmia, isolated < 15 cases Craniofrontonasal dysplasia, Teebi 20 cases type Congenital brain dysgenesis due to < 30 cases glutamine synthetase deficiency Craniolenticulosutural dysplasia 21 cases Congenital bronchobiliary fistula 23 cases Craniometaphyseal dysplasia 70 cases Congenital cataracts - facial 100 cases Craniosynostosis - dysmorphism - 5 cases dysmorphism - neuropathy brachydactyly Congenital ichthyosis microcephalus 2 cases Craniosynostosis - intracranial 3 cases quadriplegia calcifications Congenital lobar emphysema 4,5 Craniosynostosis dandy walker 4 cases hydrocephalus Congenital rubella syndrome 1** Craniosynostosis fibular aplasia 2 cases Contractures ectodermal dysplasia 2 cases cleft lip palate Craniosynostosis radial aplasia type 2 cases imaizumi Cooper-Jabs syndrome 2 cases Craniosynostosis, Boston type 19 cases Corneal anesthesia deafness mental 2 cases retardation Craniosynostosis, Philadelphia type 1 Family ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf  Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Craniotubular syndrome 2 cases Deafness-mental retardation, Martin- 3 cases Probst type Creutzfeldt-Jakob disease 0,1 Deafness-mental retardation, Martin- 3 cases Crigler-Najjar syndrome < 0,1 Probst type Crisponi syndrome 18 cases Deafness-tubular acidosis-anaemia 2 cases Criss-cross heart 0,8 Defective expression of HLA class 2 100 cases Crouzon disease 2 Dehydratase deficiency 21 cases Cryptomicrotia - brachydactyly - 2 cases Deletion 2q24 23 cases excess fingertip arch Delta-sarcoglycanopathy 0,57 Cryptosporidiosis 34 DEND syndrome 14 cases Curry-Jones syndrome 5 cases Dentatorubral pallidoluysian atrophy < 0,3 Cutaneous albinism, ermine 3 cases phenotype Dentinogenesis imperfecta - short 2 cases stature - hearing loss - mental Cutaneous mastocytosis 0,75 retardation Cutaneous neuroendocrine carcinoma 0,5 Denys-Drash syndrome 150 cases Cutaneous photosensitivity colitis 3 cases Depigmentation of the iris, acute, 5 cases lethal bilateral Cutis gyrata acanthosis nigricans 6 cases Dermatitis herpetiformis 20,2 craniosynostosis Dermato-cardio-skeletal syndrome 2 cases Cutis laxa > 100 cases Borrone type Cutis marmorata telangiectatica 300 cases Dermatofibrosarcoma protuberans 10 congenita Dermatoleukodystrophy 2 cases Cutis verticis gyrata - mental deficit 1,02 Dermatomyositis 14,8 Cyprus facial neuromusculoskeletal 1 Family syndrome Dermatoosteolysis Kirghizian type 5 cases Cystathioninuria 7 Dermo-odonto dysplasia 14 cases Cystic fibrosis 12 Dermopathy restrictive lethal 30 cases Cystic hamartoma of lung and kidney < 5 cases Desbuquois syndrome > 40 cases Desmosterolosis 2 cases Cystic hygroma lethal - cleft palate 2 cases Developmental delay due to 2- < 30 cases Cystinosis 0,5 methylbutyryl-CoA dehydrogenase Cystinuria 14 deficiency Cystoid macular dystrophy 6 Families Developmental dysphasia familial 6 Families Dacryocystitis osteopoikilosis 5 cases Developmental malformations - 2 cases deafness - dystonia Dahlberg - Borer - Newcomer, 2 cases Diabetes insipidus, nephrogenic 0,5 syndrome Diabetes mellitus, neonatal 0,2 Dandy walker macrocephaly 2 cases Diabetes mellitus, permanent 4 cases Dandy walker malformation postaxial 2 cases neonatal - pancreatic and cerebellar polydactyly agenesis Darier disease 1,5 Diabetes, neonatal - congenital 2 cases Deaf blind hypopigmentation 2 cases hypothyroidism - congenital glaucoma - hepatic fibrosis - Deafness - lymphoedema - leukemia < 10 cases polycystic kidneys Deafness - opticoacoustic nerve 3 cases Diaphanospondylodysostosis < 10 cases atrophy - dementia Diaphragmatic defect - limb 4 cases Deafness - peripheral neuropathy - 4 cases deficiency - skull defect arterial disease Diaphragmatic hernia - exomphalos - 13 cases Deafness - vitiligo - achalasia 2 cases corpus callosum agenesis Deafness skeletal dysplasia lip 8 cases Diaphragmatic hernia, congenital 15 granuloma Diastrophic dwarfism 3,5 Deafness, enamel hypoplasia, nail 6 cases Diffuse leiomyomatosis - Alport 0,1 defects syndrome X-linked Deafness-infertility syndrome 3 Families Diffuse neonatal haemangiomatosis < 70 cases ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf  Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Digitorenocerebral syndrome < 10 cases Ectodermal dysplasia berlin type 4 cases Digitotalar dysmorphism 6 Ectodermal dysplasia mental 1 case retardation syndactyly Dihydropteridine reductase deficiency 134 cases Ectodermal dysplasia, anhidrotic, with 2 cases Dihydropyrimidinuria 7 cases immunodeficiency, osteopetrosis, and Dincsoy-Salih-Patel syndrome 2 cases lymphoedema Disorder of sex development - mental 3 cases Ectodermal dysplasia, hypohidrotic - 3 cases retardation hypothyroidism - ciliary dyskinesia Distal monosomy 5q 10 cases Ectodermal dysplasia, hypohidrotic, 40 cases Distal monosomy 8p 20 cases autosomal dominant Distal myopathy with posterior leg 12 cases ‘Ectodermal dysplasia, ‘’pure’’ hair-nail < 20 cases and anterior upper limb involvement type’ Distal myopathy with vocal cord 12 cases Ectodermic dysplasia hypothyroidism 3 cases weakness cleft Distal myopathy, Nonaka type 0,1 Ectopia lentis chorioretinal dystrophy 4 cases myopia Distal myopathy, Welander type 10 Ectopia lentis isolated 6,4 Distal myopathy, with early 24 cases respiratory muscle involvement Ectrodactyly - ectodermal dysplasia 5 cases without clefting DOOR syndrome < 50 cases EEM syndrome 7 Families Dopamine beta-hydroxylase deficiency 12 cases Ehlers-Danlos syndrome type 10 1 Family Dopa-responsive dystonia 0,3 Ehlers-Danlos syndrome type 3 12,5 Double outlet left ventricle 32 cases Ehlers-Danlos syndrome type 4 1 Double uterus-hemivagina-renal < 60 cases agenesis Ehlers-Danlos syndrome type 7C 7 cases Duane anomaly - myopathy - scoliosis 2 cases Ehlers-Danlos syndrome, classic type 3,5 Duane syndrome 10 Ehlers-Danlos syndrome, type 5 2 Families Dubowitz syndrome 150 cases Ehrlichiosis < 50 cases Duker-Weiss-Siber syndrome 4 cases Eiken syndrome 6 cases Duodenal atresia 8,55 Elejalde syndrome 30 cases Dyggve-Melchior-Clausen disease 60 cases Ellis Van Creveld syndrome 150 cases Dyschondrosteosis - nephritis 1 Family Emery-Dreifuss muscular dystrophy 0,3 Dyserythropoietic anaemia, congenital 1 Encephalo cranio cutaneous 45 cases lipomatosis Dyskeratosis congenita 0,1 Encephalopathy due to < 30 cases Dysmorphism - short stature - 2 cases hydroxykynureninuria deafness - pseudohermaphroditism Enchondromatosis 600 cases Earlobes, thickened - conductive 2 Families Endocrine tumour 1 deafness Eng strom syndrome 2 cases Early infantile epileptic 88 cases encephalopathy Eosinophilic fasciitis 200 cases Early myoclonic encephalopathy 30 cases Eosinophilic gastroenteritis 280 cases Early onset torsion dystonia 0,4 Eosinophilic pneumonia, acute > 100 cases idiopathic Ear-patella-short stature syndrome 42 cases Epidermal nevus syndrome > 400 cases Ebstein anomaly 0,75 Epidermolysis bullosa simplex - limb < 20 cases Ectodermal dysplasia - absent < 30 cases girdle muscular dystrophy dermatoglyphs Epidermolysis bullosa, acquired 100 cases Ectodermal dysplasia - blindness 2 cases Epidermolysis bullosa, dystrophic 0,27 Ectodermal dysplasia - skin fragility 10 cases syndrome Epidermolysis bullosa, epidermolytic 2,5 Ectodermal dysplasia alopecia preaxial 1 case Epidermolysis bullosa, junctional 0,06 polydactyly Epilepsy microcephaly skeletal 2 cases Ectodermal dysplasia arthrogryposis 1 case dysplasia diabetes mellitus Epilepsy telangiectasia 6 cases ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf  Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Epilepsy, pyridoxin-dependent 0,15 Fibrinogen deficiency, congenital 0,15 Epiphyseal dysplasia multiple 5 Fibrochondrogenesis 11 cases Episodic ataxia, type 3 1 Family Fibrodysplasia ossificans progressiva 0,08 Episodic ataxia, type 4 2 Families Fibromatosis, gingival - progressive 2 Families deafness Erdheim-Chester disease 178 cases Fibrous dysplasia of bone < 0,05 Erythermalgia, primary 30 Families Fibular aplasia - ectrodactyly < 50 cases Erythroderma lethal congenital 17 cases Fibular dimelia - diplopodia 11 cases Erythrokeratodermia ataxia 25 cases Fine-Lubinsky syndrome 5 cases Erythrokeratodermia variabilis, > 200 cases Mendes da Costa type Fingerprints absence - congenital 14 cases milia Esophageal atresia 25 Flynn aird syndrome 10 cases Esophageal carcinoma 8 Focal dermal hypoplasia 300 cases Esthesioneuroblastoma < 1000 cases Focal dystonia 11,7 Evans syndrome 0,1 Focal facial dermal dysplasia < 10 Families Ewing sarcoma 0,1 Focal myositis 50 cases Exostoses, multiple 4 Folate malabsorption, hereditary 17 cases Eyebrow duplication syndactyly 3 cases Follicular lymphoma 36 Fabry disease 1,75 Foveal hypoplasia presenile cataract 11 cases Facial dysmorphism macrocephaly 3 cases myopia dandy walker Fragile X syndrome 14,25 Facial onset sensory and motor 4 cases Fraser syndrome 150 cases neuronopathy Freeman-Sheldon syndrome 100 cases Faciocardiomelic dysplasia lethal 3 cases Fried syndrome 1 Family Facioscapulohumeral muscular 7 Friedreich ataxia 2,5 dystrophy Frontometaphyseal dysplasia < 30 cases Factor II deficiency 10 Frontotemporal dementia 3 Factor V deficiency 0,1 Fronto-temporal dementia and 50 cases Factor VII deficiency 0,25 Parkinsonism linked to chromosome Factor XI deficiency, congenital 0,1 17 (FTDP-17) Fructose intolerance 5 Factor XIII deficiency, congenital 0,04 Fructose-1,6-bisphosphatase 2,5 Fahr syndrome < 20 Families deficiency Familial adenomatous polyposis 5,25 Fryns syndrome 7** Familial cold urticaria 0,1 Fucosidosis 100 cases Familial dysautonomia 550 cases Fuhrmann syndrome 11 cases Familial hematuria, autosomal 8 cases Fumaric aciduria > 20 cases dominant - retinal arteriolar Fuqua-Berkovitz syndrome 2 cases tortuosity - contractures Galactosemia 6,6 Familial platelet syndrome with < 20 Families predisposition to acute myelogenous Galloway-Mowat syndrome 40 cases leukemia Gamma aminobutyric acid 2 cases Familial platelet syndrome with 13 Families transaminase deficiency predisposition to acute myelogenous Gamma-glutamyl transpeptidase 7 cases leukemia deficiency Familial venous malformations 40 Gamma-glutamylcysteine synthetase 9 cases Fanconi anaemia 1 deficiency Fanconi ichthyosis dysmorphism 6 cases Gamma-sarcoglycanopathy 1,96 Femur-fibula-ulna complex 1,5 GAPO syndrome 27 cases Fetal cytomegalovirus syndrome 40 Gardner-Morrison-Abbott syndrome 3 cases Fetal methyl mercury syndrome 800 cases Gastric cancer 20 Fetal varicella syndrome > 100 cases Gastrointestinal stromal tumor 1,8 ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 10 Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Gastroschisis 12 Grange syndrome 6 cases Gaucher disease - ophthalmoplegia - < 10 cases Granulomatous arthritis of childhood 40 Families cardiovascular calcification Granulomatous disease, chronic 0,2 Gaucher disease 1 Granulomatous slack skin < 50 cases Gaucher disease type 1 0,94 Gräsbeck-Imerslund disease 300 cases Gaucher disease type 2 0,01 Gray platelet syndrome 20 cases Gaucher disease, type 3 0,05 Great vessels transposition (TGV) 32,5 Geleophysic dwarfism 27 cases Greenberg dysplasia < 10 cases Gelineau disease 49 Greig syndrome 100 cases Genitopatellar syndrome 7 cases Griscelli disease 60 cases German syndrome 5 cases Growth deficiency - brachydactyly - 2 Families Geroderma osteodysplastica 30 cases dysmorphism Giant cell arteritis 8,9 Growth delay - intellectual deficit - 4 cases mandibulofacial dysostosis - Giant pigmented hairy nevus 2 microcephaly - cleft palate Glaucoma - ectopia - 3 cases Growth retardation - microcephaly - 4 cases microspherophakia - stiff joints - digital abnormalities - hypospadias short stature GTP cyclohydrolase I deficiency 17 cases Glaucoma - sleep apnoea 5 cases Guanidinoacetate methyltransferase 9 cases Glioblastoma 11 deficiency Global developmental delay - 3 cases Hair defect photosensitivity mental 3 cases osteopenia - ectodermal defect retardation Glomerulonephritis sparse hair < 10 cases telangiectases Hallermann-Streiff-Francois syndrome < 100 cases Glucocorticoid deficiency, familial 50 cases Harding ataxia 1 Glucose-galactose malabsorption 200 cases Hartnup syndrome 4 Glucosephosphate isomerase 50 cases Heart defects - limb shortening 2 cases deficiency Hec syndrome 2 cases Glutaryl-CoA dehydrogenase deficiency 0,4 Hemimelia 4,15 Glutathione synthetase deficiency 65 cases Hemiplegic migraine, familial 6,5 Glycogen storage disease due to 84 cases LAMP-2 deficiency Hemolytic anaemia, lethal - genital 2 cases anomalies Glycogen storage disease type 2 1,1 Hemophilia 7,7 Glycogen storage disease type 4 0,6 Hemophilia, acquired 0,1 Glycogen storage disease type 7 < 30 cases Hemorrhagic disorders due to < 20 cases Glycogen storage, type 0 16 cases collagen receptors deficiency Goldberg-Shprintzen megacolon 10 cases Hennekam syndrome > 50 cases syndrome Hennekam-Beemer syndrome 2 cases Goldenhar syndrome 3,5 Hepatic venoocclusive disease 11 Goldmann-Favre syndrome < 50 cases Hepatic veno-occlusive disease - < 25 cases Gombo syndrome 4 cases immunodeficiency Gonadal dysgenesis, XX type 12 Hepatitis, chronic autoimmune 0,75 Gonadal dysgenesis, XY type - 2 cases Hereditary inclusion body myopathy - 19 cases associated anomalies joint contractures - ophthalmoplegia Goodman syndrome 3 cases Hereditary sensory and autonomic 35 cases Goodpasture syndrome 0,64 neuropathy, type 2 Gorham-Stout disease 200 cases Hereditary vascular retinopathy 1 Family Gorlin syndrome 1 Hereditary vascular retinopathy 1 Family Gorlin-Chaudhry-Moss, syndrome 4 cases HERNS syndrome 3 Families GRACILE syndrome 2,12** Hersh-Podruch-Weisskopf syndrome 2 cases Graft versus host disease 3,4 Heterotaxia 2,5

