{"orpha":370968,"name":"Congenital muscular dystrophy with intellectual disability","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["CMD with intellectual disability","CMD-MR"],"definition":"A rare, genetic, congenital muscular dystrophy due to dystroglycanopathy disorder characterized by a wide phenotypic spectrum which includes hypotonia and muscular weakness present at birth or early infancy and delayed or arrested motor development, associated with mild to severe intellectual disability and variable brain abnormalities on neuroimaging studies. Feeding difficulties, joint and spinal deformities, respiratory insufficiency, and ocular anomalies (e.g. strabismus, retinal dystrophy, oculomotor apraxia) may be associated. Decreased or absent alpha-dystroglycan on immunohistochemical muscle staining and elevated serum creatine kinase are observed.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-370968/","orphanet_url":"https://www.orpha.net/en/disease/detail/370968","names":{"fr":{"name":"Dystrophie musculaire congénitale avec déficience intellectuelle","synonyms":["CMD avec déficience intellectuelle","CMD-MR","DMC avec déficience intellectuelle"],"definition":"Dystrophie musculaire congénitale rare d'origine génétique, due à une dystroglycanopathie caractérisée par un large spectre phénotypique comprenant une hypotonie et une faiblesse musculaire présentes à la naissance ou survenant dans la petite enfance et un retard ou un arrêt du développement moteur, associés à une déficience intellectuelle légère à sévère et à des anomalies cérébrales variables détectées par neuro-imagerie. Des difficultés à s'alimenter, des déformations des articulations et de la colonne vertébrale, une insuffisance respiratoire et des anomalies oculaires (strabisme, dystrophie rétinienne, apraxie oculomotrice) peuvent être associées. Une diminution ou une absence d'alpha-dystroglycane à la coloration immunohistochimique de la biopsie musculaire et une élévation de la créatine kinase sérique sont observées."},"de":{"name":"Kongenitale Muskeldystrophie mit Intelligenzminderung","synonyms":["CMD mit Intelligenzminderung","CMD-MR"],"definition":"Die Kongenitale Muskeldystrophie mit Intelligenzminderung ist eine seltene, genetische, angeborene Muskeldystrophie aufgrund einer Dystroglykanopathie. Die Krankheit ist durch ein breites phänotypisches Spektrum gekennzeichnet, das mit Hypotonie und Muskelschwäche bei der Geburt oder im frühen Kindesalter sowie einer verzögerten oder blockierten motorischen Entwicklung einhergeht, verbunden mit einer leichten bis schweren geistigen Behinderung und variablen Hirnanomalien, die sich in der Bildgebung des zentralen Nervensystems darstellen. Ernährungsschwierigkeiten, Gelenk- und Wirbelsäulendeformitäten, Ateminsuffizienz und okuläre Anomalien (z.B. Schielen, Netzhautdystrophie, okulomotorische Apraxie) können assoziiert sein. Verminderte oder fehlende Alpha-Dystroglykane bei immunhistochemischer Muskelfärbung und erhöhte Serum-Kreatinkinase werden beobachtet."},"es":{"name":"Distrofia muscular congénita con discapacidad intelectual","synonyms":["DMC con discapacidad intelectual"],"definition":"Es una distrofia muscular congénita por distroglicanopatía, genética y poco frecuente. Está caracterizada por un amplio espectro fenotípico que incluye hipotonía y debilidad muscular presente al nacimiento o en la infancia temprana y retraso o detención del desarrollo motor asociado con discapacidad intelectual de leve a grave, y hallazgo de anomalías cerebrales variables en estudios de neuroimagen. También se pueden asociar dificultades en la alimentación, malformaciones articulares y espinales, insuficiencia respiratoria y anomalías oculares (p. ej., estrabismo, distrofia retiniana, apraxia oculomotora). Se observa disminución o ausencia de alfa-distroglicano en la tinción inmunohistoquímica de biopsias musculares y aumento de la creatinquinasa sérica."},"it":{"name":"Distrofia muscolare congenita con disabilità intellettiva","synonyms":["CMD con deficit cognitivo","CMD-MR"],"definition":"La distrofia muscolare congenita con disabilità intellettiva è una distrofia muscolare congenita genetica rara, causata da una distroglicanopatia, che presenta un quadro clinico eterogeneo, con ipotonia e debolezza muscolare congenite o ad esordio neonatale, e arresto o ritardo dello sviluppo motorio, associati a disabilità intellettiva da lieve a grave ed anomalie cerebrali di grado variabile evidenti alle neuroimmagini. Possono associarsi difficoltà di alimentazione, deformità articolari e della colonna, insufficienza respiratoria ed anomalie oculari (ad es. strabismo, distrofia retinica, aprassia oculomotoria). La colorazione immunoistochimica dei muscoli evidenzia una riduzione o l'assenza di alfa-distroglicano. I livelli di creatin-chinasi nel siero sono aumentati."