{"orpha":83629,"name":"Leukoencephalopathy-spondyloepimetaphyseal dysplasia syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["H-SMD","Hypomyelination-spondyloepimetaphyseal dysplasia syndrome","Leukoencephalopathy-SEMD syndrome","Leukoencephalopathy-metaphyseal chondrodysplasia syndrome"],"definition":"A rare genetic neurological disorder characterized by the association of hypomyelinating leukodystrophy with spondylometaphyseal dysplasia. Patients present in infancy with absent or delayed ability to walk independently, slowly progressive motor deterioration, spasticity, ataxia, proximal weakness, and joint contractures. Additional manifestations include mild cognitive impairment, short stature, scoliosis, enlarged and deformed joints, dysarthria, nystagmus, visual defects, and mildly dysmorphic features, among others. Mode of inheritance is X-linked recessive.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-83629/","orphanet_url":"https://www.orpha.net/en/disease/detail/83629","names":{"fr":{"name":"Syndrome de leucoencéphalopathie-dysplasie spondylo-épimétaphysaire","synonyms":["H-SMD","Syndrome d'hypomyélinisation-dysplasie spondylo-métaphysaire","Syndrome de leucoencéphalopathie-SEMD","Syndrome de leucoencéphalopathie-chondrodysplasie métaphysaire"],"definition":"Maladie neurologique rare, d'origine génétique, caractérisée par l'association d'une leucodystrophie hypomyélinisante avec une dysplasie spondylo-métaphysaire. Au cours de la petite enfance, les patients présentent une absence ou un retard d'acquisition de la marche autonome, une lente détérioration des fonctions motrices, une spasticité, une ataxie, une faiblesse proximale et des contractures articulaires. Parmi les autres manifestations figurent un léger trouble cognitif, une petite taille, une scoliose, une déformation et une hypertrophie des articulations, une dysarthrie, un nystagmus, des défauts visuels et une légère dysmorphie, entre autres. Le mode de transmission est récessif et lié à l'X."},"de":{"name":"Leukoenzephalopathie-spondylometaphysäre Dysplasie-Syndrom","synonyms":["H-SMD","Hypomyelinisierung-spondyloepimetaphysäre Dysplasie-Syndrom","Leukenzephalopathie-SEMD-Syndrom","Leukoenzephalopathie-spondylometaphysäre Chondrodysplasie-Syndrom"],"definition":"Eine seltene genetisch bedingte neurologische Störung, bei der eine hypomyelinisierende Leukodystrophie mit einer spondylometaphysären Dysplasie einhergeht. Die Betroffenen zeigen im Säuglingsalter eine fehlende oder verzögerte Fähigkeit, unabhängig zu gehen, eine langsam fortschreitende motorische Verschlechterung, Spastizität, Ataxie, proximale Schwäche und Gelenkkontrakturen. Zu den weiteren Symptomen gehören leichte kognitive Beeinträchtigungen, Kleinwuchs, Skoliose, vergrößerte und deformierte Gelenke, Dysarthrie, Nystagmus, Sehstörungen und leichte Dysmorphien. Der Vererbungsmodus ist X-chromosomal-rezessiv."},"es":{"name":"Síndrome de leucoencefalopatía-displasia espondiloepimetafisaria","synonyms":["Síndrome de hipomielinización-displasia espondiloepimetafisaria","Síndrome de leucoencefalopatía-condrodisplasia metafisaria"],"definition":"Es un trastorno neurológico de origen genético y poco frecuente caracterizado por la asociación de leucodistrofia hipomielinizante y displasia espondilometafisaria. Los pacientes se presentan en la infancia con incapacidad o retraso de la deambulación independiente, deterioro motor lentamente progresivo, espasticidad, ataxia, debilidad proximal y contracturas articulares. Otras manifestaciones adicionales incluyen leve deterioro cognitivo, talla baja, escoliosis, articulaciones ensanchadas y deformadas, disartria, nistagmo, defectos visuales y características levemente dismórficas, entre otras. El modo de herencia es recesivo ligado al cromosoma X."},"it":{"name":"Sindrome leucoencefalopatia -displasia spondilometafisaria","definition":"Si tratta di una malattia neurologica genetica rara, caratterizzata da leucodistrofia ipomielinizzante associata a displasia spondilometafisaria. Nella prima infanzia, i pazienti presentano assenza o ritardo della deambulazione autonoma, deterioramento motorio a progressione lenta, spasticità, atassia, debolezza prossimale e contratture articolari. Altri segni clinici sono il lieve deficit cognitivo, la bassa statura, la scoliosi, le articolazioni larghe e deformi, la disartria, il nistagmo, i difetti della vista e i dismorfismi sfumati. La trasmissione è recessiva legata all'X."},"nl":{"name":"Leuko-encefalopathie - spondylo-epimetafysaire dysplasie-syndroom","synonyms":["H-SMD","Hypomyelinisatie - spondylo-epimetafysaire dysplasie-syndroom","Leuko-encefalopathie - SEMD-syndroom","Leuko-encefalopathie - metafysaire chondrodysplasie-syndroom"],"definition":"Een zeldzame, genetische neurologische aandoening, gekarakteriseerd door de associatie van hypomyeliniserende leukodystrofie met spondylometafysaire dysplasie. Patiënten presenteren zich in de zuigelingentijd met afwezig of vertraagd vermogen om onafhankelijk te lopen, traag progressieve motorische aftakeling, spasticiteit, ataxie, proximale zwakte, en gewrichtscontracturen. Bijkomende manifestaties zijn onder meer milde cognitieve functiestoornis, kleine gestalte, scoliose, vergrote en misvormde gewrichten, dysartrie, nystagmus, visuele defecten, en milde dysmorfe kenmerken. Overerving gebeurt X-gebonden recessief."