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 11 Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Hidrotic ectodermal dysplasia Halal 4 cases Hypogammaglobulinemia due to CD19 4 cases type deficiency Hidrotic ectodermal dysplasia type 6 cases Hypogonadism - retinitis pigmentosa 3 cases Christianson-Fourie Hypokalemic periodic paralysis 1 Hirschsprung disease 20 Hypokeratosis, palmo-plantar, 17 cases Hirschsprung disease - deafness - 2 cases circumscribed polydactyly Hypomagnesemia with hypocalciuria 3 Families Hirschsprung disease - nail 3 cases Hypomagnesemia with normocalciuria 2 cases hypoplasia - dysmorphism Hypomandibular faciocranial 4 cases Histidinemia 4 dysostosis Hodgkin lymphoma 10,5 Hypomyelination - congenital cataract 8 cases Holoprosencephaly 7 Hypomyelination - hypogonadotropic 4 cases Holt-Oram syndrome 1 hypogonadism - hypodontia Homocarnosinosis 4 cases Hypomyelination - hypogonadotropic 4 cases hypogonadism - hypodontia Homocystinuria due to cystathionine 0,4 beta-synthase deficiency Hypoparathyroidism familial isolated < 10 Families Humeroradial synostosis 150 cases Hypoparathyroidism X-linked 2 Families Humeroradioulnar synostosis 30 cases Hypoparathyroidism, deafness and 12 cases renal disease (HDR) Humerospinal dysostosis 5 cases Hypopituitarism - microphthalmia < 10 cases Humeroulnar synostosis 5 cases Hypopituitarism - postaxial 6 cases Huntington disease 6,2 polydactyly Hyaluronidase deficiency 1 case Hypotelorism - cleft palate - 13 cases Hydrocephalus - blue sclerae - 1 Family hypospadias nephropathy Hypothyroidism - dermoid cyst - cleft 1 case Hydrocephalus - costovertebral 8 cases palate dysplasia - Sprengel anomaly Hypothyroidism - dysmorphism - 5 cases Hydrocephaly tall stature joint laxity 2 cases postaxial polydactyly - intellectual Hydrolethalus 5** deficit Hypercoagulability syndrome, due 2 cases Hypothyroidism, congenital 29 to glycosylphosphatidylinositol Hypotrichosis - lymphoedema - 4 cases deficiency telangiectasia Hyperferritinemia, hereditary, with > 64 cases Hypotrichosis simplex 38 cases congenital cataracts Hypotrichosis-mental retardation 2 cases Hyperglycinemia, isolated nonketotic 0,2 lopes type Hyperimmunoglobinemia D with 180 cases IBIDS syndrome 15 cases recurrent fever ICF syndrome 50 cases Hyperkalemic periodic paralysis 0,75 Ichthyosis - hepatosplenomegaly - 2 cases Hyperkeratosis - hyperpigmentation 10 cases cerebellar degeneration syndrome Ichthyosis - male hypogonadism 5 cases Hyperlipidemia type 3 7,8 Ichthyosis - oral and digital 2 cases Hyperlipoproteinemia type 1 0,6 anomalies Hyperoxaluria 0,2 Ichthyosis alopecia eclabion 4 cases Hypertrichosis cubiti - short stature 28 cases ectropion mental retardation Hypertrichosis lanuginosa congenita < 100 cases Ichthyosis bullosa of Siemens < 20 cases Hypertrichosis lanuginosa, acquired 60 cases Ichthyosis congenita biliary atresia 2 cases Hypertrichosis, anterior cervical, < 20 cases Ichthyosis congenita, harlequin type < 100 cases isolated Ichthyosis follicularis - atrichia - 10 cases Hypertrichotic osteochondrodysplasia 18 cases photophobia Hypochondroplasia 3,3 Ichthyosis prematurity syndrome 16 Families Ichthyosis, X-linked 16,6 Hypocomplementaemic < 100 cases leucocytoclasic vasculitis Idiopathic hypersomnia 4

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 12 Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families IMAGe syndrome < 20 cases Kabuki syndrome 1,16 Iminoglycinuria 6,68 Kaler garrity stern syndrome 2 cases Immune dysregulation - 7 Families Kallmann syndrome 7,7 polyendocrinopathy - enteropathy, X Kallmann syndrome - heart disease 8 cases linked Kaposi’s sarcoma 1,7 Immunodeficiency due to interleukin- < 15 cases 1 receptor-associated kinase-4 Kapur-Toriello syndrome 2 cases deficiency Kasabach-Merritt syndrome > 175 cases Immunodeficiency due to selective 100 cases KBG syndrome 45 cases anti-polysaccharide antibody deficiency Kearns-Sayre syndrome 2 Immunodeficiency with natural-killer 4 cases Kennedy disease 2,8 cell deficiency Keratoderma - epithelioma - dental 5 cases Immunodeficiency, common variable 7,5 abnormalities- hypogonadism Inappropriate antidiuretic hormone 2 cases Keratoderma hypotrichosis 2 cases secretion syndrome leukonychia Inclusion body myositis, IBM 0,49 Keratoderma palmoplantar - deafness < 10 Families Incontinentia pigmenti 0,2 Keratoderma palmoplantar - spastic 25 cases paralysis Infant epilepsy with migrant focal 29 cases crisis Keratosis follicularis - dwarfism - 6 cases cerebral atrophy Infantile neuroaxonal dystrophy > 150 cases Keratosis palmoplantaris - esophageal < 10 Families Inflammatory pseudotumor of the 143 cases carcinoma liver Ketoacidosis due to betaketothiolase 60 cases Insomnia, familial fatal 27 cases deficiency Insulin resistance, short fifth 1 Family KID syndrome > 100 cases metacarpals Kimura disease 200 cases Intellectual deficit, severe - epilepsy - 2 cases anal anomalies - distal phalangeal Klippel feil syndrome 2 hypoplasia Kniest-like dysplasia, lethal 2 cases Internal carotid agenesis 100 cases Krabbe disease 0,75** Interstitial granulomatous dermatitis < 20 cases Kudo tamura fuse syndrome 2 cases with arthritis Lacrimo-auriculo-dento-digital 20 cases Iris coloboma with ptosis - 10 cases syndrome intellectual deficit Lafora disease < 0,1 Iris dysplasia - hypertelorism - 2 cases deafness Lambert-Eaton myasthenic syndrome 1 Isotretinoin-like syndrome 6 cases Lamellar ichthyosis > 0,33 Isovaleric acidemia 1 Langerhans cell histiocytosis 2 IVIC syndrome 4 Families Larsen syndrome 100 cases Jackson-Weiss syndrome 2 Families Laryngeal abductor paralysis - mental < 20 cases retardation Jacobsen syndrome 150 cases Laryngo-tracheo-esophageal cleft 1,5 Jeune syndrome 0,2 Lateral body wall complex 2** Job syndrome 250 cases Lathosterolosis < 5 cases Johanson-Blizzard syndrome 23 cases LCAT deficiency 30 Families Johnson neuroectodermal syndrome < 30 cases Leber hereditary optic neuropathy 6,5 Joubert syndrome 0,85 Legg-Calve-Perthes disease 23 Juberg hayward syndrome 10 cases Leigh syndrome 2,75** Juvenile hyaline fibromatosis 50 cases Lennox-Gastaut syndrome 15 Juvenile idiopathic arthritis, 6,3 systemic-onset Lenz-Majewski hyperostotic dwarfism 7 cases Juvenile macular degeneration, 7 Families LEOPARD syndrome > 70 cases hypotrichosis Leprechaunism 0,1** Juvenile temporal arteritis 20 cases Leptospirosis 0,24 ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 13 Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Lesch-Nyhan syndrome 0,38 Macrogyria pseudobulbar palsy 4 cases Lethal osteosclerotic bone dysplasia 8 Families Macrophagic myofasciitis 1 Leucinosis 15,6 Macrostomia - preauricular tags - 9 cases external ophthalmoplegia Leukemia, chronic myeloid 6 Malabsorptive diarrhea due to paucity 3 cases Leukocyte adhesion deficiency (LAD) < 350 cases of enteroendocrine cells, congenital Leukodystrophy with oligodontia 4 cases Malakoplasia 500 cases Leukoencephalopathy - metaphyseal 4 cases Malignant hyperthermia 33 chondrodysplasia Malignant hyperthermia - 4 cases Leukoencephalopathy - palmoplantar 4 cases arthrogryposis - torticollis keratoderma Malonic aciduria 17 cases Lewis-Pashayan syndrome 3 cases Mandibuloacral dysplasia 37 cases Lewis-Sumner syndrome 0,9 Mantle cell lymphoma 3,9 Lhermitte-Duclos disease 220 cases Marden-Walker syndrome 30 cases Lichstenstein syndrome 2 cases Marfan syndrome 30 Li-Fraumeni syndrome 400 Families Marie Unna congenital hypotrichosis 12 Families Ligneous conjunctivitis > 150 cases Marinesco-Sjogren syndrome 200 cases Limb-mammary syndrome 27 cases Marshall’s syndrome with periodic 30 cases Lipoamide dehydrogenase deficiency 20 cases fever Lipodystrophy - mental retardation - 3 cases Marshall-Smith syndrome 33 cases deafness Martinez monasterio pinheiro 1 case Lipodystrophy, Berardinelli type 0,25 syndrome Lipodystrophy, familial partial, 10 cases associated with PPARG mutations MASA syndrome 3,5 Lipodystrophy, familial partial, due to 1 Family Maternal hyperphenylalaninemia 1,25 AKT2 mutations Matthew-Wood syndrome 5 cases Lipodystrophy, familial partial, 300 cases Mayer-Rokitansky-Küster-Hauser 9 Dunnigan type syndrome Lipodystrophy, familial partial, < 20 cases Mazabraud syndrome 54 cases Köbberling type McCune-Albright syndrome 158 cases Lipodystrophy, partial acquired 250 cases Lipoid proteinosis > 280 cases Meckel syndrome 4** Lissencephaly - immunodeficiency 1 case Meconium aspiration syndrome 2,44 Lissencephaly type 2 0,12 Median cleft of the upper lip - corpus > 10 cases callosum lipoma - cutaneous polyps Liver disease - retitinitis pigmentosa - 4 cases polyneuropathy - epilepsy Medullary cystic kidney disease, 0,11 autosomal dominant, with or without Long QT syndrome, familial 25 hyperuricemia Lopez-Hernandez syndrome 11 cases Medullary cystic kidney disease, 1,05 Low birth weight - dwarfism - 2 cases autosomal recessive dysgammaglobulinemia Megacalycosis, congenital > 50 cases Lowe syndrome 0,19 Megacystis microcolon - intestinal 89 cases Lumbosacral vertebrae, posterior 3 cases hypoperistalsis - hydronephrosis fusion of - blepharoptosis Megalencephaly - polymicrogyria - 6 cases Lung cancer, small cell 5 post-axial polydactyly - hydrocephalus Lymphangioleiomyomatosis 0,1 MEHMO syndrome 7 cases Lymphoedema - cerebral 5 cases MEHMO syndrome 7 cases arteriovenous anomaly Melanoma, familial 46,8 Macrocephaly - Cutis Marmorata 40 cases MELAS syndrome 16 Telangiectatica Congenita Melorheostosis 300 cases Macrocephaly - immune deficiency - 2 cases anemia Mendelian susceptibility to atypical 0,059 mycobacteria Macrocephaly - short stature - 2 cases paraplegia Meniere’s disease 42,5 ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 14 Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Menkes syndrome 0,7 Mental retardation, X-linked, 2 cases Cantagrel type Mental retardation - dysmorphism - 4 cases hypogonadism - diabetes mellitus Mental retardation, X-linked, Lubs 5 cases type Mental retardation - hypoplastic 3 cases corpus callosum - preauricular tag Mental retardation, X-linked, Miles- 4 cases Carpenter type Mental retardation - progressive 1 Family spasticity, X-linked Mental retardation, X-linked, Pai type 1 Family Mental retardation sparse hair 6 cases Mental retardation, X-linked, Reish 2 cases brachydactyly type Mental retardation X-linked - 6 cases Mental retardation, X-linked, Schimke 4 cases psychosis - macroorchidism type Mental retardation, X linked - 3 cases Mental retardation, X-linked, 4 cases precocious puberty - obesity Seemanova type Mental retardation, X linked, with 17 cases Mental retardation, X-linked, severe, 7 cases seizures, short stature, and midface Gustavson type hypoplasia Mental retardation, X-linked, Shashi 9 cases Mental retardation, X-linked - 2 cases type acromegaly - hyperactivity Mental retardation, X-linked, 3 cases Mental retardation, X-linked - 5 cases Shrimpton type choreoathesis - abnormal behavior Mental retardation, X-linked, Siderius 4 cases Mental retardation, X-linked - cubitus 5 cases type valgus - dysmorphism Mental retardation, X-linked, Snyder 11 cases Mental retardation, X-linked - Dandy 16 cases type Walker malformation - Basal ganglia Mental retardation, X-linked, South 16 cases disease - Seizures African type Mental retardation, X-linked - 8 cases Mental retardation, X-linked, 4 cases dysmorphism - cerebral atrophy Stevenson type Mental retardation, X-linked - 2 cases Mental retardation, X-linked, Stocco 4 cases epilepsy - progressive joint Dos Santos type contractures - dysmorphism Mental retardation, X-linked, Stoll 4 cases Mental retardation, X-linked - 3 cases type hypogammaglobulinemia - progressive neurological deterioration Mental retardation, X-linked, 10 cases syndromic 7 Mental retardation, X-linked - 4 cases hypogonadism - ichthyosis - obesity - Mental retardation, X-linked, < 10 Families short stature syndromic, due to JARID1C mutation Mental retardation, X-linked - 10 cases Mental retardation, X-linked, Vitale 8 cases hypotonia - facial dysmorphism - type aggressive behavior Mental retardation, X-linked, Wilson 3 cases type Mental retardation, X-linked - 12 cases macrocephaly - macro-orchidism Mental retardation, X-linked, with 3 Families isolated growth hormone deficiency Mental retardation, X-linked - 2 cases plagiocephaly Mental retardation, X-linked, Wittwer 3 cases type Mental retardation, X-linked - 4 cases seizures - psoriasis Mental retardation, X-linked, Zorick 6 cases type Mental retardation, X-linked - Spastic 1 Family paraplegia with iron deposits MERRF syndrome 0,9 Mental retardation, X-linked 1 Family Mesomelic dysplasia skin dimples 2 cases recessive - macrocephaly - ciliary Metachromatic leukodystrophy 0,16 dysfunction Metaphyseal acroscyphodysplasia 4 cases Mental retardation, X-linked, Abidi 8 cases Metaphyseal anadysplasia < 20 cases type Metaphyseal chondrodysplasia, Jansen 16 cases Mental retardation, X-linked, Armfield 6 cases type type Metatropic dwarfism 80 cases Mental retardation, X-linked, Cabezas 1 Family type Methimazole embryofetopathy 40 cases

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 15 Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Methylmalonic acidemia - 300 cases Mucolipidosis type 2 0,15** homocystinuria Mucolipidosis type 4 > 100 cases Methylmalonic aciduria - 2 cases Mucopolysaccharidosis type 1 1,3 microcephaly - cataract Mucopolysaccharidosis type 2 0,6 Mevalonicaciduria 30 cases Mucopolysaccharidosis type 3 1,1 Michels syndrome 7 cases Mucopolysaccharidosis type 4 0,4 Micro syndrome 8 cases Mucopolysaccharidosis type 6 0,16** Microbrachycephaly - ptosis - cleft lip 2 cases Mucopolysaccharidosis type 7 < 40 cases Microcephalic osteodysplastic 4 cases dysplasia, Saul-Wilson type Mucosulfatidosis 50 cases Microcephaly - cleft palate 3 cases Muenke syndrome 1,8** Microcephaly - glomerulonephritis - 2 cases Muir-Torre syndrome 205 cases marfanoid habitus Mullerian derivatives - 3 cases Microcephaly - seizures - mental 2 cases lymphangiectasia - polydactyly retardation - heart disease Multifocal motor neuropathy with 1,5 Microcephaly cardiomyopathy 3 cases conduction block Microcephaly micropenis convulsions 4 cases Multiple endocrine neoplasia type 1 11 Microcytic anaemia - liver iron 3 cases Multiple endocrine neoplasia, type 2 3,3 overload - low ferritinemia Multiple fibrofolliculoma familial 7 cases Microdontia - type I microtia - 9 cases Multiple pterygium syndrome, 4 cases deafness autosomal dominant Microgastria - limb reduction defect 16 cases Multiple pterygium syndrome, lethal 200 cases Microlissencephaly - micromelia 2 cases form Microphthalmia - brain atrophy 3 cases Multiple sclerosis - ichthyosis - factor 2 cases 8 deficiency Microscopic polyangiitis 7,5 Multiple system atrophy 4,6 Microtia 15 MURCS association 11,25 Midas syndrome < 50 cases Muscular atrophy ataxia retinitis 10 cases Midline cleft of lower lip 70 cases pigmentosa diabetes mellitus Miller-Dieker syndrome 0,3 Muscular dystrophy congenital, with 0,03 Mirhosseini-Holmes-Walton syndrome < 15 cases integrin deficiency Mitochondrial diseases of nuclear 9 Muscular dystrophy Fukuyama type 0,54 origin Muscular dystrophy limb-girdle 0,8 Mitochondrial encephalomyopathy 2 cases aminoacidopathy Muscular dystrophy, congenital, non 0,15 merosin negative Mitochondrial myopathy with 7 cases sideroblastic anaemia Muscular dystrophy, congenital, type 0,3 1A Mitral regurgitation - deafness - 3 cases skeletal anomalies Muscular dystrophy, Duchenne and 5 Becker types Mixed dystonias 3 Families Muscular dystrophy, limb girdle, 14 cases Moebius syndrome 300 cases autosomal recessive, type 2G Mohr-Tranebjaerg syndrome 46 cases Muscular dystrophy, limb girdle, > 40 Families Monosomy 18p < 200 cases autosomal recessive, type 2I Monosomy 22q11 20 Muscular dystrophy, limb-girdle, 1 Family Monosomy 22q13 > 200 cases autosomal dominant, type 1A Monosomy 5p 4,6 Muscular dystrophy, limb-girdle, 5 Families autosomal dominant, type 1D Monosomy 9q22.3 2 cases Muscular dystrophy, limb-girdle, 5 Families Moore-Federman syndrome 6 cases autosomal dominant, type 1E Mosaic variegated aneuploidy 29 cases Muscular dystrophy, limb-girdle, 1 Family syndrome autosomal dominant, type 1F Mowat-Wilson syndrome < 200 cases Muscular dystrophy, limb-girdle, 1 Family Moya-moya disease 3,16 autosomal dominant, type 1G

