Preliminary report from an on going bibliographic studyinitiated by Eurordis in partnership with Orphanet

RARE DISEASES IN NUMBERSRARE DISEASES IN NUMBERS

Study objectives- To assess the prevalence in Europe of each rare disease- To document the age of onset, the life expectancy and the mode of inheritance

Study rationale- Very little documented information on the epidemiology of rare diseases- Important to estimate the total number of affected people and the prevalence per disease- Need to assess the natural history of rare diseases to adapt care and monitor improvements

Preliminary results from the analysis of 359 rare diseases Not all data were available for every diseaseMore results will be available in a few month’s time

Results

- 26.5% autosomal dominant inheritance- 28.1% autosomal recessive inheritance- 7% X-linked inheritance- 10% several modes of inheritance- 13.4% multigenic/multifactorial diseases- 8.1% sporadic diseases- 5.8% unknown aetiology

- 37.5% normal lifespan- 25.7% potentially lethal at birth or before 5 years of age- 36.8% reduced lifespan,depending on the severity, penetrance or type (child, juvenile or adult types for example) of the disease

Mode of inheritance of 359 rare diseases

Life expectancy of 323 rare diseases

0

10

20

30

40

50

60

70

0-2 3-12 13-25 adults

Age of onset of 353 rare diseases (Years)

Exclusively in the age range

Not exclusively in the age range

MethodSelection of rare disease (for the purposes of the current report)

- The most common rare diseases according to books and websites- The most frequently requested pages on the Orphanet website

Limitations of the study

- Exact prevalence rate is difficult to obtain from the available data sources - Low level of consistency between studies- Poor documentation of methods used- Confusion between incidence and prevalence - Confusion between incidence at birth and life long incidence.

Search strategy

- Several data sources: Websites: Orphanet, e-medicine, geneclinics and OMIM- Medline was 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 were also some important sources of available data.

Number ofCases

Klippel trenaunay weber syndromeWhipple diseaseIncontinentia pigmentiAicardi syndromeCADASILLi-Fraumeni syndromeSilver-Russell, syndromeCastleman diseaseCutis marmorata telangiectatica congenitaMöbius syndromeAlström syndromeKabuki syndromeOndine syndromeJob syndromeKearns-Sayre syndromeXanthomatosis cerebrotendinousCockayne syndromeGunther diseaseCogan syndromeKimura diseaseAlpha thalassemia-mental retardation, X linkedMcCune-Albright syndromeDenys-Drash syndromeCohen syndromeSeckel syndromeCINCA syndromeLarsen syndromeMacrophagic myofasciitisCapillary leak syndromeWaardenburg-Shah syndromePeters-plus syndromeCoffin-Siris syndromeAcrocallosal syndrome, Schinzel typePallister-Killian, syndromeAicardi-Goutieres syndromeCHILD syndromeSchinzel-Giedion midface retraction syndrome

10001000

750500500400400400300300300300300250223200200200200200164158150100100100100100

575050403430303030

Disease Name

2004117

Diseases without prevalence data available but with published cases

0

10

20

30

40

50

60

10-50 1-9 0.1-0.9 exceptional

%

Prevalence range of 230 rare diseases (/100,000)

Cumulative prevalence : 1.7%

%

Disease nameEstimated prevalence (/100 000)

Brugada syndrome 50Protoporphyria, erythropoietic 50Guillain-Barre syndrome 47,5Melanoma, familial 46,8Autism, genetic types 45Tetralogy of Fallot 45Scleroderma 42Great vessels transposition 32,5Focal dystonia 30Marfan syndrome 30Non-Hodgkin malignant lymphoma 30Retinitis pigmentosa 27,5Gelineau disease 26Myeloma, multiple 26Alpha-1 antitrypsin deficiency 25Diaphragmatic hernia, congenital 25Juvenile arthritis, idiopathic 25Neurofibromatosis type 1 25Oesophageal atresia 25Polycythemia vera 25Charcot-Marie-Tooth disease 24Polycystic kidney disease, recessive type 23VATER association 23Coffin-Lowry syndrome 22,5Rendu-Osler-Weber disease 21,25Dermatitis herpetiformis 20,2Atresia of small intestin 20Duodenal atresia 20Ehlers-Danlos syndrome, classic type 20Hirschsprung disease 20Microdeletion 22q11 20Spherocytosis hereditary 20Turner syndrome 20Cardiomyopathy, familial dilated 17,5Breast cancer, familial 17MELAS syndrome 16Leucinosis 15,6Acyl-CoA dehydrogenase, medium chain, deficiency of 15Lennox-Gastaut syndrome 15Fragile X syndrome 14,25Primary biliary cirrhosis 13,5Stickler syndrome 13,5Williams syndrome 13,3Willebrand disease 12,5Gastroschisis 12Microphthalmia 12Omphalocele 12Sarcoidosis 12MURCS association 11,25Stargardt disease 11,25Glioblastoma 11Multiple endocrine neoplasia type 1 11Prader-Willi syndrome 10,7Alopecia totalis 10,5Nephroblastoma 10,1Cystic fibrosis 10Duane syndrome 10Neuroblastoma 10Hodgkin disease 9,4

Disease nameEstimated prevalence (/100 000)