},"nl":{"name":"Congenitale spierdystrofie met intellectuele achterstand","synonyms":["CMD-MR","CMD met intellectuele achterstand"],"definition":"Congenitale spierdystrofie met intellectuele achterstand is een zeldzame, genetische, congenitale musculaire dystrofie als gevolg van dystroglycanopathie, en wordt gekarakteriseerd door een breed fenotypisch spectrum met onder meer hypotonie spierzwakte present bij de geboorte of in de vroege zuigelingentijd en vertraagde of onderbroken motorische ontwikkeling, geassocieerd met milde tot ernstige intellectuele achterstand en variabele afwijkingen van de hersenen bij neurologische beeldvormingsonderzoeken. Voedingsproblemen, misvormingen van gewrichten en ruggenmerg, respiratoire insufficiëntie, en oculaire anomalieën (e.g. strabisme, retinadystrofie, oculomotorische apraxie) kunnen geassocieerd zijn. Bij immunohistochemische kleuring van spierweefsel wordt een verminderde hoeveelheid of afwezigheid van alfa-dystroglycan waargenomen, en het gehalte van creatinekinase in het serum is verhoogd."},"pt":{"name":"Distrofia muscular congénita com perturbação do desenvolvimento intelectual","synonyms":["CMD com perturbação do desenvolvimento intelectual","CMD-MR"]},"pl":{"name":"Wrodzona dystrofia mięśniowa z niepełnosprawnością intelektualną","synonyms":["CMD z niepełnosprawnością intelektualną","CMD-MR"],"definition":"*Wrodzona dystrofia mięśniowa z niepełnosprawnością intelektualną jest rzadką, genetycznie uwarunkowaną, wrodzoną dystrofią mięśniową o typie dystroglikanopatii, która charakteryzuje się szerokim spektrum objawów klinicznych i obejmuje hipotonię i osłabienie mięśni, występujące od urodzenia lub pojawiające się we wczesnym dzieciństwie, oraz opóźnienie lub zahamowanie rozwoju ruchowego, z towarzyszącą niepełnosprawnością intelektualną w stopniu łagodnym lub znacznym oraz różne nieprawidłowości mózgu widoczne w badaniach neuroobrazowych. Mogą wystąpić trudności w karmieniu, deformacje stawów i kręgosłupa, niewydolność oddechowa i wady oczu (np. zez, dystrofia siatkówki, apraksja okoruchowa). W badaniu immunohistochemicznym mięśni stwierdza się obniżenie ekspresji lub brak alfa-dystroglikanu, a w badaniach biochemicznych podwyższoną aktywność kinazy kreatynowej w surowicy krwi."},"cs":{"name":"Vrozená svalová dystrofie s mentální retardací","synonyms":["CMD s mentální retardací","CMD-MR"]},"uk":{"name":"Вроджена мязова дистрофія з інтелектуальною недостатністю","synonyms":["ВМД з інтелектуальною недостатністю","CMD-MR"],"definition":"A rare, genetic, congenital muscular dystrophy due to dystroglycanopathy disorder characterized by a wide phenotypic spectrum which includes hypotonia and muscular weakness present at birth or early infancy and delayed or arrested motor development, associated with mild to severe intellectual disability and variable brain abnormalities on neuroimaging studies. Feeding difficulties, joint and spinal deformities, respiratory insufficiency, and ocular anomalies (e.g. strabismus, retinal dystrophy, oculomotor apraxia) may be associated. Decreased or absent alpha-dystroglycan on immunohistochemical muscle staining and elevated serum creatine kinase are observed."},"zh":{"name":"先天性肌营养不良伴智力障碍","synonyms":["CMD伴智力障碍"],"definition":"先天性肌营养不良伴智力障碍是一种由抗萎缩相关糖蛋白病所引起的罕见遗传性先天性肌营养不良症，本病的特征是表型谱广，包括出生或早期出现的肌张力低和肌无力，运动发育迟缓或停滞，并伴有轻至重度的智力障碍和神经影像学检查中的各种脑异常。喂养困难、关节和脊柱畸形、呼吸功能不全和眼部异常(如斜视、视网膜营养不良、动眼失用症)可能与此有关。免疫组织化学肌肉染色显示α-抗萎缩相关蛋白减少或缺失，且血清肌酸激酶升高。"},"tr":{"name":"Zihinsel yetersizlik ile seyreden doğumsal kas distrofisi","synonyms":["CMD-MR","Zihinsel yetersizlik ile seyreden CMD"]}},"xrefs":[{"source":"OMIM","code":"606612","qualifier":"NTBT","icd_relation":null,"validated":true},{"source":"OMIM","code":"608840","qualifier":"NTBT","icd_relation":null,"validated":true},{"source":"OMIM","code":"613155","qualifier":"NTBT","icd_relation":null,"validated":true},{"source":"OMIM","code":"613156","qualifier":"NTBT","icd_relation":null,"validated":true},{"source":"OMIM","code":"615351","qualifier":"NTBT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618992","qualifier":"NTBT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G71.2","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C54.1","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0018278","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5190846","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":371047,"name":"Congenital