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 16 Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Muscular dystrophy, tibial 6 Neurodegeneration due to 3- 2 cases hydroxyisobutyryl-CoA hydrolase Myasthenia gravis 8,5 deficiency Myasthenic syndromes, congenital 0,75 Neurodegenerative syndrome, X- 7 cases Myelodysplastic syndromes 25 linked, Bertini type Myelofibrosis with myeloid metaplasia 10 Neurodegenerative syndrome, X- 10 cases Myeloma, multiple 14,25 linked, Hamel type Myhre syndrome 15 cases Neuroectodermal endocrine syndrome 4 cases Myoclonus cerebellar ataxia deafness 4 cases Neurofibromatosis type 1 25 Myoclonus hereditary - progressive < 10 cases Neurofibromatosis type 2 0,5 distal muscular atrophy Neurometabolic disorder due to serine < 30 cases Myoneurogastrointestinal 70 cases deficiency encephalopathy syndrome Neuropathy hereditary with liability 9 Myopathy due to calsequestrin and 4 cases to pressure palsies SERCA1 protein overload Neuropathy, giant axonal 20 Families Myopathy, X-linked, with excessive 15 Families Neutropenia cyclic 0,1 autophagy Neutropenia severe congenital 0,4** N syndrome 3 cases Neutropenia, severe congenital, 7 cases N-acetyl-alpha-D-galactosaminidase 12 cases X-linked deficiency Nevo syndrome 10 cases Naegeli-Franceschetti-Jadassohn 0,035 Nevus of ota retinitis pigmentosa 1 case syndrome Niemann-Pick disease 2,5** Nail patella-like - renal disease 3 cases Niemann-Pick disease, type A 0,25** Nail-patella syndrome 2 Niemann-Pick disease, type B 0,75** Nance-Horan syndrome 50 Families Niemann-Pick disease, type C 0,85 Nanism due to growth hormone 3 cases qualitative anomaly Nijmegen breakage syndrome 1** NARP syndrome 8,5 Nodular regenerative hyperplasia of 3 the liver Nasopalpebral lipoma - coloboma - < 30 cases telecanthus Non-distal trisomy 10p 60 cases Nasopharyngeal teratoma dandy 1 case Non-distal trisomy 12p 2** walker diaphragmatic hernia Non-distal trisomy 8q > 30 cases Necrotizing encephalopathy, acute, 11 cases autosomal dominant Non-Hodgkin malignant lymphoma 36 Nemaline myopathy 1 Norrie disease 300 cases Neonatal death immune deficiency 5 cases North Carolina macular dystrophy 2 Families Neonatal hemochromatosis 100 cases Obesity - colitis - hypothyroidism - 2 cases cardiac hypertrophy - developmental Nephroblastoma 10,1 delay Nephronophtisis familial, adult form - 2 cases Obesity due to congenital leptin < 30 cases spastic quadriparesia deficiency Nephropathy - deafness - 5 cases Obesity due to prohormone 2 cases hyperparathyroidism convertase-I deficiency Nephrosis deafness urinary tract 5 cases Obesity due to pro-opiomelanocortin 7 cases digital malformations deficiency Nephrotic syndrome, idiopathic, 18 Ochoa syndrome > 100 cases steroid-sensitive Ocular albinism X-linked, recessive 2 Netherton disease 1,35 Ocular motor apraxia Cogan type 50 cases Neu-Laxova syndrome 60 cases Oculocerebrocutaneous syndrome 36 cases Neuroaxonal dystrophy renal tubular 3 cases acidosis Oculocerebrofacial syndrome, Kaufman 9 cases type Neuroblastoma 10 Oculocutaneous albinism 7,15 Neurodegeneration due to 3- 4 cases hydroxyisobutyryl-CoA hydrolase Oculodental syndrome rutherfurd 1 Family deficiency syndrome ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 17 Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Oculodentoosseous dysplasia 243 cases Osteogenesis imperfecta 6,5 dominant Osteogenesis imperfecta - 2 cases Oculodentoosseous dysplasia recessive 5 cases retinopathy - seizures - intellectual deficit Oculo-digito-esophageal-duodenal < 50 cases syndrome (ODED) Osteogenesis imperfecta, congenital - 3 cases microcephaly - cataracts Oculogastrointestinal muscular 1 Family dystrophy Osteopathia striata - cranial sclerosis 100 cases Oculo-osteo-cutaneous syndrome 3 cases Osteopetrosis autosomal dominant 33 cases type 1 Oculo-oto-facial dysplasia 4 cases Osteopetrosis lethal 2 cases Oculo-palato-cerebral syndrome 5 cases Osteopetrosis, intermediate form 50 cases Oculopharyngeal muscular dystrophy 1 Osteopetrosis, malignant 0,75** Oculo-tricho-dysplasia 2 cases Osteopoikilosis - short stature - 4 cases Odontomicronychial dysplasia 5 cases intellectual deficit Odonto-onycho-dermal dysplasia < 15 cases Osteoporosis oculocutaneous 3 cases Odonto-onycho-hypohidrotic 1 case hypopigmentation syndrome dysplasia, midline scalp defects Osteoporosis pseudoglioma syndrome 0,05 Odontotrichomelic syndrome 4 cases Osteosarcoma 5 Odonto-tricho-ungual-digito-palmarn 21 cases Osteosclerosis - ichthyosis - 3 cases syndrome premature ovarian failure Okamoto syndrome 2 cases Otodental syndrome 9 Families Oligoarticular chronic arthritis 20,5 Otopalatodigital syndrome 30 cases Oligocone trichromacy 14 cases Overhydrated hereditary 20 Families Olmsted syndrome 32 cases stomatocytosis Omodysplasia 30 cases P2Y12, deficiency of 5 cases Omphalocele 12 Pachydermoperiostosis 204 cases Omphalocele cleft palate syndrome 3 cases Pachyonychia congenita 230 cases lethal Pacman dysplasia < 10 cases Ondine syndrome 2,25 Paget disease juvenile type 50 cases Onycho-tricho-dysplasia - neutropenia 5 cases Pallister-Hall syndrome 100 cases Ophthalmo acromelic syndrome 30 cases Palmoplantar keratoderma - XX sex 5 cases Opitz BBB/G syndrome 3 reversal - predisposition to squamous cell carcinoma Opsismodysplasia 25 cases Palmoplantar porokeratosis of < 10 cases Optic atrophy 6 Mantoux Optic atrophy and cataract, autosomal 14 cases Pancreas agenesis 8 cases dominant Pancreatic hypoplasia - diabetes - < 10 cases Orbital leiomyoma 16 cases heart disease Orofaciodigital syndrome type 10 1 case Pancreatic lipomatosis duodenal 1 case stenosis Orofaciodigital syndrome type 5 4 cases Pancreatitis, hereditary 0,125 Orofaciodigital syndrome, type 1 1,2 Pancreatoblastoma 60 cases Orofaciodigital syndrome, type 3 3 cases Papillon-Lefevre syndrome 0,25 Orofaciodigital syndrome, type 4 16 cases Papulosis, malignant atrophic > 200 cases Orofaciodigital syndrome, type 6 29 cases Paraplegia - brachydactyly - cone- 5 cases Orofaciodigital syndrome, type 8 2 Families shaped epiphysis Orotic aciduria hereditary < 20 cases Paraplegia - mental retardation - 4 cases Ossification anomalies - psychomotor 2 cases hyperkeratosis development delay PARC syndrome 2 cases Osteochondritis dissecans 35 Parietal foramina 5 Osteocraniostenosis 12 cases Parkinson disease, genetic types 15 Osteodysplasty, Melnick-Needles type > 50 cases Parkinsonism, young adult onset 37,5

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 18 Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Paroxysmal extreme pain disorder 4 Families Polyarthritis, rheumatoid factor- 4,2 positive Paroxysmal nocturnal hemoglobinuria 0,55 Polycystic kidney disease, autosomal 6,5 Parsonage-Turner syndrome 3,3 recessive Partington syndrome 2 Families Polycystic lipomembranous 0,15 Pearson syndrome 60 cases osteodysplasia with sclerosing Pelizaeus-Merzbacher disease 0,25 leukoencephalopathy PELVIS syndrome 11 cases Polycystic ovaries - urethral sphincter 33 cases dysfunction Pemphigus paraneoplastic > 60 cases Polycythemia vera 25 Pemphigus superficial 1,2 Polydactyly preaxial 25 Pemphigus vulgaris 3,8 Polymorphic catecholergic ventricular 10 Pendred syndrome 5,5 tachycardia Pericarditis arthropathy < 30 Families Polymyositis 14,8 camptodactyly syndrome Polysyndactyly - cardiac malformation 6 cases Perinatal-lethal Gaucher disease 0,01 Pontocerebellar hypoplasia type 1 6 Families Peritoneal leiomyomatosis, 100 cases disseminated Pontocerebellar hypoplasia type 2 < 30 cases Perlman syndrome < 20 cases Pophyria, acute hepatic 8 Persistent hyperinsulinemic 2 Porphyria, chronic hepatic 1,5 hypoglycemia of infancy Porphyria, congenital erythropoietic > 200 cases Persistent Mullerian duct syndrome < 200 cases Posterior column ataxia - retinitis 13 cases Peters-plus syndrome 50 cases pigmentosa Peutz-Jeghers syndrome 2,2 Post-transplant lymphoproliferative 26,2 disease Pfeiffer syndrome 0,38 Potocki-Shaffer syndrome 23 cases Pfeiffer-type cardiocranial syndrome < 10 cases Prader-Willi syndrome 10,7 PHACE syndrome 100 cases Preauricular pits renal disease 1 case Phaeochromocytoma and 10 paraganglioma, secreting Primary biliary cirrhosis 13,5 Phenylketonuria 4 Primary ciliary dyskinesia 5 Phosphoenolpyruvate carboxykinase < 10 cases Primary lateral sclerosis 1,5 (PEPCK) deficiency Primary sclerosing cholangitis 11 Phosphoglycerate kinase 1 deficiency 23 cases Progeria 0,25** Phosphoribosylpyrophosphate < 30 Families Progeria - short stature - pigmented < 10 cases synthetase superactivity nevi Phytosterolemia 40 cases Progressive bulbar paralysis of < 40 cases childhood PIBIDS syndrome 20 cases Progressive neurodegeneration - joint 2 cases Piebaldism 0,25 laxity - cataract Pierre Robin syndrome 8,75 Progressive vertebral fusion, non- 10 cases Pierson syndrome 22 cases infectious, syndromic form Progressive vertebral fusion, non- 10 cases Pili torti - onychodysplasia 1 Family infectious, syndromic form Pilodental dysplasia with refractive 2 cases Prolidase deficiency 50 cases errors Propionic acidemia 3,75 Pityriasis rubra pilaris 48 cases Proteus syndrome 200 cases Plummer-Vinson syndrome 25 cases Protoporphyria, erythropoietic 0,65 Poikiloderma of Kindler 100 cases Proximal myotonic myopathy 1 Poland anomaly 2 Proximal spinal muscular atrophy 3 Pollitt syndrome 10 cases Proximal spinal muscular atrophy, 0,26 Polyarteritis nodosa 3,07 type 1 Polyarthritis, rheumatic factor- 8 Proximal spinal muscular atrophy, 2,6 negative type 2

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 19 Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Proximal spinal muscular atrophy, 2,6 Renal-hepatic-pancreatic dysplasia - 10 cases type 3 Dandy-Walker cysts Proximal spinal muscular atrophy, 0,32 Rendu-Osler-Weber disease 3,5 type 4 Renpenning syndrome 10 Families Pseudoachondroplasia 3 Restrictive cardiomyopathy, idiopathic 2,5 Pseudoarthrosis of clavicle, congenital > 200 cases or familial Pseudodiastrophic dysplasia 10 cases Retinal arteries, tortuosity of 100 cases Pseudohypoaldosteronism type 1 70 cases Retinal degeneration nanophthalmos 7 cases glaucoma Pseudoprogeria syndrome 2 cases Retinitis pigmentosa 27,5 Pseudoxanthoma elasticum 2,5 Retinitis pigmentosa - intellectual 2 Families Pseudo-Zellweger syndrome < 10 cases deficit - deafness - hypogenitalism Psoriatic arthritis, juvenile form 4,2 Retinoblastoma 5,4 Psychomotor retardation due to 3 cases Retinohepatoendocrinologic syndrome 7 cases S-adenosylhomocysteine hydrolase deficiency Retinoschisis, X-linked 4,5 Pterygium colli - intellectual deficit - 2 cases Rett syndrome 4,15 digital anomalies Rhabdoid tumors 500 cases Pterygium popliteal syndrome, 0,3 Rheumatic fever 5 autosomal dominant Rheumatoid purpura 8,5 Pterygium syndrome, antecubital 11 cases Rhombencephalosynapsis 50 cases Ptosis - strabismus - ectopic pupils 1 Family Rickettsialpox > 800 cases Ptosis - strabismus - rectus abdominis 2 cases diastasis Ring chromosome 10 < 20 cases Pulmonary alveolar proteinosis 0,1 Ring chromosome 14 50 cases Pulmonary arterial hypertension 1,5 Ring chromosome 17 14 cases Pulmonary fibrosis, idiopathic 27 Ring chromosome 20 > 50 cases Pulmonary haemosiderosis, primary 250 cases Roberts syndrome 100 cases Pulmonary lymphangiectasia, > 100 cases Robinow-like syndrome 2 cases congenital Rothmund-Thomson syndrome 300 cases Pulmonary valve stenosis, congenital 7,2 Rubella panencephalitis > 20 cases Pure autonomic failure 0,3 Rubinstein-Taybi like, syndrome 8 cases Pyogenic arthritis - pyoderma 34 cases gangrenosum - acne Rubinstein-Taybi syndrome 1 Pyruvate kinase deficiency 0,4 Rudiger syndrome 2 cases Qazi-Markouizos syndrome 3 cases Sacral hemangiomas - multiple 5 cases congenital abnormalities Radiation proctitis 35 Saethre-Chotzen syndrome 3 Radio-ulnar synostosis - < 20 cases amegakaryocytic thrombocytopenia Sakati-Nyhan syndrome < 5 cases Rambaud galian syndrome 3 cases Sandhoff disease 0,75 RAPADILINO syndrome < 20 cases Sarcoidosis 15 Rapid-onset dystonia-parkinsonism 3 Families Sarcosinemia 2 Rapp-Hodgkin syndrome 72 cases Say barber miller syndrome 2 cases Rasmussen subacute encephalitis > 100 cases Scalp defects - postaxial polydactyly 2 cases Recurrent infections - short stature - 4 cases Scalp-ear-nipple syndrome 30 cases hypopigmentation - coarse face SCARF syndrome 2 cases Refsum disease 0,1 Schinzel syndrome < 10 Families Refsum disease, infantile form 0,005 Schinzel-Giedion midface retraction 34 cases Regional odontodysplasia 139 cases syndrome Relapsing polychondritis 3,5 Schizencephaly 1,54 Renal adysplasia 26 Schizophrenia - mental retardation - 1 Family Renal agenesis, bilateral 17 deafness - retinitis ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 20 Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Schnitzler syndrome 50 cases Small vessel disease of the brain, not 2 cases NOTCH3-related Schopf-Schulz-Passarge syndrome 19 cases Smith-Lemli-Opitz syndrome 6,5 Schwartz-Jampel syndrome 100 cases Smith-Magenis syndrome 4 Scleroderma 42 Soft tissue sarcomas 13 Sebastian syndrome < 10 Families Sotos syndrome 7** Seckel syndrome 100 cases Sparse hair - short stature - skin 4 cases Segmental odontomaxillary dysplasia 32 cases anomalies Seizures - intellectual deficit due to 3 cases Spastic paraplegia - glaucoma - 2 Families hydroxylysinuria intellectual deficit Senior-Loken syndrome 0,1 Spastic paraplegia nephritis deafness 4 cases Sensenbrenner syndrome 15 cases Spastic paraplegia, familial 5 Sensorineural hearing loss, early 3 cases Spastic quadriplegia retinitis 2 cases greying, and essential tremor pigmentosa mental retardation Serpentine fibula polycystic kidneys 6 cases Spasticity - mental retardation - 6 cases Severe achondroplasia - 4 cases epilepsy, X-linked developmental delay - acanthosis Spherocytosis hereditary 20 nigricans Severe combined immunodeficiency 0,22 Spinal muscular atrophy - Dandy- 2 cases due to adenosine deaminase Walker complex - cataracts deficiency Spinocerebellar ataxia X-linked, type 5 cases Severe combined immunodeficiency 0,35 3 T- B- Spinocerebellar ataxia, infantile onset 21 cases Severe combined immunodeficiency 1,5 Split hand - split foot 1,1 T- B+, X-linked Split hand - split foot - deafness 22 cases Sezary’s syndrome 0,18 Split hand urinary anomalies spina 3 cases Short stature - pituitary and 1 Family bifida cerebellar defects - small sella turcica Spondyloenchondrodysplasia 36 cases Short stature - webbed neck - heart 4 cases disease Spondylometaphyseal dysplasia 0,34 Short stature brussels type 2 cases Spondylometaphyseal dysplasia - 8 cases cone-rod dystrophy Short stature due to growth hormone 0,2 resistance Spondylometaphyseal dysplasia with 4 cases combined immunodeficiency Short stature mental retardation eye 3 cases anomalies cleft lip palate Spontaneous periodic hypothermia < 30 cases SHORT syndrome 30 cases Sporotrichosis 55 cases Shprintzen-Goldberg syndrome < 50 cases Squamous cell carcinoma of head and 46 Shwachman-diamond syndrome 200 cases neck Sialidosis type 1 0,02** Stargardt disease 11,25 Sialidosis type 2 0,02** Steinert myotonic dystrophy 4,5 Sickle cell anaemia 11 Sternal cleft < 2 Siegler brewer carey syndrome 2 cases Stern-Lubinsky-Durrie syndrome 7 cases Silent sinus syndrome 98 cases Steroid dehydrogenase deficiency - 1 Family dental anomalies Sillence syndrome 5 cases Stickler syndrome 13,5 Silver-Russell dwarfism 400 cases Stiff-man syndrome 0,1 Simpson-Golabi-Behmel syndrome > 100 cases Simpson-Golabi-Behmel syndrome, 4 cases Stimmler syndrome 2 cases type 2 Stoll alembik finck syndrome 1 case Singleton-Merten dysplasia < 10 cases Subcorneal pustular dermatosis 200 cases Sirenomelia 1** Succinic acidemia 50 cases Sjögren-Larsson syndrome 0,4 Succinyl-CoA acetoacetate transferase 10 cases Skeletal dysplasia - intellectual deficit 2 Families deficiency