},"pt":{"name":"Síndrome de leucoencefalopatia-displasia espondiloepimetafisária","synonyms":["H-SMD","Síndrome de hipomielinização-displasia espondiloepimetafisária","Síndrome de leucoencefalopatia-SEMD","Síndrome de leucoencefalopatia-condrodisplasia metafisária"]},"pl":{"name":"Leukoencefalopatia - chondrodysplazja przynasadowa","synonyms":["H-SMD","Hypomyelination-spondyloepimetaphyseal dysplasia syndrome","Leukoencephalopathy-SEMD syndrome","Leukoencephalopathy-metaphyseal chondrodysplasia syndrome"]},"cs":{"name":"Syndrom zahrnující leukoencefalopatii a metafyzární chondrodysplázii","synonyms":["H-SMD","Hypomyelination-spondyloepimetaphyseal dysplasia syndrome","Leukoencephalopathy-SEMD syndrome","Leukoencephalopathy-metaphyseal chondrodysplasia syndrome"]},"uk":{"name":"Синдром лейкоенцефалопатії-спондилоепіметафізарної дисплазії","synonyms":["H-SMD","Синдром гіпомієлінізації-спондилоепіметафізарної дисплазії","Синдром лейкоенцефалопатії-метафізарної хондродисплазії","Синдром лейкоенцефалопатії-SEMD"],"definition":"A rare genetic neurological disorder characterized by the association of hypomyelinating leukodystrophy with spondylometaphyseal dysplasia. Patients present in infancy with absent or delayed ability to walk independently, slowly progressive motor deterioration, spasticity, ataxia, proximal weakness, and joint contractures. Additional manifestations include mild cognitive impairment, short stature, scoliosis, enlarged and deformed joints, dysarthria, nystagmus, visual defects, and mildly dysmorphic features, among others. Mode of inheritance is X-linked recessive."},"zh":{"name":"脑白质病-脊柱干骺端发育不良综合征","synonyms":["脑白质病-干骺端软骨发育异常综合征"]},"tr":{"name":"Lökoensefalopati-spondilometafizyel displazi sendromu","synonyms":["H-SMD","Hipomiyelinizasyon-spondilometafizyal displazi sendromu","Lökoensefalopati-metafizyal kondrodisplazi sendromu"]}},"xrefs":[{"source":"OMIM","code":"300232","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G37.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0010275","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4304743","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"4891","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[{"type":"Moved to","orpha":168448,"name":"Spondyloepimetaphyseal dysplasia, Bieganski type","status":"inactive"}],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":183500,"name":"Genetic neurodegenerative disease","classifications":[156]},{"orpha":68356,"name":"Leukodystrophy","classifications":[156,181]},{"orpha":182070,"name":"Rare neurodegenerative disease","classifications":[181]},{"orpha":253,"name":"Spondyloepiphyseal dysplasia and spondyloepimetaphyseal dysplasia","classifications":[147,156,199]}],"children":[],"genes":[{"symbol":"AIFM1","name":"apoptosis inducing factor mitochondria associated 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"27102849[PMID]","hgnc":"8768","ensembl":"ENSG00000156709","omim":"300169","loci":["Xq26.1"]}],"genes_via_subtypes":[],"inheritance":["X-linked recessive"],"onset":["Childhood","Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":11.0,"area":"Worldwide","status":"Validated","source":"16924009[PMID]_10486082[PMID]_27102849[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_16924009[PMID]_10486082[PMID]_27102849[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2018-02-05","source":"16924009[PMID]","terms":[{"hpo":"HP:0002352","label":"Leukoencephalopathy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0005871","label":"Metaphyseal chondrodysplasia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0100707","label":"Abnormal astrocyte morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012747","label":"Abnormal brainstem MRI signal intensity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000587","label":"Abnormal optic nerve morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003487","label":"Babinski sign","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003020","label":"Enlargement of the wrists","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030866","label":"Large knee","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002062","label":"Morphological abnormality of the pyramidal tract","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004349","label":"Reduced bone mineral density","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001258","label":"Spastic paraplegia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030051","label":"Tip-toe gait","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001337","label":"Tremor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000505","label":"Visual impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005280","label":"Depressed nasal bridge","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000666","label":"Horizontal nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011800","label":"Midface retrusion","frequency":"Occasional (29-5%)","criteria":null}]}}