Dermatomyositis 9,25Polymyositis 9,25Tuberous sclerosis 8,8Congenital adrenal hyperplasia 8,5Rett syndrome 8,2Angelman syndrome 8Cataract, total congenital 7,9Hyperlipidemia type 3 7,8Hemophilia 7,7Trisomy 18 7,7Behcet disease 7,5Immunodeficiency, common variable 7,5Microscopic polyangiitis 7,5Idiopathic torsion dystonia 7,25Oculocutaneous albinism 7,15Facioscapulohumeral muscular dystrophy 7Holoprosencephaly 7Sclerosing cholangitis 7Sotos syndrome 7Galactosemia 6,6Optic atrophy, Leber type 6,5Osteogenesis imperfecta 6,5Smith-Lemli-Opitz syndrome 6,5Amyotrophic lateral sclerosis 6Treacher-Collins syndrome 6Tay-Sachs disease 5,75Christ-Siemens-Touraine syndrome 5,5Pheochromocytoma 5,5Retinoblastoma 5,4Rubinstein-Taybi syndrome 5,4Alzheimer disease, familial 5,3Zollinger-Ellison syndrome 5,3Cornelia de Lange syndrome 5,25Familial adenomatous polyposis 5,25Huntington disease 5,25Acromegaly 5Fructose intolerance 5Primary ciliary dyskinesia 5Supranuclear palsy, progressive 5Porphyria, acute intermittent 5Sickle cell anemia 4,8Deletion 5p 4,6Myasthenia gravis 4,55Achondroplasia 4,5Steinert myotonic dystrophy 4,5Ceroid lipofuscinosis, neuronal 4Phenylketonuria 4Smith-Magenis syndrome 4Wilson disease 4Muscular dystrophy limb girdle type 2A, Erb type 3,8CDG syndrome 3,75Niemann-Pick A disease 3,75Propionic acidemia 3,75Waardenburg syndrome type 1, type2 and type 3 3,75Beckwith-Wiedemann syndrome 3,65Adrenoleukodystrophy, X-linked 3,5Goldenhar syndrome 3,5Usher syndrome 3,5Muscular dystrophy, Duchenne and Becker type 3,4Multiple endocrine neoplasia, type 2 3,3

Disease nameEstimated prevalence (/100 000)

Systemic mastocytosisVon Hippel-Lindau diseasePolyarteritis nodosaFriedreich ataxiaPoland anomalyProximal spinal muscular atrophySaethre-Chotzen syndromeWegener granulomatosisKennedy diseaseCystinosisAmaurosis congenita of LeberBOR syndromeBullous pemphigoidKartagener syndromeNiemann-Pick B diseasePseudoxanthoma elasticumLeigh diseasePeutz-Jeghers syndromeAutosomal dominant spinocerebellar ataxiaAlbinism ocularAlport syndromeCrouzon diseaseDeletion 4pKlippel feil syndromeLangerhans cell histiocytosisNail-patella syndromePersistent hyperinsulinemic hypoglycemia of infancyAniridia, sporadicFabry diseaseVariegata porphyriaBudd-Chiari syndromeDarier diseaseX-linked severe combined immunodeficiency, T- B+Bile ducts paucity, syndromic formCat-eye syndromeApert syndromeSpastic paraplegia, familialAdult Onset Still's diseasePierre Robin syndromeGlycogen storage disease type 2Mucopolysaccharidosis type 3Zellweger syndromeNephronophtisis3-hydroxyacyl-CoA dehydrogenase, long chain, deficiency ofAlbers-Schonberg diseaseAngioneurotic edemaAtaxia telangiectasiaChondrodysplasia punctata, rhizomelic typeColoboma, ocularEmery-Dreifuss muscular dystrophy, X-linkedFanconi anemiaGaucher diseaseGorlin syndromeHolt-Oram syndromeHypokaliemic periodic paralysisIsovaleric acidemiaMucopolysaccharidosis type 1Nemaline myopathyNeuroendocrine tumorThomsen and Becker disease

3,33,253,07333332,82,752,52,52,52,52,52,52,252,22,15222222221,751,751,71,51,51,51,41,351,251,251,231,21,11,11,11,0511111111111111111

Estimated prevalence (/100 000)

Churg-Strauss syndromeEllis Van Creveld syndromeJoubert-Boltshauser syndromeBardet-Biedl syndromeEbstein anomalyHyperkaliemic periodic paralysisKrabbe diseaseMucolipidosis type 2Albright hereditary osteodystrophyMenkes syndromeNiemann-Pick C diseaseGlycogen storage disease type 4Alpha-sarcoglycanopathyBeta-sarcoglycanopathyDelta-sarcoglycanopathyGamma-sarcoglycanopathyTetrasomy 18pNeurofibromatosis type 2Xeroderma pigmentosumAgammaglobulinemia X-linkedCowden syndromeWerner syndromeGlutaryl-CoA dehydrogenase deficiency

Homocystinuria due to cystathionine beta-synthase deficiencyMucopolysaccharidosis type 4Lesch-Nyhan syndromePfeiffer syndromeSevere combined immunodeficiency T- B-Anemia congenital hypoplastic, Blackfan-Diamond typeAlkaptonuriaLissencephaly, type 1, due to LIS 1 anomaliesLipodystrophy, Berardinelli typeProgeriaGranulomatous disease, chronicJeune syndromeNanism due to growth hormone resistanceNeurodegeneration with brain iron accumulation (NBIA)Creutzfeldt-Jakob diseaseLowe syndromeMucopolysaccharidosis type 6CHARGE associationMetachromatic leukodystrophyBartter syndromeMuscular dystrophy fukuyama typeWalker-warburg syndromeMuscle eye brain diseaseEwing sarcomaHypercholesterolemia, familial (homozygous form)Fibrodysplasia ossificans progressivaDopa-responsive dystoniaTyrosinemia type 1Factor XIII deficiency, congenitalPerinatal hypophosphatasia

Disease name

0,90,90,850,80,750,750,750,750,720,70,70,60,570,570,570,570,550,50,50,450,450,450,4

0,40,40,380,380,350,320,30,30,250,250,20,20,20,20,190,190,160,140,130,12

0,120,10,10,080,050,050,040,03