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 21 Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Sucrase-isomaltase deficiency, 20 Tracheobronchomegaly < 100 cases congenital Transmissible spongiform 0,3 Summitt syndrome 3 cases encephalopathies Supranuclear palsy, progressive 5 Treacher-Collins syndrome 6 Supravalvar aortic stenosis 12,5 Treft-Sanborn-Carey syndrome 23 cases Susac syndrome < 100 cases Tricho oculo dermo vertebral 1 case syndrome Symmetrical thalamic calcifications 29 cases Tricho onycho hypohidrotic dysplasia 1 case Sympathetic ophthalmia 0,6 Trichodental syndrome < 5 Families Symphalangism distal < 5 Families Tricho-dento-osseous syndrome > 30 cases Symphalangism with multiple 6 cases anomalies of hands and feet Trichodysplasia - amelogenesis 1 Family imperfecta Synostoses, multiple 20 Families Trichomegaly retina pigmentary 11 cases Synspondylism 24 cases degeneration dwarfism Syringomyelia 8,4 Tricho-odonto-onychial dysplasia 4 cases Systemic mastocytosis 0,33 Tricho-retino-dento-digital syndrome 9 cases Systemic vasculitis 6,3 Trichorhinophalangeal syndrome, type > 100 cases Takayasu arteritis 0,45 1 and 3 Talo-patello-scaphoid osteolysis 2 cases Tricuspid atresia 5 Tangier disease > 70 cases Trigonocephaly - bifid nose - acral 2 cases Taurodontia - absent teeth - sparse < 15 cases anomalies hair Trigonocephaly - broad thumbs 2 cases Tay-Sachs disease 0,3** Trigonocephaly - short stature - 3 cases Terminal osseous dysplasia - 18 cases developmental delay pigmentary defects Trigonocephaly ptosis coloboma 8 cases Tetraamelia - pulmonary hypoplasia 5 Families Triose phosphate-isomerase deficiency 30 cases Tetralogy of Fallot 45 Triphalangeal thumbs - 4 Families Thalidomide embryopathy 5000 cases brachyectrodactyly Thanatophoric dwarfism 3,5** Triple A syndrome 100 cases Thiamine-responsive megaloblastic 30 Families Triple H (HHH) syndrome 50 cases anaemia syndrome Triplo-X syndrome 42,5 Thomsen and Becker disease 5 Trisomy 13 13** Thrombocythemia, essential 27,5 Trisomy 18 9** Thrombocytopenic purpura, 10 Tritanopia 4,8 autoimmune True hermaphrodism > 500 cases Thumb absent short stature immune 3 cases Tuberculosis 20 deficiency Tuberous sclerosis 8,8 Thumb stiffness - brachydactyly - 6 cases mental retardation Tubular renal disease - 2 cases cardiomyopathy Thymic renal anal lung dysplasia 3 cases Tufted angioma > 200 cases Thyrocerebrorenal syndrome 2 cases Turner syndrome 20 Thyroid carcinoma, anaplastic 0,13 Tyrosinemia type 1 0,05 Thyroid carcinoma, medullary 7 Tyrosinemia type 2 < 100 cases Thyrotoxic periodic paralysis 2 Uhl anomaly 84 cases Tietz syndrome 1 Family Ulbright hodes syndrome 3 cases Toriello-Carey syndrome 60 cases Ullrich, congenital muscular dystrophy < 100 cases Toriello-Lacassie-Droste syndrome 10 cases Ulnar / fibula ray defect - 1 Family Torticollis keloids cryptorchidism 7 cases brachydactyly renal dysplasia Umbilical cord ulceration - intestinal 15 cases Townes-Brocks syndrome 0,42 atresia Tracheal agenesis 1** Unverricht-Lundborg disease 0,2 ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 22 Disease name Estimated Number of Disease name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Upington disease 1 Family Wiedemann-Rautenstrauch syndrome 25 cases Usher syndrome 3,5 Willebrand disease 12,5 VACTERL with hydrocephalus < 10 Families Williams syndrome 13,3 Van den Bosch syndrome 1 Family Wilson disease 5,84 Van Der Woude syndrome 2 Wilson-Turner syndrome > 14 cases VATER association 23 Winchester disease 12 cases Vernal keratoconjunctivitis 10 Wiskott-Aldrich syndrome 0,15 Visceral neuropathy - brain 2 cases Wolcott-Rallison syndrome 17 cases anomalies - facial dysmorphism - Wolf-Hirschhorn syndrome 2** developmental delay Wolfram syndrome 0,57 Von Hippel-Lindau disease 0,2 Wolman disease 0,28** Vulvovaginal gingival syndrome 127 cases Woolly hair - hypotrichosis - everted 1 Family W syndrome 6 cases lower lip - outstanding ears Waardenburg syndrome 2,4 Woolly hair - palmoplantar < 20 cases Waardenburg-Shah syndrome 50 cases keratoderma - dilated cardiomyopathy Waldenström macroglobulinemia 2,6 Wrinkly skin syndrome < 30 cases Walker-Warburg syndrome 1,65** Xanthomatosis cerebrotendinous 0,13 Weaver syndrome 30 cases Xeroderma pigmentosum 0,5 Weaver-Williams syndrome 2 cases Xeroderma talipes enamel defects 2 cases Wegener granulomatosis 6,6 XK aprosencephaly < 10 cases Weill-Marchesani syndrome 128 cases X-linked dominant chondrodysplasia 0,5 Wells syndrome 80 cases punctata Werner syndrome 0,45 X-linked lymphoproliferative disease 0,1 West syndrome 3,7** Zellweger syndrome 1,1 Western equine encephalitis > 600 cases Zellweger-like syndrome, without 2 cases WHIM syndrome 40 cases peroxisomal anomalies Whipple disease 1000 cases Zollinger-Ellison syndrome 5,3 Wieacker-Wolff syndrome 6 cases Zunich-Kaye syndrome 6 cases ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 23 List of diseases by decreasing prevalence Diseases with prevalence data available

Disease name Estimated Disease name Estimated prevalence prevalence (/100,000) (/100,000) Gelineau disease 49 Atresia of small intestine 20 Melanoma, familial 46,8 Atrioventricular canal, partial 20 Squamous cell carcinoma of head and neck 46 Gastric cancer 20 Autism 45 Hirschsprung disease 20 Tetralogy of Fallot 45 Monosomy 22q11 20 Arrhythmogenic right ventricular dysplasia 43,5 Spherocytosis hereditary 20 Meniere’s disease 42,5 Sucrase-isomaltase deficiency, congenital 20 Triplo-X syndrome 42,5 Tuberculosis 20 Chromosome Y deletion 42 Turner syndrome 20 Scleroderma 42 Corpus callosum agenesis neuronopathy 19 Familial venous malformations 40 Nephrotic syndrome, idiopathic, steroid-sensitive 18 Fetal cytomegalovirus syndrome 40 Cardiomyopathy, familial dilated 17,5 Parkinsonism, young adult onset 37,5 Boutonneuse fever 17 Follicular lymphoma 36 Breast cancer, familial 17 Non-Hodgkin malignant lymphoma 36 Renal agenesis, bilateral 17 Osteochondritis dissecans 35 Ichthyosis, X-linked 16,6 Radiation proctitis 35 MELAS syndrome 16 Adactylia unilateral 34 Leucinosis 15,6 Cryptosporidiosis 34 Acyl-CoA dehydrogenase, medium chain, deficiency 15 of Malignant hyperthermia 33 Atrioventricular canal, complete 15** Charcot-Marie-Tooth disease 32,5 Diaphragmatic hernia, congenital 15 Great vessels transposition (TGV) 32,5 Lennox-Gastaut syndrome 15 B-cell chronic lymphocytic leukemia 32 Acute Respiratory Distress Syndrome, Adult 30 Microtia 15 Arthrogryposis multiplex congenita 30 Parkinson disease, genetic types 15 Marfan syndrome 30 Sarcoidosis 15 Hypothyroidism, congenital 29 Dermatomyositis 14,8 Retinitis pigmentosa 27,5 Polymyositis 14,8 Thrombocythemia, essential 27,5 Fragile X syndrome 14,25 Pulmonary fibrosis, idiopathic 27 Myeloma, multiple 14,25 Post-transplant lymphoproliferative disease 26,2 Anophthalmia - Microphthalmia, isolated 14 Renal adysplasia 26 Cystinuria 14 Esophageal atresia 25 Primary biliary cirrhosis 13,5 Long QT syndrome, familial 25 Stickler syndrome 13,5 Myelodysplastic syndromes 25 Williams syndrome 13,3 Neurofibromatosis type 1 25 Androgen insensitivity syndrome 13 Polycythemia vera 25 Bronchopulmonary dysplasia 13 Polydactyly preaxial 25 Soft tissue sarcomas 13 Anorectal malformation 24 Trisomy 13 13** Legg-Calve-Perthes disease 23 Buerger’s disease 12,5 VATER association 23 Ehlers-Danlos syndrome type 3 12,5 Oligoarticular chronic arthritis 20,5 Supravalvar aortic stenosis 12,5 Dermatitis herpetiformis 20,2 Willebrand disease 12,5

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 24 Disease name Estimated Disease name Estimated prevalence prevalence (/100,000) (/100,000) Cystic fibrosis 12 Hyperlipidemia type 3 7,8 Gastroschisis 12 Hemophilia 7,7 Gonadal dysgenesis, XX type 12 Kallmann syndrome 7,7 Omphalocele 12 Acute lymphoblastic leukemia 7,5 Focal dystonia 11,7 Immunodeficiency, common variable 7,5 MURCS association 11,25 Microscopic polyangiitis 7,5 Stargardt disease 11,25 Beckwith-Wiedemann syndrome 7,3 Glioblastoma 11 Pulmonary valve stenosis, congenital 7,2 Hepatic venoocclusive disease 11 Oculocutaneous albinism 7,15 Multiple endocrine neoplasia type 1 11 Acute non lymphoblastic leukemia 7 Primary sclerosing cholangitis 11 Cerebellar ataxia, autosomal recessive 7 Sickle cell anaemia 11 Cystathioninuria 7 Prader-Willi syndrome 10,7 Facioscapulohumeral muscular dystrophy 7 Alopecia totalis 10,5 Fryns syndrome 7** Collagenous colitis 10,5 Holoprosencephaly 7 Hodgkin lymphoma 10,5 Sotos syndrome 7** Nephroblastoma 10,1 Thyroid carcinoma, medullary 7 3-methylglutaconic aciduria, type 3 10 Iminoglycinuria 6,68 Adrenal hyperplasia, congenital 10 Cat-scratch disease 6,6 Bone tumor 10 Galactosemia 6,6 Cholangiocarcinoma 10 Wegener granulomatosis 6,6 Dermatofibrosarcoma protuberans 10 Angelman syndrome 6,5 Distal myopathy, Welander type 10 Carcinoma of the gallbladder 6,5 Duane syndrome 10 Hemiplegic migraine, familial 6,5 Factor II deficiency 10 Leber hereditary optic neuropathy 6,5 Myelofibrosis with myeloid metaplasia 10 Osteogenesis imperfecta 6,5 Neuroblastoma 10 Polycystic kidney disease, autosomal recessive 6,5 Phaeochromocytoma and paraganglioma, secreting 10 Smith-Lemli-Opitz syndrome 6,5 Polymorphic catecholergic ventricular tachycardia 10 Ectopia lentis isolated 6,4 Thrombocytopenic purpura, autoimmune 10 Juvenile idiopathic arthritis, systemic-onset 6,3 Vernal keratoconjunctivitis 10 Systemic vasculitis 6,3 Mayer-Rokitansky-Küster-Hauser syndrome 9 Huntington disease 6,2 Mitochondrial diseases of nuclear origin 9 Amyotrophic lateral sclerosis 6 Neuropathy hereditary with liability to pressure 9 Cerebral arteriovenous fistula 6 palsies Digitotalar dysmorphism 6 Trisomy 18 9** Leukemia, chronic myeloid 6 Giant cell arteritis 8,9 Muscular dystrophy, tibial 6 Tuberous sclerosis 8,8 Optic atrophy 6 Pierre Robin syndrome 8,75 Treacher-Collins syndrome 6 Duodenal atresia 8,55 Wilson disease 5,84 Myasthenia gravis 8,5 Arthritis-related enthesitis 5,7 NARP syndrome 8,5 Biliary atresia 5,6 Rheumatoid purpura 8,5 Pendred syndrome 5,5 Syringomyelia 8,4 Retinoblastoma 5,4 Acute promyelocytic leukemia 8 Alzheimer disease, familial 5,3 Esophageal carcinoma 8 Zollinger-Ellison syndrome 5,3 Polyarthritis, rheumatic factor-negative 8 Cornelia de Lange syndrome 5,25 Pophyria, acute hepatic 8 Familial adenomatous polyposis 5,25

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 25 Disease name Estimated Disease name Estimated prevalence prevalence (/100,000) (/100,000) Acromegaly 5 Ehlers-Danlos syndrome, classic type 3,5 Adrenoleukodystrophy, X-linked 5 Goldenhar syndrome 3,5 Epiphyseal dysplasia multiple 5 MASA syndrome 3,5 Fructose intolerance 5 Relapsing polychondritis 3,5 Hydrolethalus 5** Rendu-Osler-Weber disease 3,5 Lung cancer, small cell 5 Thanatophoric dwarfism 3,5** Muscular dystrophy, Duchenne and Becker types 5 Usher syndrome 3,5 Osteosarcoma 5 Graft versus host disease 3,4 Parietal foramina 5 Choroidal dystrophy, central areolar 3,33 Primary ciliary dyskinesia 5 Hypochondroplasia 3,3 Rheumatic fever 5 Multiple endocrine neoplasia, type 2 3,3 Spastic paraplegia, familial 5 Parsonage-Turner syndrome 3,3 Supranuclear palsy, progressive 5 Anencephaly 3,2** Thomsen and Becker disease 5 Moya-moya disease 3,16 Tricuspid atresia 5 Acatalasemia 3,1 Tritanopia 4,8 Polyarteritis nodosa 3,07 Acrocephalosyndactyly 4,6 Bacterial toxic-shock syndrome 3 Monosomy 5p 4,6 Frontotemporal dementia 3 Multiple system atrophy 4,6 Nodular regenerative hyperplasia of the liver 3 Achondroplasia 4,5 Opitz BBB/G syndrome 3 Congenital lobar emphysema 4,5 Proximal spinal muscular atrophy 3 Retinoschisis, X-linked 4,5 Pseudoachondroplasia 3 Steinert myotonic dystrophy 4,5 Saethre-Chotzen syndrome 3 Best disease 4,4 Kennedy disease 2,8 Chronic inflammatory demyelinating polyneuropathy 4,4 Leigh syndrome 2,75** Polyarthritis, rheumatoid factor-positive 4,2 Proximal spinal muscular atrophy, type 2 2,6 Psoriatic arthritis, juvenile form 4,2 Proximal spinal muscular atrophy, type 3 2,6 Hemimelia 4,15 Waldenström macroglobulinemia 2,6 Rett syndrome 4,15 Amaurosis congenita of Leber 2,5 Amniotic bands 4** Behcet disease 2,5 Autoimmune polyendocrinopathy, type 1 4 BOR syndrome 2,5 Ceroid lipofuscinosis, neuronal 4 Bullous pemphigoid 2,5 Corticobasal degeneration 4 Cone rod dystrophy 2,5 Exostoses, multiple 4 Epidermolysis bullosa, epidermolytic 2,5 Hartnup syndrome 4 Friedreich ataxia 2,5 Histidinemia 4 Fructose-1,6-bisphosphatase deficiency 2,5 Idiopathic hypersomnia 4 Heterotaxia 2,5 Meckel syndrome 4** Niemann-Pick disease 2,5** Phenylketonuria 4 Pseudoxanthoma elasticum 2,5 Smith-Magenis syndrome 4 Restrictive cardiomyopathy, idiopathic or familial 2,5 Mantle cell lymphoma 3,9 Meconium aspiration syndrome 2,44 Acute interstitial pneumonia 3,8 Waardenburg syndrome 2,4 Anisakiasis 3,8 3-methylcrotonylglycinuria 2,25 Calpainopathy 3,8 Ondine syndrome 2,25 Pemphigus vulgaris 3,8 Peutz-Jeghers syndrome 2,2 Propionic acidemia 3,75 Cerebellar ataxia, autosomal dominant 2,15 West syndrome 3,7** GRACILE syndrome 2,12** Diastrophic dwarfism 3,5 Alport syndrome 2