disorder of glycosylation with neurological involvement","classifications":[156,181]},{"orpha":370953,"name":"Congenital muscular dystrophy due to dystroglycanopathy","classifications":[156,181]},{"orpha":309469,"name":"Disorder of O-mannosylglycan synthesis","classifications":[150,156]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"FKRP","name":"fukutin related protein","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21397493[PMID]","hgnc":"17997","ensembl":"ENSG00000181027","omim":"606596","loci":["19q13.32"]},{"symbol":"GMPPB","name":"GDP-mannose pyrophosphorylase B","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23768512[PMID]_21397493[PMID]","hgnc":"22932","ensembl":"ENSG00000173540","omim":"615320","loci":["3p21.31"]},{"symbol":"LARGE1","name":"LARGE xylosyl- and glucuronyltransferase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21397493[PMID]","hgnc":"6511","ensembl":"ENSG00000133424","omim":"603590","loci":["22q12.3"]},{"symbol":"POMT1","name":"protein O-mannosyltransferase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21397493[PMID]","hgnc":"9202","ensembl":"ENSG00000130714","omim":"607423","loci":["9q34.13"]},{"symbol":"POMT2","name":"protein O-mannosyltransferase 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21397493[PMID]","hgnc":"19743","ensembl":"ENSG00000009830","omim":"607439","loci":["14q24.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Not yet documented","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"},{"type":"Annual incidence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-04-26","source":"30454682[PMID]_19299310[PMID]_17878207[PMID]_17634419[PMID]_20301468[PMID]","terms":[{"hpo":"HP:0003236","label":"Elevated circulating creatine kinase concentration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008947","label":"Floppy infant","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0030046","label":"Hypoglycosylation of alpha-dystroglycan","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0030099","label":"Reduced muscle fiber alpha dystroglycan","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008981","label":"Calf muscle hypertrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030197","label":"Fatigable weakness of skeletal muscles","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003325","label":"Limb-girdle muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002828","label":"Multiple joint contractures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007015","label":"Poor gross motor coordination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002518","label":"Abnormal periventricular white matter morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003549","label":"Abnormality of connective tissue","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000478","label":"Abnormality of the eye","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000707","label":"Abnormality of the nervous system","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007361","label":"Abnormality of the pons","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0040173","label":"Abnormality of the tongue muscle","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003327","label":"Axial muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001320","label":"Cerebellar vermis hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004637","label":"Decreased cervical spine mobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010628","label":"Facial palsy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002827","label":"Hip dislocation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002505","label":"Loss of ambulation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000054","label":"Micropenis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000580","label":"Pigmentary retinopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001315","label":"Reduced tendon reflexes","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002878","label":"Respiratory failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002093","label":"Respiratory insufficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003712","label":"Skeletal muscle hypertrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008443","label":"Spinal deformities","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null}]}}