{"orpha":357058,"name":"Autosomal recessive cutis laxa type 2A","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["ARCL2A"],"definition":"A rare, genetic, dermis elastic tissue disease characterized by redundant, overfolded skin of variable severity, ranging from wrinkly skin to cutis laxa associated with pre- and post-natal growth retardation, hypotonia, mild to moderate developmental delay, late closure of anterior fontanelle, and craniofacial dysmorphism (including microcephaly, hypertelorism, downslanting palpebral fissures, large, prominent nasal root with funnel nose, small, low-set ears, long philtrum, drooping facial skin). Additional manifestations may include seizures, intellectual disability, congenital hip dislocation, inguinal hernia, and cortical and cerebellar malformations. Pretibial pseudo-ecchymotic skin lesions have occasionally been associated.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-357058/","orphanet_url":"https://www.orpha.net/en/disease/detail/357058","names":{"fr":{"name":"Cutis laxa autosomique récessive type 2A","synonyms":["ARCL2A"],"definition":"Anomalie génétique de l'élasticité du derme rare caractérisée par une peau redondante et plissée, de sévérité variable, allant de la peau ridée à la cutis laxa, associée à un retard de croissance pré- et postnatale, une hypotonie, un retard de développement léger à modéré, fermeture tardive de la fontanelle antérieure et une dysmorphie craniofaciale (microcéphalie, hypertélorisme, fentes palpébrales descendantes, pont nasal large et proéminent et nez en forme d'entonnoir, petites oreilles d'implantation basse, philtrum long, peau du visage relâchée). Les autres manifestations peuvent inclure des convulsions, une déficience intellectuelle, une luxation congénitale de la hanche, une hernie inguinale et des malformations corticales et cérébelleuses. Des lésions cutanées pseudo-ecchymotiques prétibiales ont parfois été associées."},"de":{"name":"Cutis laxa, autosomal-rezessive, Typ 2A","synonyms":["ARCL2A"],"definition":"Eine seltene, genetisch bedingte Erkrankung des elastischen Gewebes der Dermis, die durch eine redundante, übermäßig gefaltete Haut unterschiedlichen Schweregrades gekennzeichnet ist, die von faltiger Haut bis hin zu Cutis Laxa reicht. Sie geht einher mit prä- und postnataler Wachstumsverzögerung, Hypotonie, leichter bis mittlerer Entwicklungsverzögerung, spätem Verschluss der vorderen Fontanelle und Gesichtsdysmorphien (einschließlich Mikrozephalie, Hypertelorismus, schräg abwärts verlaufende Lidspalten, große, vorstehende Nasenwurzel mit Trichternase, kleine, tief angesetzte Ohren, langes Philtrum, hängende Gesichtshaut). Weitere Manifestationen umfassen Krampfanfälle, Intelligenzminderung, angeborene Hüftluxation, Leistenbruch sowie kortikale und zerebelläre Fehlbildungen. Gelegentlich werden pseudoecchymotische Hautläsionen vor dem Schienbein beobachtet."},"es":{"name":"Cutis laxa autosómica recesiva tipo 2A","synonyms":["ARCL2A"],"definition":"Es una enfermedad genética y poco frecuente del tejido elástico de la dermis caracterizada por piel redundante y sobreplegada de gravedad variable, que varía desde piel arrugada a cutis laxa asociada a retraso del crecimiento pre- y postnatal, hipotonía, retraso del desarrollo de leve a moderado, cierre tardío de la fontanela anterior y dismorfia craneofacial (incluyendo microcefalia, hipertelorismo, fisuras palpebrales inclinadas hacia abajo, raíz nasal amplia y prominente con nariz en embudo, orejas de implantación baja, filtrum largo, flacidez facial). Otras manifestaciones adicionales pueden incluir convulsiones, discapacidad intelectual, luxación congénita de cadera, hernia inguinal y malformaciones corticales y cerebelosas. Ocasionalmente se han asociado lesiones cutáneas pseudo-equimóticas pretibiales."},"it":{"name":"Cutis laxa autosomica recessiva tipo 2A","synonyms":["ARCL2A"],"definition":"È una malattia genetica rara del tessuto elastico del derma, caratterizzata da cute ridondante ed aumento della plicatura, di gravità variabile (dalla cute rugosa alla cutis laxa), associata a ritardo della crescita pre- e post-natale, ipotonia, ritardo dello sviluppo lieve-moderato, ritardo nella chiusura della fontanella anteriore e dismorfismi craniofacciali (microcefalia, ipertelorismo, rime palpebrali oblique verso il basso, radice nasale ampia e prominente con naso ad imbuto, orecchie piccole e a basso impianto, filtro lungo e cute del viso cadente). Possono essere presenti crisi epilettiche, disabilità intellettiva, dislocazione congenita dell'anca, ernia inguinale e malformazioni corticali e cerebellari. In rari casi sono state osservate lesioni cutanee pseudo-ecchimotiche pretibiali."