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 26 Disease name Estimated Disease name Estimated prevalence prevalence (/100,000) (/100,000) Choroideremia 2 Kabuki syndrome 1,16 Coats disease 2 Glycogen storage disease type 2 1,1 Crouzon disease 2 Mucopolysaccharidosis type 3 1,1 Giant pigmented hairy nevus 2 Split hand - split foot 1,1 Kearns-Sayre syndrome 2 Zellweger syndrome 1,1 Klippel feil syndrome 2 Medullary cystic kidney disease, autosomal recessive 1,05 Langerhans cell histiocytosis 2 Cutis verticis gyrata - mental deficit 1,02 Lateral body wall complex 2** 3-hydroxyacyl-CoA dehydrogenase, long chain, 1 deficiency of Nail-patella syndrome 2 Acanthamoeba keratitis 1 Non-distal trisomy 12p 2** Adrenocortical carcinoma 1 Ocular albinism X-linked, recessive 2 Albers-Schonberg disease 1 Persistent hyperinsulinemic hypoglycemia of infancy 2 Angioedema 1 Poland anomaly 2 Ataxia telangiectasia 1 Sarcosinemia 2 Chondrodysplasia punctata, rhizomelic type 1 Thyrotoxic periodic paralysis 2 Van Der Woude syndrome 2 Chronic hiccup 1 Wolf-Hirschhorn syndrome 2** Churg-Strauss syndrome 1 Sternal cleft < 2 Clouston syndrome 1 Gamma-sarcoglycanopathy 1,96 Coloboma, ocular 1 Gastrointestinal stromal tumor 1,8 Congenital rubella syndrome 1** Muenke syndrome 1,8** Dyserythropoietic anaemia, congenital 1 Amoebiasis due to free-living amoebae 1,75 Ehlers-Danlos syndrome type 4 1 Aniridia 1,75 Endocrine tumour 1 Fabry disease 1,75 Fanconi anaemia 1 2,8 dihydroxyadenine urolithiasis 1,7 Gaucher disease 1 Kaposi’s sarcoma 1,7 Gorlin syndrome 1 Walker-Warburg syndrome 1,65** Harding ataxia 1 Schizencephaly 1,54 Holt-Oram syndrome 1 Antisynthetase syndrome 1,5 Hypokalemic periodic paralysis 1 Budd-Chiari syndrome 1,5 Isovaleric acidemia 1 CDG syndrome 1,5** Lambert-Eaton myasthenic syndrome 1 Darier disease 1,5 Macrophagic myofasciitis 1 Femur-fibula-ulna complex 1,5 Nemaline myopathy 1 Laryngo-tracheo-esophageal cleft 1,5 Nijmegen breakage syndrome 1** Multifocal motor neuropathy with conduction block 1,5 Oculopharyngeal muscular dystrophy 1 Porphyria, chronic hepatic 1,5 Proximal myotonic myopathy 1 Primary lateral sclerosis 1,5 Rubinstein-Taybi syndrome 1 Pulmonary arterial hypertension 1,5 Sirenomelia 1** Severe combined immunodeficiency T- B+, X-linked 1,5 Tracheal agenesis 1** Alagille syndrome 1,4 Acalvaria < 1** Cat-eye syndrome 1,35 Gaucher disease type 1 0,94 Netherton disease 1,35 Lewis-Sumner syndrome 0,9 Mucopolysaccharidosis type 1 1,3 MERRF syndrome 0,9 Apert syndrome 1,25 Joubert syndrome 0,85 Maternal hyperphenylalaninemia 1,25 Niemann-Pick disease, type C 0,85 Adult Onset Still’s disease 1,23 Bardet-Biedl syndrome 0,8 Orofaciodigital syndrome, type 1 1,2 Criss-cross heart 0,8 Pemphigus superficial 1,2 Muscular dystrophy limb-girdle 0,8

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 27 Disease name Estimated Disease name Estimated prevalence prevalence (/100,000) (/100,000) Cutaneous mastocytosis 0,75 Lesch-Nyhan syndrome 0,38 Ebstein anomaly 0,75 Pfeiffer syndrome 0,38 Hepatitis, chronic autoimmune 0,75 Campomelic dysplasia 0,35 Hyperkalemic periodic paralysis 0,75 Christ-Siemens-Touraine syndrome 0,35 Krabbe disease 0,75** Severe combined immunodeficiency T- B- 0,35 Myasthenic syndromes, congenital 0,75 Spondylometaphyseal dysplasia 0,34 Niemann-Pick disease, type B 0,75** Lamellar ichthyosis > 0,33 Osteopetrosis, malignant 0,75** Systemic mastocytosis 0,33 Sandhoff disease 0,75 Blackfan-Diamond disease 0,32 Albright hereditary osteodystrophy 0,72 Proximal spinal muscular atrophy, type 4 0,32 Carbamoylphosphate synthetase deficiency 0,7 Alkaptonuria 0,3 Menkes syndrome 0,7 Aortic arch interruption 0,3** Protoporphyria, erythropoietic 0,65 Dopa-responsive dystonia 0,3 Goodpasture syndrome 0,64 Emery-Dreifuss muscular dystrophy 0,3 Glycogen storage disease type 4 0,6 Miller-Dieker syndrome 0,3 Hyperlipoproteinemia type 1 0,6 Muscular dystrophy, congenital, type 1A 0,3 Mucopolysaccharidosis type 2 0,6 Pterygium popliteal syndrome, autosomal dominant 0,3 Sympathetic ophthalmia 0,6 Pure autonomic failure 0,3 Alpha-sarcoglycanopathy 0,57 Tay-Sachs disease 0,3** Beta-sarcoglycanopathy 0,57 Transmissible spongiform encephalopathies 0,3 Delta-sarcoglycanopathy 0,57 Dentatorubral pallidoluysian atrophy < 0,3 Wolfram syndrome 0,57 Wolman disease 0,28** Cantrell pentalogy 0,55** Epidermolysis bullosa, dystrophic 0,27 Coffin-Lowry syndrome 0,55 Proximal spinal muscular atrophy, type 1 0,26 Paroxysmal nocturnal hemoglobinuria 0,55 Factor VII deficiency 0,25 Muscular dystrophy Fukuyama type 0,54 Lipodystrophy, Berardinelli type 0,25 Cutaneous neuroendocrine carcinoma 0,5 Niemann-Pick disease, type A 0,25** Cystinosis 0,5 Papillon-Lefevre syndrome 0,25 Diabetes insipidus, nephrogenic 0,5 Pelizaeus-Merzbacher disease 0,25 Neurofibromatosis type 2 0,5 Piebaldism 0,25 Xeroderma pigmentosum 0,5 Progeria 0,25** X-linked dominant chondrodysplasia punctata 0,5 Leptospirosis 0,24 Inclusion body myositis, IBM 0,49 Severe combined immunodeficiency due to 0,22 adenosine deaminase deficiency Agammaglobulinemia X-linked 0,45 Acrodermatitis enteropathica, zinc deficiency type 0,2 Cowden syndrome 0,45 Diabetes mellitus, neonatal 0,2 Takayasu arteritis 0,45 Granulomatous disease, chronic 0,2 Werner syndrome 0,45 Hyperglycinemia, isolated nonketotic 0,2 Townes-Brocks syndrome 0,42 Hyperoxaluria 0,2 Aplastic anaemia 0,4 Incontinentia pigmenti 0,2 Bullous ichthyosiform erythroderma congenita 0,4 Jeune syndrome 0,2 Early onset torsion dystonia 0,4 Short stature due to growth hormone resistance 0,2 Glutaryl-CoA dehydrogenase deficiency 0,4 Unverricht-Lundborg disease 0,2 Homocystinuria due to cystathionine beta-synthase 0,4 deficiency Von Hippel-Lindau disease 0,2 Mucopolysaccharidosis type 4 0,4 Lowe syndrome 0,19 Neutropenia severe congenital 0,4** Sezary’s syndrome 0,18 Pyruvate kinase deficiency 0,4 Atypical coarctation of aorta 0,17** Sjögren-Larsson syndrome 0,4 Metachromatic leukodystrophy 0,16

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 28 Disease name Estimated Disease name Estimated prevalence prevalence (/100,000) (/100,000) Mucopolysaccharidosis type 6 0,16** Neutropenia cyclic 0,1 Epilepsy, pyridoxin-dependent 0,15 Pulmonary alveolar proteinosis 0,1 Fibrinogen deficiency, congenital 0,15 Refsum disease 0,1 Mucolipidosis type 2 0,15** Senior-Loken syndrome 0,1 Muscular dystrophy, congenital, non merosin 0,15 Stiff-man syndrome 0,1 negative X-linked lymphoproliferative disease 0,1 Polycystic lipomembranous osteodysplasia with 0,15 sclerosing leukoencephalopathy Crigler-Najjar syndrome < 0,1 Wiskott-Aldrich syndrome 0,15 Lafora disease < 0,1 CHARGE association 0,14 Fibrodysplasia ossificans progressiva 0,08 Thyroid carcinoma, anaplastic 0,13 Epidermolysis bullosa, junctional 0,06 Xanthomatosis cerebrotendinous 0,13 Mendelian susceptibility to atypical mycobacteria 0,059 Pancreatitis, hereditary 0,125 Aceruloplasminemia 0,05 Bartter syndrome 0,12 Botulism 0,05 Lissencephaly type 2 0,12 Chordoma 0,05 Medullary cystic kidney disease, autosomal 0,11 Craniofacial dyssynostosis 0,05 dominant, with or without hyperuricemia Gaucher disease, type 3 0,05 Alpha-mannosidosis 0,1 Osteoporosis pseudoglioma syndrome 0,05 Creutzfeldt-Jakob disease 0,1 Tyrosinemia type 1 0,05 Diffuse leiomyomatosis - Alport syndrome X-linked 0,1 Fibrous dysplasia of bone < 0,05 Distal myopathy, Nonaka type 0,1 Factor XIII deficiency, congenital 0,04 Dyskeratosis congenita 0,1 Naegeli-Franceschetti-Jadassohn syndrome 0,035 Evans syndrome 0,1 Muscular dystrophy congenital, with integrin 0,03 Ewing sarcoma 0,1 deficiency Factor V deficiency 0,1 Alpers syndrome 0,025 Factor XI deficiency, congenital 0,1 Sialidosis type 1 0,02** Familial cold urticaria 0,1 Sialidosis type 2 0,02** Hemophilia, acquired 0,1 Gaucher disease type 2 0,01 Leprechaunism 0,1** Perinatal-lethal Gaucher disease 0,01 Lymphangioleiomyomatosis 0,1 Refsum disease, infantile form 0,005

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 29 List of diseases by reported number of published cases Diseases without prevalence data available. Report on number of published cases

Disease name Number of Disease name Number of published cases published cases or families or families Thalidomide embryopathy 5000 cases Muir-Torre syndrome 205 cases Angio-osteohypertrophic syndrome 1000 cases Pachydermoperiostosis 204 cases Whipple disease 1000 cases Aarskog-Scott syndrome > 200 cases Alveolar echinococcosis < 1000 cases Blue rubber bleb nevus > 200 cases Esthesioneuroblastoma < 1000 cases Erythrokeratodermia variabilis, Mendes da Costa > 200 cases type Rickettsialpox > 800 cases Fetal methyl mercury syndrome 800 cases Monosomy 22q13 > 200 cases Western equine encephalitis > 600 cases Papulosis, malignant atrophic > 200 cases Enchondromatosis 600 cases Porphyria, congenital erythropoietic > 200 cases Familial dysautonomia 550 cases Pseudoarthrosis of clavicle, congenital > 200 cases Adamantinoma 513 cases Tufted angioma > 200 cases True hermaphrodism > 500 cases Adenosine monophosphate deaminase deficiency 200 cases Aicardi syndrome 500 cases Camurati engelmann disease 200 cases CADASIL 500 cases Cockayne syndrome 200 cases Malakoplasia 500 cases Cogan syndrome 200 cases Rhabdoid tumors 500 cases Costello syndrome 200 cases Epidermal nevus syndrome > 400 cases Eosinophilic fasciitis 200 cases Castleman disease 400 cases Glucose-galactose malabsorption 200 cases Silver-Russell dwarfism 400 cases Gorham-Stout disease 200 cases 4-hydroxybutyricaciduria 350 cases Kimura disease 200 cases Leukocyte adhesion deficiency (LAD) < 350 cases Marinesco-Sjogren syndrome 200 cases Alexander disease 300 cases Multiple pterygium syndrome, lethal form 200 cases Alström syndrome 300 cases Proteus syndrome 200 cases CDG syndrome type Ia 300 cases Shwachman-diamond syndrome 200 cases Cutis marmorata telangiectatica congenita 300 cases Subcorneal pustular dermatosis 200 cases Focal dermal hypoplasia 300 cases Monosomy 18p < 200 cases Gräsbeck-Imerslund disease 300 cases Mowat-Wilson syndrome < 200 cases Lipodystrophy, familial partial, Dunnigan type 300 cases Persistent Mullerian duct syndrome < 200 cases Melorheostosis 300 cases Hyperimmunoglobinemia D with recurrent fever 180 cases Methylmalonic acidemia - homocystinuria 300 cases Erdheim-Chester disease 178 cases Moebius syndrome 300 cases Kasabach-Merritt syndrome > 175 cases Norrie disease 300 cases Celiac disease epilepsy occipital calcifications 170 cases Rothmund-Thomson syndrome 300 cases Alpha thalassemia- mental retardation, X-linked 168 cases Lipoid proteinosis > 280 cases Carney complex 160 cases Eosinophilic gastroenteritis 280 cases McCune-Albright syndrome 158 cases Chronic recurrent multifocal osteomyelitis, juvenile > 260 cases Infantile neuroaxonal dystrophy > 150 cases Job syndrome 250 cases Ligneous conjunctivitis > 150 cases Lipodystrophy, partial acquired 250 cases Cloverleaf skull syndrome 150 cases Pulmonary haemosiderosis, primary 250 cases Denys-Drash syndrome 150 cases Caroli’s disease < 250 cases Dubowitz syndrome 150 cases 6-pyruvoyl-tetrahydropterin synthase, deficiency 248 cases Ellis Van Creveld syndrome 150 cases Oculodentoosseous dysplasia dominant 243 cases Fraser syndrome 150 cases Pachyonychia congenita 230 cases Humeroradial synostosis 150 cases Lhermitte-Duclos disease 220 cases Jacobsen syndrome 150 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 30 Disease name Number of Disease name Number of published cases published cases or families or families Arthrogryposis - renal dysfunction - cholestasis < 150 cases Seckel syndrome 100 cases Inflammatory pseudotumor of the liver 143 cases Triple A syndrome 100 cases Regional odontodysplasia 139 cases Brown-Vialetto-van Laere syndrome < 100 cases Dihydropteridine reductase deficiency 134 cases Hallermann-Streiff-Francois syndrome < 100 cases Aorto-ventricular tunnel 130 cases Hypertrichosis lanuginosa congenita < 100 cases Weill-Marchesani syndrome 128 cases Hypocomplementaemic leucocytoclasic vasculitis < 100 cases Vulvovaginal gingival syndrome 127 cases Ichthyosis congenita, harlequin type < 100 cases Bickel-Fanconi glycogenosis 112 cases Susac syndrome < 100 cases Achondrogenesis > 100 cases Tracheobronchomegaly < 100 cases Bloom syndrome > 100 cases Tyrosinemia type 2 < 100 cases Carnitine palmitoyl transferase 2 deficiency > 100 cases Ullrich, congenital muscular dystrophy < 100 cases Central neurocytoma > 100 cases Silent sinus syndrome 98 cases Cutis laxa > 100 cases Acrofacial dysostosis, Nager type 90 cases Eosinophilic pneumonia, acute idiopathic > 100 cases Megacystis microcolon - intestinal hypoperistalsis - 89 cases hydronephrosis Fetal varicella syndrome > 100 cases Early infantile epileptic encephalopathy 88 cases KID syndrome > 100 cases Glycogen storage disease due to LAMP-2 deficiency 84 cases Mucolipidosis type 4 > 100 cases Uhl anomaly 84 cases Ochoa syndrome > 100 cases Acquired generalized lipodystrophy 80 cases Pulmonary lymphangiectasia, congenital > 100 cases Metatropic dwarfism 80 cases Rasmussen subacute encephalitis > 100 cases Wells syndrome 80 cases Simpson-Golabi-Behmel syndrome > 100 cases Rapp-Hodgkin syndrome 72 cases Trichorhinophalangeal syndrome, type 1 and 3 > 100 cases LEOPARD syndrome > 70 cases Aicardi-Goutieres syndrome 100 cases Tangier disease > 70 cases Autoimmune lymphoproliferative syndrome 100 cases Bullous systemic lupus erythematosus 70 cases Bernard-Soulier syndrome 100 cases Craniometaphyseal dysplasia 70 cases Bethlem myopathy 100 cases Midline cleft of lower lip 70 cases Chaotic atrial tachycardia 100 cases Myoneurogastrointestinal encephalopathy 70 cases CINCA syndrome 100 cases syndrome Cohen syndrome 100 cases Pseudohypoaldosteronism type 1 70 cases Congenital cataracts - facial dysmorphism - 100 cases Diffuse neonatal haemangiomatosis < 70 cases neuropathy Glutathione synthetase deficiency 65 cases Defective expression of HLA class 2 100 cases Hyperferritinemia, hereditary, with congenital > 64 cases Epidermolysis bullosa, acquired 100 cases cataracts Freeman-Sheldon syndrome 100 cases Pemphigus paraneoplastic > 60 cases Fucosidosis 100 cases Cerebro-costo-mandibular syndrome 60 cases Greig syndrome 100 cases Dyggve-Melchior-Clausen disease 60 cases Immunodeficiency due to selective anti- 100 cases Griscelli disease 60 cases polysaccharide antibody deficiency Hypertrichosis lanuginosa, acquired 60 cases Internal carotid agenesis 100 cases Ketoacidosis due to betaketothiolase deficiency 60 cases Larsen syndrome 100 cases Neu-Laxova syndrome 60 cases Neonatal hemochromatosis 100 cases Non-distal trisomy 10p 60 cases Osteopathia striata - cranial sclerosis 100 cases Pancreatoblastoma 60 cases Pallister-Hall syndrome 100 cases Pearson syndrome 60 cases Peritoneal leiomyomatosis, disseminated 100 cases Toriello-Carey syndrome 60 cases PHACE syndrome 100 cases Double uterus-hemivagina-renal agenesis < 60 cases Poikiloderma of Kindler 100 cases Ataxia, autosomal recessive, Beauce type 57 cases Retinal arteries, tortuosity of 100 cases Capillary leak syndrome 57 cases Roberts syndrome 100 cases Sporotrichosis 55 cases Schwartz-Jampel syndrome 100 cases Mazabraud syndrome 54 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 31 Disease name Number of Disease name Number of published cases published cases or families or families Hennekam syndrome > 50 cases Ear-patella-short stature syndrome 42 cases Megacalycosis, congenital > 50 cases Desbuquois syndrome > 40 cases Osteodysplasty, Melnick-Needles type > 50 cases 3M syndrome 40 cases Ring chromosome 20 > 50 cases Babesiosis 40 cases Acromesomelic dysplasia, Maroteaux type 50 cases Carpenter syndrome 40 cases Acroosteolysis dominant type 50 cases Chylomicron retention disease 40 cases Adenylosuccinate lyase deficiency 50 cases Coffin-Siris syndrome 40 cases Anorchidia, bilateral 50 cases Ectodermal dysplasia, hypohidrotic, autosomal 40 cases dominant Ascher syndrome 50 cases Galloway-Mowat syndrome 40 cases Benign paroxysmal torticolis of infancy 50 cases Macrocephaly - Cutis Marmorata Telangiectatica 40 cases Cholestasis - lymphoedema, syndrome 50 cases Congenita Focal myositis 50 cases Methimazole embryofetopathy 40 cases Fronto-temporal dementia and Parkinsonism linked 50 cases Phytosterolemia 40 cases to chromosome 17 (FTDP-17) WHIM syndrome 40 cases Glucocorticoid deficiency, familial 50 cases Acromicric dysplasia < 40 cases Glucosephosphate isomerase deficiency 50 cases Arterial tortuosity < 40 cases ICF syndrome 50 cases Mucopolysaccharidosis type 7 < 40 cases Juvenile hyaline fibromatosis 50 cases Progressive bulbar paralysis of childhood < 40 cases Mucosulfatidosis 50 cases Hypotrichosis simplex 38 cases Ocular motor apraxia Cogan type 50 cases Mandibuloacral dysplasia 37 cases Osteopetrosis, intermediate form 50 cases Oculocerebrocutaneous syndrome 36 cases Paget disease juvenile type 50 cases Spondyloenchondrodysplasia 36 cases Peters-plus syndrome 50 cases Carnitine palmitoyl transferase 1 deficiency 35 cases Prolidase deficiency 50 cases Cobb syndrome 35 cases Rhombencephalosynapsis 50 cases Hereditary sensory and autonomic neuropathy, 35 cases Ring chromosome 14 50 cases type 2 Schnitzler syndrome 50 cases Acrocallosal syndrome, Schinzel type 34 cases Succinic acidemia 50 cases Antley-Bixler syndrome 34 cases Triple H (HHH) syndrome 50 cases Pyogenic arthritis - pyoderma gangrenosum - acne 34 cases Waardenburg-Shah syndrome 50 cases Schinzel-Giedion midface retraction syndrome 34 cases Aglossia adactylia < 50 cases Marshall-Smith syndrome 33 cases Branchio-oculo-facial syndrome < 50 cases Osteopetrosis autosomal dominant type 1 33 cases Cholesteryl ester storage disease < 50 cases Polycystic ovaries - urethral sphincter dysfunction 33 cases DOOR syndrome < 50 cases Double outlet left ventricle 32 cases Ehrlichiosis < 50 cases Olmsted syndrome 32 cases Fibular aplasia - ectrodactyly < 50 cases Segmental odontomaxillary dysplasia 32 cases Goldmann-Favre syndrome < 50 cases Argininemia 31 cases Granulomatous slack skin < 50 cases CDG syndrome type Ic > 30 cases Midas syndrome < 50 cases Non-distal trisomy 8q > 30 cases Oculo-digito-esophageal-duodenal syndrome < 50 cases Tricho-dento-osseous syndrome > 30 cases (ODED) Agnathia holoprosencephaly situs inversus 30 cases Shprintzen-Goldberg syndrome < 50 cases Anophthalmia - hypothalamo-pituitary 30 cases Corticosteroid-sensitive aseptic abscesses 49 cases insufficiency Pityriasis rubra pilaris 48 cases Camptodactyly - tall stature - scoliosis - hearing 30 cases Coxo-podo-patellar syndrome 47 cases loss Mohr-Tranebjaerg syndrome 46 cases Carnitine-acylcarnitine translocase deficiency 30 cases Encephalo cranio cutaneous lipomatosis 45 cases Carnosinemia 30 cases KBG syndrome 45 cases Cataract cardiomyopathy 30 cases Bowen-Conradi syndrome 44 cases CHILD syndrome 30 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 32 Disease name Number of Disease name Number of published cases published cases or families or families Dermopathy restrictive lethal 30 cases Wiedemann-Rautenstrauch syndrome 25 cases Early myoclonic encephalopathy 30 cases Hepatic veno-occlusive disease - immunodeficiency < 25 cases Elejalde syndrome 30 cases Bartsocas-Papas syndrome 24 cases Geroderma osteodysplastica 30 cases Distal myopathy, with early respiratory muscle 24 cases involvement Humeroradioulnar synostosis 30 cases Synspondylism 24 cases Marden-Walker syndrome 30 cases Congenital bronchobiliary fistula 23 cases Marshall’s syndrome with periodic fever 30 cases Deletion 2q24 23 cases Mevalonicaciduria 30 cases Johanson-Blizzard syndrome 23 cases Omodysplasia 30 cases Phosphoglycerate kinase 1 deficiency 23 cases Ophthalmo acromelic syndrome 30 cases Potocki-Shaffer syndrome 23 cases Otopalatodigital syndrome 30 cases Treft-Sanborn-Carey syndrome 23 cases Scalp-ear-nipple syndrome 30 cases Acro-pectoral syndrome 22 cases SHORT syndrome 30 cases Aortic dilatation- joint hypermobility- arterial 22 cases Triose phosphate-isomerase deficiency 30 cases tortuosity Weaver syndrome 30 cases Pierson syndrome 22 cases Acropectorovertebral dysplasia < 30 cases Split hand - split foot - deafness 22 cases Congenital brain dysgenesis due to glutamine < 30 cases Craniolenticulosutural dysplasia 21 cases synthetase deficiency Dehydratase deficiency 21 cases Developmental delay due to 2-methylbutyryl-CoA < 30 cases dehydrogenase deficiency Odonto-tricho-ungual-digito-palmarn syndrome 21 cases Ectodermal dysplasia - absent dermatoglyphs < 30 cases Spinocerebellar ataxia, infantile onset 21 cases Encephalopathy due to hydroxykynureninuria < 30 cases Craniodiaphyseal dysplasia > 20 cases Frontometaphyseal dysplasia < 30 cases Fumaric aciduria > 20 cases Glycogen storage disease type 7 < 30 cases Rubella panencephalitis > 20 cases Johnson neuroectodermal syndrome < 30 cases 3-methylglutaconic aciduria, type 1 20 cases Nasopalpebral lipoma - coloboma - telecanthus < 30 cases Acrorenal syndrome 20 cases Neurometabolic disorder due to serine deficiency < 30 cases Arrhinia 20 cases Obesity due to congenital leptin deficiency < 30 cases Calvarial doughnut lesions - bone fragility 20 cases Pontocerebellar hypoplasia type 2 < 30 cases CDG syndrome type Ib 20 cases Spontaneous periodic hypothermia < 30 cases Craniofrontonasal dysplasia, Teebi type 20 cases Wrinkly skin syndrome < 30 cases Distal monosomy 8p 20 cases Cone rod dystrophy amelogenesis imperfecta 29 cases Gray platelet syndrome 20 cases Infant epilepsy with migrant focal crisis 29 cases Juvenile temporal arteritis 20 cases Mosaic variegated aneuploidy syndrome 29 cases Lacrimo-auriculo-dento-digital syndrome 20 cases Orofaciodigital syndrome, type 6 29 cases Lipoamide dehydrogenase deficiency 20 cases Symmetrical thalamic calcifications 29 cases PIBIDS syndrome 20 cases Hypertrichosis cubiti - short stature 28 cases Acromegaloid facial appearance syndrome < 20 cases Catel-Manzke syndrome 27 cases Acromegaloid facies - hypertrichosis < 20 cases GAPO syndrome 27 cases Bronchopneumopathy, chronic, due to TAP < 20 cases deficiency Geleophysic dwarfism 27 cases Carey fineman ziter syndrome < 20 cases Insomnia, familial fatal 27 cases ‘Ectodermal dysplasia, ‘’pure’’ hair-nail type’ < 20 cases Limb-mammary syndrome 27 cases Epidermolysis bullosa simplex - limb girdle < 20 cases 3C syndrome 25 cases muscular dystrophy Atelosteogenesis II 25 cases Hemorrhagic disorders due to collagen receptors < 20 cases Book syndrome 25 cases deficiency Erythrokeratodermia ataxia 25 cases Hypertrichosis, anterior cervical, isolated < 20 cases Keratoderma palmoplantar - spastic paralysis 25 cases Ichthyosis bullosa of Siemens < 20 cases Opsismodysplasia 25 cases IMAGe syndrome < 20 cases Plummer-Vinson syndrome 25 cases Interstitial granulomatous dermatitis with arthritis < 20 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 33 Disease name Number of Disease name Number of published cases published cases or families or families Laryngeal abductor paralysis - mental retardation < 20 cases Odonto-onycho-dermal dysplasia < 15 cases Lipodystrophy, familial partial, Köbberling type < 20 cases Taurodontia - absent teeth - sparse hair < 15 cases Metaphyseal anadysplasia < 20 cases Wilson-Turner syndrome > 14 cases Orotic aciduria hereditary < 20 cases ADULT syndrome 14 cases Perlman syndrome < 20 cases Anophthalmia/microphthalmia - esophageal atresia 14 cases Radio-ulnar synostosis - amegakaryocytic < 20 cases Atkin-Flaitz syndrome 14 cases thrombocytopenia Beta-mannosidosis 14 cases RAPADILINO syndrome < 20 cases DEND syndrome 14 cases Ring chromosome 10 < 20 cases Dermo-odonto dysplasia 14 cases Woolly hair - palmoplantar keratoderma - dilated < 20 cases Fingerprints absence - congenital milia 14 cases cardiomyopathy Muscular dystrophy, limb girdle, autosomal 14 cases 6q terminal deletion 19 cases recessive, type 2G Amelo-cerebro-hypohidrotic syndrome 19 cases Oligocone trichromacy 14 cases Craniosynostosis, Boston type 19 cases Optic atrophy and cataract, autosomal dominant 14 cases Hereditary inclusion body myopathy - joint 19 cases Ring chromosome 17 14 cases contractures - ophthalmoplegia Aromatase deficiency 13 cases Schopf-Schulz-Passarge syndrome 19 cases Chondrodysplasia, Blomstrand type 13 cases Crisponi syndrome 18 cases Diaphragmatic hernia - exomphalos - corpus 13 cases Hypertrichotic osteochondrodysplasia 18 cases callosum agenesis Terminal osseous dysplasia - pigmentary defects 18 cases Hypotelorism - cleft palate - hypospadias 13 cases Aminopterin embryofetopathy 17 cases Posterior column ataxia - retinitis pigmentosa 13 cases Erythroderma lethal congenital 17 cases Acro-pectoro-renal field defect 12 cases Folate malabsorption, hereditary 17 cases Alopecia- epilepsy - pyorrhea - mental 12 cases GTP cyclohydrolase I deficiency 17 cases subnormality Hypokeratosis, palmo-plantar, circumscribed 17 cases Ataxia - deafness - optic atrophy, lethal 12 cases Malonic aciduria 17 cases Atelosteogenesis I 12 cases Mental retardation, X linked, with seizures, short 17 cases Atelosteogenesis III 12 cases stature, and midface hypoplasia Atrial tachyarrhythmia with short pr interval 12 cases Wolcott-Rallison syndrome 17 cases Coloboma of macula - brachydactyly type B 12 cases Acromegaly - cutis verticis gyrata - corneal 16 cases Coloboma uveal with cleft lip palate and mental 12 cases leukoma retardation Antley-Bixler-like syndrome - ambiguous 16 cases Distal myopathy with posterior leg and anterior 12 cases genitalia - disordered steroidogenesis upper limb involvement Glycogen storage, type 0 16 cases Distal myopathy with vocal cord weakness 12 cases Mental retardation, X-linked - Dandy Walker 16 cases Dopamine beta-hydroxylase deficiency 12 cases malformation - Basal ganglia disease - Seizures Hypoparathyroidism, deafness and renal disease 12 cases Mental retardation, X-linked, South African type 16 cases (HDR) Metaphyseal chondrodysplasia, Jansen type 16 cases Mental retardation, X-linked - macrocephaly - 12 cases Microgastria - limb reduction defect 16 cases macro-orchidism Orbital leiomyoma 16 cases N-acetyl-alpha-D-galactosaminidase deficiency 12 cases Orofaciodigital syndrome, type 4 16 cases Osteocraniostenosis 12 cases Ablepharon macrostomia syndrome 15 cases Winchester disease 12 cases Angel-shaped phalango-epiphyseal dysplasia 15 cases Anonychia - onychodystrophy with hypoplasia or 11 cases absence of distal phalanges IBIDS syndrome 15 cases Atrial septal defect atrioventricular conduction 11 cases Myhre syndrome 15 cases Corpus callosum dysgenesis, X-linked recessive 11 cases Sensenbrenner syndrome 15 cases Fibrochondrogenesis 11 cases Umbilical cord ulceration - intestinal atresia 15 cases Fibular dimelia - diplopodia 11 cases Congenital anosmia, isolated < 15 cases Foveal hypoplasia presenile cataract 11 cases Immunodeficiency due to interleukin-1 receptor- < 15 cases associated kinase-4 deficiency Fuhrmann syndrome 11 cases Mirhosseini-Holmes-Walton syndrome < 15 cases Lopez-Hernandez syndrome 11 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 34 Disease name Number of Disease name Number of published cases published cases or families or families Mental retardation, X-linked, Snyder type 11 cases Renal-hepatic-pancreatic dysplasia - Dandy-Walker 10 cases cysts Necrotizing encephalopathy, acute, autosomal 11 cases dominant Succinyl-CoA acetoacetate transferase deficiency 10 cases PELVIS syndrome 11 cases Toriello-Lacassie-Droste syndrome 10 cases Pterygium syndrome, antecubital 11 cases Aase-Smith syndrome < 10 cases Trichomegaly retina pigmentary degeneration 11 cases Acrofacial dysostosis Rodriguez type < 10 cases dwarfism Acromelanosis < 10 cases CHAND syndrome > 10 cases Astley-Kendall dysplasia < 10 cases Chediak-Higashi syndrome > 10 cases Carpo tarsal osteochondromatosis < 10 cases Median cleft of the upper lip - corpus callosum > 10 cases Carpo tarsal osteolysis recessive < 10 cases lipoma - cutaneous polyps Cerebral gigantism - jaw cysts < 10 cases Acromesomelic dysplasia Hunter-Thompson type 10 cases Corneal dystrophy - perceptive deafness < 10 cases Albright like syndrome 10 cases Deafness - lymphoedema - leukemia < 10 cases Ambras syndrome 10 cases Diaphanospondylodysostosis < 10 cases Arthrogryposis multiplex congenita -whistling face 10 cases Digitorenocerebral syndrome < 10 cases Athabaskan brainstem dysgenesis syndrome 10 cases Gaucher disease - ophthalmoplegia - cardiovascular < 10 cases Barber-Say syndrome 10 cases calcification Boomerang dysplasia 10 cases Glomerulonephritis sparse hair telangiectases < 10 cases Cardiac conduction disease, dilated 10 cases Greenberg dysplasia < 10 cases cardiomyopathy and brachydactyly Hypopituitarism - microphthalmia < 10 cases Cataract mental retardation hypogonadism 10 cases Myoclonus hereditary - progressive distal muscular < 10 cases Cerebro-oculo-nasal syndrome 10 cases atrophy Char syndrome 10 cases Pacman dysplasia < 10 cases Charcot-Marie-Tooth disease - nephropathy 10 cases Palmoplantar porokeratosis of Mantoux < 10 cases Choroido cerebral calcification syndrome infantile 10 cases Pancreatic hypoplasia - diabetes - heart disease < 10 cases form Pfeiffer-type cardiocranial syndrome < 10 cases Colobomatous microphthalmia heart disease 10 cases Phosphoenolpyruvate carboxykinase (PEPCK) < 10 cases hearing loss deficiency Distal monosomy 5q 10 cases Progeria - short stature - pigmented nevi < 10 cases Ectodermal dysplasia - skin fragility syndrome 10 cases Pseudo-Zellweger syndrome < 10 cases Flynn aird syndrome 10 cases Singleton-Merten dysplasia < 10 cases Goldberg-Shprintzen megacolon syndrome 10 cases XK aprosencephaly < 10 cases Hyperkeratosis - hyperpigmentation syndrome 10 cases Ataxia - apraxia - mental retardation, X-linked 9 cases Atransferrinemia 9 cases Ichthyosis follicularis - atrichia - photophobia 10 cases Bosley-Salih-Alorainy syndrome 9 cases Iris coloboma with ptosis - intellectual deficit 10 cases Brachymorphism - onychodysplasia - 9 cases Juberg hayward syndrome 10 cases dysphalangism Lipodystrophy, familial partial, associated with 10 cases Cardiomyopathy - cataract - hip spine disease 9 cases PPARG mutations Gamma-glutamylcysteine synthetase deficiency 9 cases Mental retardation, X-linked - hypotonia - facial 10 cases dysmorphism - aggressive behavior Guanidinoacetate methyltransferase deficiency 9 cases Mental retardation, X-linked, syndromic 7 10 cases Macrostomia - preauricular tags - external 9 cases ophthalmoplegia Muscular atrophy ataxia retinitis pigmentosa 10 cases diabetes mellitus Mental retardation, X-linked, Shashi type 9 cases Neurodegenerative syndrome, X-linked, Hamel type 10 cases Microdontia - type I microtia - deafness 9 cases Nevo syndrome 10 cases Oculocerebrofacial syndrome, Kaufman type 9 cases Tricho-retino-dento-digital syndrome 9 cases Pollitt syndrome 10 cases 5-oxoprolinase deficiency 8 cases Progressive vertebral fusion, non-infectious, 10 cases syndromic form Ackerman syndrome 8 cases Progressive vertebral fusion, non-infectious, 10 cases Ankylosing vertebral hyperostosis with tylosis 8 cases syndromic form Ataxia-deafness-retardation syndrome 8 cases Pseudodiastrophic dysplasia 10 cases Campomelia Cumming type 8 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 35 Disease name Number of Disease name Number of published cases published cases or families or families Camptodactyly syndrome guadalajara type 1 8 cases Biliary tract malformation - renal failure 6 cases COACH syndrome 8 cases Blepharophimosis - ptosis - esotropia - 6 cases syndactyly - short stature Corpus callosum, agenesis - cataract - 8 cases immunodeficiency CDG syndrome type Ig 6 cases Deafness skeletal dysplasia lip granuloma 8 cases Cutis gyrata acanthosis nigricans craniosynostosis 6 cases Familial hematuria, autosomal dominant - retinal 8 cases Deafness, enamel hypoplasia, nail defects 6 cases arteriolar tortuosity - contractures Eiken syndrome 6 cases Hydrocephalus - costovertebral dysplasia - 8 cases Sprengel anomaly Epilepsy telangiectasia 6 cases Hypomyelination - congenital cataract 8 cases Fanconi ichthyosis dysmorphism 6 cases Kallmann syndrome - heart disease 8 cases Grange syndrome 6 cases Mental retardation, X-linked - dysmorphism - 8 cases Hidrotic ectodermal dysplasia type Christianson- 6 cases cerebral atrophy Fourie Mental retardation, X-linked, Abidi type 8 cases Hypopituitarism - postaxial polydactyly 6 cases Mental retardation, X-linked, Vitale type 8 cases Isotretinoin-like syndrome 6 cases Micro syndrome 8 cases Keratosis follicularis - dwarfism - cerebral atrophy 6 cases Pancreas agenesis 8 cases Megalencephaly - polymicrogyria - post-axial 6 cases Rubinstein-Taybi like, syndrome 8 cases polydactyly - hydrocephalus Spondylometaphyseal dysplasia - cone-rod 8 cases Mental retardation sparse hair brachydactyly 6 cases dystrophy Mental retardation X-linked - psychosis - 6 cases Trigonocephaly ptosis coloboma 8 cases macroorchidism Acro-renal-mandibular syndrome 7 cases Mental retardation, X-linked, Armfield type 6 cases Albinism ocular - late onset sensorineural deafness 7 cases Mental retardation, X-linked, Zorick type 6 cases Branchial arch syndrome, X-linked 7 cases Moore-Federman syndrome 6 cases Cardiogenital syndrome 7 cases Polysyndactyly - cardiac malformation 6 cases CDG syndrome type Ie 7 cases Serpentine fibula polycystic kidneys 6 cases CEDNIK syndrome 7 cases Spasticity - mental retardation - epilepsy, X-linked 6 cases Cleft palate lateral synechia syndrome 7 cases Symphalangism with multiple anomalies of hands 6 cases Dihydropyrimidinuria 7 cases and feet Ehlers-Danlos syndrome type 7C 7 cases Thumb stiffness - brachydactyly - mental 6 cases retardation Gamma-glutamyl transpeptidase deficiency 7 cases W syndrome 6 cases Genitopatellar syndrome 7 cases Wieacker-Wolff syndrome 6 cases Lenz-Majewski hyperostotic dwarfism 7 cases Zunich-Kaye syndrome 6 cases MEHMO syndrome 7 cases Achalasia - microcephaly 5 cases MEHMO syndrome 7 cases Acro-fronto-facio-nasal dysostosis 5 cases Mental retardation, X-linked, severe, Gustavson 7 cases type Adducted thumbs-arthrogryposis, Dundar type 5 cases Michels syndrome 7 cases Alopecia - contractures - dwarfism - mental 5 cases retardation Mitochondrial myopathy with sideroblastic anaemia 7 cases Anonychia microcephaly 5 cases Multiple fibrofolliculoma familial 7 cases Arachnodactyly ossification abnormal mental 5 cases Neurodegenerative syndrome, X-linked, Bertini type 7 cases retardation Neutropenia, severe congenital, X-linked 7 cases Aurocephalosyndactyly 5 cases Obesity due to pro-opiomelanocortin deficiency 7 cases Bamforth syndrome 5 cases Retinal degeneration nanophthalmos glaucoma 7 cases Beta-ureidopropionase deficiency 5 cases Retinohepatoendocrinologic syndrome 7 cases Bradyopsia 5 cases Stern-Lubinsky-Durrie syndrome 7 cases Branchiogenic deafness syndrome 5 cases Torticollis keloids cryptorchidism renal dysplasia 7 cases CAMOS syndrome 5 cases 3-hydroxy 3-methylglutaryl-CoA (HMG) synthase 6 cases CDG syndrome type Id 5 cases Acrofacial dysostosis catania form 6 cases CDG syndrome type Ih 5 cases Agonadism - dextrocardia - diaphragmatic hernia 6 cases Choanal atresia - deafness - cardiac defects - 5 cases Aplasia cutis congenita of limbs recessive 6 cases dysmorphism

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 36 Disease name Number of Disease name Number of published cases published cases or families or families Cleft palate - cardiac defect - genital anomalies - 5 cases Arterial dissection - lentiginosis 4 cases ectrodactyly Benign exophthalmos syndrome 4 cases Craniosynostosis - dysmorphism - brachydactyly 5 cases Bone dysplasia lethal holmgren type 4 cases Curry-Jones syndrome 5 cases Bone fragility, craniosynostosis, proptosis, 4 cases Dacryocystitis osteopoikilosis 5 cases hydrocephalus Depigmentation of the iris, acute, bilateral 5 cases Bonnemann-Meinecke-Reich syndrome 4 cases Dermatoosteolysis Kirghizian type 5 cases Brachydactyly long thumb type 4 cases Ectrodactyly - ectodermal dysplasia without 5 cases Caudal dysgenesis familial type 4 cases clefting CDG syndrome type If 4 cases Fine-Lubinsky syndrome 5 cases CDG syndrome type IIa 4 cases German syndrome 5 cases CDG syndrome type Ik 4 cases Glaucoma - sleep apnoea 5 cases Cholestasis pigmentary retinopathy cleft palate 4 cases Humerospinal dysostosis 5 cases Chondrodysplasia lethal recessive 4 cases Humeroulnar synostosis 5 cases Choroideremia deafness obesity 4 cases Hypothyroidism - dysmorphism - postaxial 5 cases Cleft lip and palate malrotation cardiopathy 4 cases polydactyly - intellectual deficit Coxoauricular syndrome 4 cases Ichthyosis - male hypogonadism 5 cases Cranio osteoarthropathy 4 cases Keratoderma - epithelioma - dental abnormalities- 5 cases hypogonadism Craniodigital syndrome mental retardation 4 cases Lymphoedema - cerebral arteriovenous anomaly 5 cases Craniofaciocardioskeletal syndrome 4 cases Matthew-Wood syndrome 5 cases Craniosynostosis dandy walker hydrocephalus 4 cases Mental retardation, X-linked - choreoathesis - 5 cases Deafness - peripheral neuropathy - arterial disease 4 cases abnormal behavior Diabetes mellitus, permanent neonatal - pancreatic 4 cases Mental retardation, X-linked - cubitus valgus - 5 cases and cerebellar agenesis dysmorphism Diaphragmatic defect - limb deficiency - skull 4 cases Mental retardation, X-linked, Lubs type 5 cases defect Neonatal death immune deficiency 5 cases Duker-Weiss-Siber syndrome 4 cases Nephropathy - deafness - hyperparathyroidism 5 cases Ectodermal dysplasia berlin type 4 cases Nephrosis deafness urinary tract digital 5 cases Ectopia lentis chorioretinal dystrophy myopia 4 cases malformations Facial onset sensory and motor neuronopathy 4 cases Oculodentoosseous dysplasia recessive 5 cases Gombo syndrome 4 cases Oculo-palato-cerebral syndrome 5 cases Gorlin-Chaudhry-Moss, syndrome 4 cases Odontomicronychial dysplasia 5 cases Growth delay - intellectual deficit - 4 cases Onycho-tricho-dysplasia - neutropenia 5 cases mandibulofacial dysostosis - microcephaly - cleft P2Y12, deficiency of 5 cases palate Palmoplantar keratoderma - XX sex reversal - 5 cases Growth retardation - microcephaly - digital 4 cases predisposition to squamous cell carcinoma abnormalities - hypospadias Paraplegia - brachydactyly - cone-shaped epiphysis 5 cases Hidrotic ectodermal dysplasia Halal type 4 cases Sacral hemangiomas - multiple congenital 5 cases Homocarnosinosis 4 cases abnormalities Hypogammaglobulinemia due to CD19 deficiency 4 cases Sillence syndrome 5 cases Hypomandibular faciocranial dysostosis 4 cases Spinocerebellar ataxia X-linked, type 3 5 cases Hypomyelination - hypogonadotropic 4 cases Cystic hamartoma of lung and kidney < 5 cases hypogonadism - hypodontia Lathosterolosis < 5 cases Hypomyelination - hypogonadotropic 4 cases hypogonadism - hypodontia Sakati-Nyhan syndrome < 5 cases Hypotrichosis - lymphoedema - telangiectasia 4 cases Abruzzo-Erickson syndrome 4 cases Ichthyosis alopecia eclabion ectropion mental 4 cases Acrofacial dysostosis, palagonia type 4 cases retardation Anophthalmia plus syndrome 4 cases Immunodeficiency with natural-killer cell 4 cases Aortic arch anomaly peculiar facies mental 4 cases deficiency retardation Leukodystrophy with oligodontia 4 cases Aplasia cutis - myopia 4 cases Leukoencephalopathy - metaphyseal 4 cases Arhinia choanal atresia microphthalmia 4 cases chondrodysplasia

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 37 Disease name Number of Disease name Number of published cases published cases or families or families Leukoencephalopathy - palmoplantar keratoderma 4 cases Anonychia with flexural pigmentation 3 cases Liver disease - retitinitis pigmentosa - 4 cases Anophthalmia - megalocornea - cardiopathy - 3 cases polyneuropathy - epilepsy skeletal anomalies Macrogyria pseudobulbar palsy 4 cases Aphalangy - hemivertebrae - urogenital-intestinal 3 cases dysgenesis Malignant hyperthermia - arthrogryposis - 4 cases torticollis Aplasia cutis congenita - intestinal 3 cases lymphangiectasia Mental retardation - dysmorphism - 4 cases hypogonadism - diabetes mellitus Arachnodactyly - mental retardation - dysmorphism 3 cases Mental retardation, X-linked - hypogonadism - 4 cases AREDYLD syndrome 3 cases ichthyosis - obesity - short stature Axenfeld-Rieger anomaly - hydrocephaly - skeletal 3 cases Mental retardation, X-linked - seizures - psoriasis 4 cases abnormalities Mental retardation, X-linked, Miles-Carpenter type 4 cases Blepharoptosis - myopia - ectopia lentis 3 cases Mental retardation, X-linked, Schimke type 4 cases Branchio-skeleto-genital syndrome 3 cases Mental retardation, X-linked, Seemanova type 4 cases Buttiens-Fryns syndrome 3 cases Mental retardation, X-linked, Siderius type 4 cases Camptodactyly - fibrous tissue hyperplasia - 3 cases skeletal dysplasia Mental retardation, X-linked, Stevenson type 4 cases Cataract deafness hypogonadism 3 cases Mental retardation, X-linked, Stocco Dos Santos 4 cases type Cervical hypertrichosis - peripheral neuropathy 3 cases Mental retardation, X-linked, Stoll type 4 cases Cortical blindness - mental retardation - 3 cases polydactyly Metaphyseal acroscyphodysplasia 4 cases Cranio fronto nasal dysplasia poland anomaly 3 cases Microcephalic osteodysplastic dysplasia, Saul- 4 cases Wilson type Craniofacial dysmorphism - coloboma - corpus 3 cases callosum agenesis Microcephaly micropenis convulsions 4 cases Craniofacial-deafness-hand syndrome 3 cases Multiple pterygium syndrome, autosomal dominant 4 cases Craniosynostosis - intracranial calcifications 3 cases Myoclonus cerebellar ataxia deafness 4 cases Cutaneous albinism, ermine phenotype 3 cases Myopathy due to calsequestrin and SERCA1 protein 4 cases overload Cutaneous photosensitivity colitis lethal 3 cases Neurodegeneration due to 3-hydroxyisobutyryl-CoA 4 cases Deafness - opticoacoustic nerve atrophy - 3 cases hydrolase deficiency dementia Neuroectodermal endocrine syndrome 4 cases Deafness-mental retardation, Martin-Probst type 3 cases Oculo-oto-facial dysplasia 4 cases Deafness-mental retardation, Martin-Probst type 3 cases Odontotrichomelic syndrome 4 cases Disorder of sex development - mental retardation 3 cases Orofaciodigital syndrome type 5 4 cases Ectodermal dysplasia, hypohidrotic - 3 cases Osteopoikilosis - short stature - intellectual deficit 4 cases hypothyroidism - ciliary dyskinesia Paraplegia - mental retardation - hyperkeratosis 4 cases Ectodermic dysplasia hypothyroidism cleft 3 cases Recurrent infections - short stature - 4 cases Eyebrow duplication syndactyly 3 cases hypopigmentation - coarse face Facial dysmorphism macrocephaly myopia dandy 3 cases Severe achondroplasia - developmental delay - 4 cases walker acanthosis nigricans Faciocardiomelic dysplasia lethal 3 cases Short stature - webbed neck - heart disease 4 cases Gardner-Morrison-Abbott syndrome 3 cases Simpson-Golabi-Behmel syndrome, type 2 4 cases Glaucoma - ectopia - microspherophakia - stiff 3 cases Sparse hair - short stature - skin anomalies 4 cases joints - short stature Spastic paraplegia nephritis deafness 4 cases Global developmental delay - osteopenia - 3 cases ectodermal defect Spondylometaphyseal dysplasia with combined 4 cases immunodeficiency Goodman syndrome 3 cases Tricho-odonto-onychial dysplasia 4 cases Hair defect photosensitivity mental retardation 3 cases Acromesomelic dysplasia brahimi bacha type 3 cases Hirschsprung disease - nail hypoplasia - 3 cases dysmorphism Agammaglobulinemia - microcephaly - 3 cases craniosynostosis - severe dermatitis Hypogonadism - retinitis pigmentosa 3 cases Amelia, autosomal recessive 3 cases Lewis-Pashayan syndrome 3 cases Aniridia absent patella 3 cases Lipodystrophy - mental retardation - deafness 3 cases Aniridia ptosis mental retardation obesity familial 3 cases Lumbosacral vertebrae, posterior fusion of - 3 cases type blepharoptosis

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 38 Disease name Number of Disease name Number of published cases published cases or families or families Malabsorptive diarrhea due to paucity of 3 cases Acrofacial dysostosis autosomal recessive 2 cases enteroendocrine cells, congenital Agenesis of the corpus callosum - mental 2 cases Mental retardation - hypoplastic corpus callosum - 3 cases retardation - coloboma - micrognathia preauricular tag Alar cartilages hypoplasia - coloboma - telecanthus 2 cases Mental retardation, X linked - precocious puberty - 3 cases Alopecia - hypogonadism - extrapyramidal disorder 2 cases obesity Amaurosis - hypertrichosis 2 cases Mental retardation, X-linked - 3 cases hypogammaglobulinemia - progressive neurological Aniridia renal agenesis psychomotor retardation 2 cases deterioration Aniridia-mental retardation syndrome 2 cases Mental retardation, X-linked, Shrimpton type 3 cases Arthrogryposis - hyperkeratosis, lethal form 2 cases Mental retardation, X-linked, Wilson type 3 cases Atherosclerosis- deafness - diabetes - epilepsy - 2 cases Mental retardation, X-linked, Wittwer type 3 cases nephropathy Microcephaly - cleft palate 3 cases Aughton syndrome 2 cases Microcephaly cardiomyopathy 3 cases Auricular abnormalities - cleft lip with or without 2 cases cleft palate - ocular abnormalities Microcytic anaemia - liver iron overload - low 3 cases ferritinemia Auriculoocular anomalies - cleft lip 2 cases Microphthalmia - brain atrophy 3 cases Bangstad syndrome 2 cases Mitral regurgitation - deafness - skeletal anomalies 3 cases Beemer-Ertbruggen syndrome 2 cases Mullerian derivatives - lymphangiectasia - 3 cases Blepharo-facio-skeletal syndrome 2 cases polydactyly Bouwes Bavinck syndrome 2 cases N syndrome 3 cases Brachytelephalangy - dysmorphism - Kallmann 2 cases Nail patella-like - renal disease 3 cases syndrome Nanism due to growth hormone qualitative 3 cases Braddock syndrome 2 cases anomaly Brain malformation - congenital heart disease - 2 cases Neuroaxonal dystrophy renal tubular acidosis 3 cases postaxial polydactyly Oculo-osteo-cutaneous syndrome 3 cases Camptodactyly syndrome, Guadalajara type 2 2 cases Omphalocele cleft palate syndrome lethal 3 cases Cardiomyopathy - renal anomalies 2 cases Orofaciodigital syndrome, type 3 3 cases Cataract - microphthalmia - septal defect 2 cases Osteogenesis imperfecta, congenital - 3 cases Cataract - nephropathy - encephalopathy 2 cases microcephaly - cataracts Cataract- ataxia - deafness 2 cases Osteoporosis oculocutaneous hypopigmentation 3 cases CDG syndrome type IIe 2 cases syndrome CDG syndrome type IL 2 cases Osteosclerosis - ichthyosis - premature ovarian 3 cases failure CDG syndrome, type IIh 2 cases Psychomotor retardation due to S- 3 cases Chondrodysplasia - disorder of sex development 2 cases adenosylhomocysteine hydrolase deficiency Choroidal atrophy alopecia 2 cases Qazi-Markouizos syndrome 3 cases Cleft lip palate - mental retardation - corneal 2 cases Rambaud galian syndrome 3 cases opacities Seizures - intellectual deficit due to 3 cases Cleft lip retinopathy 2 cases hydroxylysinuria Cleft palate short stature vertebral anomalies 2 cases Sensorineural hearing loss, early greying, and 3 cases Cleft palate stapes fixation oligodontia 2 cases essential tremor Cleido rhizomelic syndrome 2 cases Short stature mental retardation eye anomalies 3 cases cleft lip palate Congenital ichthyosis microcephalus quadriplegia 2 cases Split hand urinary anomalies spina bifida 3 cases Contractures ectodermal dysplasia cleft lip palate 2 cases Summitt syndrome 3 cases Cooper-Jabs syndrome 2 cases Thumb absent short stature immune deficiency 3 cases Corneal anesthesia deafness mental retardation 2 cases Thymic renal anal lung dysplasia 3 cases Corneal-cerebellar syndrome 2 cases Trigonocephaly - short stature - developmental 3 cases Craniosynostosis fibular aplasia 2 cases delay Craniosynostosis radial aplasia type imaizumi 2 cases Ulbright hodes syndrome 3 cases Craniotubular syndrome 2 cases 46,XX disorders of sex development - skeletal 2 cases Cryptomicrotia - brachydactyly - excess fingertip 2 cases anomalies arch Acrocraniofacial dysostosis 2 cases Cystic hygroma lethal - cleft palate 2 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 39 Disease name Number of Disease name Number of published cases published cases or families or families Dahlberg - Borer - Newcomer, syndrome 2 cases Kniest-like dysplasia, lethal 2 cases Dandy walker macrocephaly 2 cases Kudo tamura fuse syndrome 2 cases Dandy walker malformation postaxial polydactyly 2 cases Lichstenstein syndrome 2 cases Deaf blind hypopigmentation 2 cases Low birth weight - dwarfism - 2 cases dysgammaglobulinemia Deafness - vitiligo - achalasia 2 cases Macrocephaly - immune deficiency - anemia 2 cases Deafness-tubular acidosis-anaemia 2 cases Macrocephaly - short stature - paraplegia 2 cases Dentinogenesis imperfecta - short stature - hearing 2 cases loss - mental retardation Mental retardation, X-linked - acromegaly - 2 cases hyperactivity Dermato-cardio-skeletal syndrome Borrone type 2 cases Mental retardation, X-linked - epilepsy - 2 cases Dermatoleukodystrophy 2 cases progressive joint contractures - dysmorphism Desmosterolosis 2 cases Mental retardation, X-linked - plagiocephaly 2 cases Developmental malformations - deafness - dystonia 2 cases Mental retardation, X-linked, Cantagrel type 2 cases Diabetes, neonatal - congenital hypothyroidism - 2 cases Mental retardation, X-linked, Reish type 2 cases congenital glaucoma - hepatic fibrosis - polycystic kidneys Mesomelic dysplasia skin dimples 2 cases Dincsoy-Salih-Patel syndrome 2 cases Methylmalonic aciduria - microcephaly - cataract 2 cases Duane anomaly - myopathy - scoliosis 2 cases Microbrachycephaly - ptosis - cleft lip 2 cases Dysmorphism - short stature - deafness - 2 cases Microcephaly - glomerulonephritis - marfanoid 2 cases pseudohermaphroditism habitus Ectodermal dysplasia - blindness 2 cases Microcephaly - seizures - mental retardation - 2 cases heart disease Ectodermal dysplasia, anhidrotic, with 2 cases immunodeficiency, osteopetrosis, and Microlissencephaly - micromelia 2 cases lymphoedema Mitochondrial encephalomyopathy 2 cases Eng strom syndrome 2 cases aminoacidopathy Epilepsy microcephaly skeletal dysplasia 2 cases Monosomy 9q22.3 2 cases Fuqua-Berkovitz syndrome 2 cases Multiple sclerosis - ichthyosis - factor 8 deficiency 2 cases Gamma aminobutyric acid transaminase deficiency 2 cases Nephronophtisis familial, adult form - spastic 2 cases quadriparesia Gonadal dysgenesis, XY type - associated 2 cases anomalies Neurodegeneration due to 3-hydroxyisobutyryl-CoA 2 cases hydrolase deficiency Heart defects - limb shortening 2 cases Obesity - colitis - hypothyroidism - cardiac 2 cases Hec syndrome 2 cases hypertrophy - developmental delay Hemolytic anaemia, lethal - genital anomalies 2 cases Obesity due to prohormone convertase-I deficiency 2 cases Hennekam-Beemer syndrome 2 cases Oculo-tricho-dysplasia 2 cases Hersh-Podruch-Weisskopf syndrome 2 cases Okamoto syndrome 2 cases Hirschsprung disease - deafness - polydactyly 2 cases Ossification anomalies - psychomotor development 2 cases Hydrocephaly tall stature joint laxity 2 cases delay Hypercoagulability syndrome, due to 2 cases Osteogenesis imperfecta - retinopathy - seizures - 2 cases glycosylphosphatidylinositol deficiency intellectual deficit Hypomagnesemia with normocalciuria 2 cases Osteopetrosis lethal 2 cases Hypotrichosis-mental retardation lopes type 2 cases PARC syndrome 2 cases Ichthyosis - hepatosplenomegaly - cerebellar 2 cases Pilodental dysplasia with refractive errors 2 cases degeneration Progressive neurodegeneration - joint laxity - 2 cases Ichthyosis - oral and digital anomalies 2 cases cataract Ichthyosis congenita biliary atresia 2 cases Pseudoprogeria syndrome 2 cases Inappropriate antidiuretic hormone secretion 2 cases Pterygium colli - intellectual deficit - digital 2 cases syndrome anomalies Intellectual deficit, severe - epilepsy - anal 2 cases Ptosis - strabismus - rectus abdominis diastasis 2 cases anomalies - distal phalangeal hypoplasia Robinow-like syndrome 2 cases Iris dysplasia - hypertelorism - deafness 2 cases Rudiger syndrome 2 cases Kaler garrity stern syndrome 2 cases Say barber miller syndrome 2 cases Kapur-Toriello syndrome 2 cases Scalp defects - postaxial polydactyly 2 cases Keratoderma hypotrichosis leukonychia 2 cases SCARF syndrome 2 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 40 Disease name Number of Disease name Number of published cases published cases or families or families Short stature brussels type 2 cases Preauricular pits renal disease 1 case Siegler brewer carey syndrome 2 cases Stoll alembik finck syndrome 1 case Small vessel disease of the brain, not NOTCH3- 2 cases Tricho oculo dermo vertebral syndrome 1 case related Tricho onycho hypohidrotic dysplasia 1 case Spastic quadriplegia retinitis pigmentosa mental 2 cases Li-Fraumeni syndrome 400 Families retardation Birt-Hogg-Dube syndrome > 60 Families Spinal muscular atrophy - Dandy-Walker complex - 2 cases cataracts Nance-Horan syndrome 50 Families Stimmler syndrome 2 cases Muscular dystrophy, limb girdle, autosomal > 40 Families recessive, type 2I Talo-patello-scaphoid osteolysis 2 cases Granulomatous arthritis of childhood 40 Families Thyrocerebrorenal syndrome 2 cases Erythermalgia, primary 30 Families Trigonocephaly - bifid nose - acral anomalies 2 cases LCAT deficiency 30 Families Trigonocephaly - broad thumbs 2 cases Thiamine-responsive megaloblastic anaemia 30 Families Tubular renal disease - cardiomyopathy 2 cases syndrome Visceral neuropathy - brain anomalies - facial 2 cases Pericarditis arthropathy camptodactyly syndrome < 30 Families dysmorphism - developmental delay Phosphoribosylpyrophosphate synthetase < 30 Families Weaver-Williams syndrome 2 cases superactivity Xeroderma talipes enamel defects 2 cases Neuropathy, giant axonal 20 Families Zellweger-like syndrome, without peroxisomal 2 cases Overhydrated hereditary stomatocytosis 20 Families anomalies 2,4-dienoyl-CoA reductase deficiency 1 case Synostoses, multiple 20 Families 46 xx gonadal dysgenesis epibulbar dermoid 1 case Acro-renal-ocular syndrome < 20 Families Acrofacial dysostosis postaxial, atypical 1 case Fahr syndrome < 20 Families Acrofacial dysostosis, Preis type 1 case Familial platelet syndrome with predisposition to < 20 Families acute myelogenous leukemia Anophthalmia - short stature - obesity 1 case Ichthyosis prematurity syndrome 16 Families Blaichman syndrome 1 case Myopathy, X-linked, with excessive autophagy 15 Families Bone dysplasia azouz type 1 case Familial platelet syndrome with predisposition to 13 Families Bone dysplasia corpus callosum agenesis 1 case acute myelogenous leukemia Cataract - hypertrichosis - intellectual deficit 1 case Marie Unna congenital hypotrichosis 12 Families CDG syndrome type Ii 1 case Aniridia - cerebellar ataxia - mental deficiency > 10 Families CDG syndrome type IIb 1 case Brachydactyly - arterial hypertension > 10 Families CDG syndrome type IId 1 case Aortic aneurysm syndrome, Loeys-Dietz type 10 Families CDG syndrome type Ij 1 case Renpenning syndrome 10 Families Chondrodysplasia situs inversus imperforate anus 1 case polydactyly Acheiropodia < 10 Families Corneal dystrophy ichthyosis microcephaly mental 1 case Angioma neurocutaneous, hereditary < 10 Families retardation Focal facial dermal dysplasia < 10 Families Ectodermal dysplasia alopecia preaxial polydactyly 1 case Hypoparathyroidism familial isolated < 10 Families Ectodermal dysplasia arthrogryposis diabetes 1 case Keratoderma palmoplantar - deafness < 10 Families mellitus Keratosis palmoplantaris - esophageal carcinoma < 10 Families Ectodermal dysplasia mental retardation syndactyly 1 case Mental retardation, X-linked, syndromic, due to < 10 Families Hyaluronidase deficiency 1 case JARID1C mutation Hypothyroidism - dermoid cyst - cleft palate 1 case Schinzel syndrome < 10 Families Lissencephaly - immunodeficiency 1 case Sebastian syndrome < 10 Families Martinez monasterio pinheiro syndrome 1 case VACTERL with hydrocephalus < 10 Families Nasopharyngeal teratoma dandy walker 1 case diaphragmatic hernia Otodental syndrome 9 Families Nevus of ota retinitis pigmentosa 1 case Ankyloblepharon - ectodermal defects - cleft lip 8 Families palate Odonto-onycho-hypohidrotic dysplasia, midline 1 case scalp defects Cataract-microcornea syndrome 8 Families Orofaciodigital syndrome type 10 1 case Lethal osteosclerotic bone dysplasia 8 Families Pancreatic lipomatosis duodenal stenosis 1 case EEM syndrome 7 Families

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 41 Disease name Number of Disease name Number of published cases published cases or families or families Immune dysregulation - polyendocrinopathy - 7 Families Skeletal dysplasia - intellectual deficit 2 Families enteropathy, X linked Spastic paraplegia - glaucoma - intellectual deficit 2 Families Juvenile macular degeneration, hypotrichosis 7 Families Albinism-deafness syndrome 1 Family Cystoid macular dystrophy 6 Families Alopecia - congenita keratosis palmoplantaris 1 Family Developmental dysphasia familial 6 Families Aphalangia - syndactyly - microcephaly 1 Family Pontocerebellar hypoplasia type 1 6 Families Banki syndrome 1 Family Anaemia, sideroblastic, X-linked - ataxia 5 Families Camptobrachydactyly 1 Family Muscular dystrophy, limb-girdle, autosomal 5 Families Cerebellar ataxia, autosomal recessive - saccadic 1 Family dominant, type 1D intrusion Muscular dystrophy, limb-girdle, autosomal 5 Families Congenital alopecia, X linked 1 Family dominant, type 1E Coronary artery disease - hyperlipidemia - 1 Family Tetraamelia - pulmonary hypoplasia 5 Families hypertension - diabetes - osteoporosis Symphalangism distal < 5 Families Costocoracoid ligament congenitally short 1 Family Trichodental syndrome < 5 Families Craniofacial conodysplasia 1 Family Camptodactyly - taurinuria 4 Families Craniosynostosis, Philadelphia type 1 Family IVIC syndrome 4 Families Cyprus facial neuromusculoskeletal syndrome 1 Family Paroxysmal extreme pain disorder 4 Families Dyschondrosteosis - nephritis 1 Family Triphalangeal thumbs - brachyectrodactyly 4 Families Ehlers-Danlos syndrome type 10 1 Family Adducted thumbs - arthrogryposis, Christian type 3 Families Episodic ataxia, type 3 1 Family CAMFAK syndrome 3 Families Fried syndrome 1 Family Cataract-glaucoma 3 Families Hereditary vascular retinopathy 1 Family Cerebellar ataxia, autosomal recessive - blindness - 3 Families deafness Hereditary vascular retinopathy 1 Family Cerebroretinal vasculopathy 3 Families Hydrocephalus - blue sclerae - nephropathy 1 Family Deafness-infertility syndrome 3 Families Insulin resistance, short fifth metacarpals 1 Family HERNS syndrome 3 Families Lipodystrophy, familial partial, due to AKT2 1 Family Hypomagnesemia with hypocalciuria 3 Families mutations Mental retardation, X-linked, with isolated growth 3 Families Mental retardation - progressive spasticity, X- 1 Family hormone deficiency linked Mixed dystonias 3 Families Mental retardation, X-linked - Spastic paraplegia 1 Family with iron deposits Rapid-onset dystonia-parkinsonism 3 Families Mental retardation, X-linked recessive - 1 Family Angioma serpiginosum, familial 2 Families macrocephaly - ciliary dysfunction Ankyloblepharon filiforme - imperforate anus 2 Families Mental retardation, X-linked, Cabezas type 1 Family Bencze syndrome 2 Families Mental retardation, X-linked, Pai type 1 Family Blepharonasofacial malformation syndrome 2 Families Muscular dystrophy, limb-girdle, autosomal 1 Family Bullous dystrophy, macular type 2 Families dominant, type 1A Cerebellar ataxia - areflexia - pes cavus - optic 2 Families Muscular dystrophy, limb-girdle, autosomal 1 Family atrophy - sensorineural hearing loss dominant, type 1F Chorioretinal atrophy, progressive bifocal 2 Families Muscular dystrophy, limb-girdle, autosomal 1 Family dominant, type 1G Earlobes, thickened - conductive deafness 2 Families Oculodental syndrome rutherfurd syndrome 1 Family Ehlers-Danlos syndrome, type 5 2 Families Oculogastrointestinal muscular dystrophy 1 Family Episodic ataxia, type 4 2 Families Pili torti - onychodysplasia 1 Family Fibromatosis, gingival - progressive deafness 2 Families Ptosis - strabismus - ectopic pupils 1 Family Growth deficiency - brachydactyly - dysmorphism 2 Families Schizophrenia - mental retardation - deafness - 1 Family Hypoparathyroidism X-linked 2 Families retinitis Jackson-Weiss syndrome 2 Families Short stature - pituitary and cerebellar defects - 1 Family North Carolina macular dystrophy 2 Families small sella turcica Orofaciodigital syndrome, type 8 2 Families Steroid dehydrogenase deficiency - dental 1 Family anomalies Partington syndrome 2 Families Tietz syndrome 1 Family Retinitis pigmentosa - intellectual deficit - 2 Families deafness - hypogenitalism Trichodysplasia - amelogenesis imperfecta 1 Family

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 42 Disease name Number of published cases or families Ulnar / fibula ray defect - brachydactyly 1 Family Upington disease 1 Family Van den Bosch syndrome 1 Family Woolly hair - hypotrichosis - everted lower lip - 1 Family outstanding ears

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases.pdf 43