},"nl":{"name":"Autosomaal recessieve cutis laxa type 2A","synonyms":["ARCL2A"],"definition":"Een zeldzame, genetische ziekte van het elastisch weefsel van de dermis die gekarakteriseerd wordt door overtollige, overmatig geplooide huid met variabele gradaties va ernst, gaande van gerimpelde huid tot cutis laxa, geassocieerd met pre- en postnatale groeiretardatie, hypotonie, milde tot matige ontwikkelingsachterstand, late sluiting van de voorste fontanel, en craniofaciale dysmorfie (met onder meer microcefalie, hypertelorisme, schuin naar beneden hellende ooglidspleet, grote en opvallende neuswortel met trechterneus, kleine en laagstaande oren, lang filtrum, afhangende gelaatshuid). Mogelijke bijkomende manifestaties zijn onder meer insulten, intellectuele beperking, congenitale dislocatie van de heup, hernia inguinalis (liesbreuk), en malformaties van de cortex en het cerebellum. Pretibiale pseudo-ecchymotische huidlaesies zijn occasioneel geassocieerd."},"pt":{"name":"Cutis laxa autossómica recessiva tipo 2A"},"pl":{"name":"Autosomalna recesywna luźna skóra typu 2A","synonyms":["ARCL2A"]},"cs":{"name":"Autozomálně recesivní cutis laxa, typ 2A","synonyms":["ARCL2A"]},"uk":{"name":"Аутосомно-рецесивний cutis laxa, тип 2A","synonyms":["ARCL2A"],"definition":"A rare, genetic, dermis elastic tissue disease characterized by redundant, overfolded skin of variable severity, ranging from wrinkly skin to cutis laxa associated with pre- and post-natal growth retardation, hypotonia, mild to moderate developmental delay, late closure of anterior fontanelle, and craniofacial dysmorphism (including microcephaly, hypertelorism, downslanting palpebral fissures, large, prominent nasal root with funnel nose, small, low-set ears, long philtrum, drooping facial skin). Additional manifestations may include seizures, intellectual disability, congenital hip dislocation, inguinal hernia, and cortical and cerebellar malformations. Pretibial pseudo-ecchymotic skin lesions have occasionally been associated."},"zh":{"name":"常染色体隐性皮肤松弛2A型","synonyms":["ARCL2A"],"definition":"本病是一种罕见的遗传性真皮弹性组织病，以不同严重程度的多余、折叠皮肤为特征，病变程度可从皮肤皱纹至皮肤松弛。本病还伴有出生前和出生后的生长迟缓、肌张力低下、轻至中度发育迟缓、前囟闭合延迟和颅面畸形(包括小头畸形、眼距过宽、睑裂下斜、大而突出的鼻根和漏斗鼻、小而低的耳朵、长人中及面部皮肤下垂)。本病的其他表现包括癫痫发作、智力障碍、先天性髋关节脱位、腹股沟疝以及皮质和小脑畸形。胫前假性瘀血皮损偶尔也会出现。"},"tr":{"name":"Otozomal resesif kutis laksa tip 2A","synonyms":["ARCL2A"]}},"xrefs":[{"source":"OMIM","code":"219200","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"278250","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q82.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD28.2","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"956396927"},{"source":"MONDO","code":"0018163","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C562632","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0268355","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"1638","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":89826,"name":"Rare skin disease"},"parents":[{"orpha":90350,"name":"Autosomal recessive cutis laxa type 2","classifications":[147,150,156,182,186,187,199]},{"orpha":371071,"name":"Congenital disorder of glycosylation with epilepsy as a major feature","classifications":[156,181]},{"orpha":371200,"name":"Congenital disorder of glycosylation with skin involvement","classifications":[156,187]},{"orpha":371195,"name":"Congenital disorder of glycosylation-related bone disorder","classifications":[147,156]},{"orpha":309778,"name":"Defect in V-ATPase","classifications":[150,156]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[{"orpha":357074,"name":"Autosomal recessive cutis laxa type 2, classic type","type":"Clinical subtype"},{"orpha":2834,"name":"Wrinkly skin syndrome","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"ATP6V0A2","name":"ATPase H+ transporting V0 subunit a2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"18157129[PMID]","hgnc":"18481","ensembl":"ENSG00000185344","omim":"611716","loci":["12q24.31"],"via":{"orpha":2834,"name":"Wrinkly skin syndrome"}},{"symbol":"ATP6V0A2","name":"ATPase H+ transporting V0 subunit a2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"20301755[PMID]_19321599[PMID]_18157129[PMID]","hgnc":"18481","ensembl":"ENSG00000185344","omim":"611716","loci":["12q24.31"],"via":{"orpha":357074,"name":"Autosomal recessive cutis laxa type 2, classic type"}},{"symbol":"ATP6V1A","name":"ATPase H+ transporting V1 subunit A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"28065471[PMID]","hgnc":"851","ensembl":"ENSG00000114573","omim":"607027","loci":["3q13.31"],"via":{"orpha":357074,"name":"Autosomal recessive cutis laxa type 2, classic type"}},{"symbol":"ATP6V1E1","name":"ATPase H+ transporting V1 subunit E1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"28065471[PMID]","hgnc":"857","ensembl":"ENSG00000131100","omim":"108746","loci":["22q11.21"],"via":{"orpha":357074,"name":"Autosomal recessive cutis laxa type 2, classic type"}}],"inheritance":["Autosomal recessive"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":26.0,"area":"Worldwide","status":"Validated","source":"15657616[PMID]_17971833[PMID]_18716235[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"15657616[PMID]_17971833[PMID]_18716235[PMID]_ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-06-23","source":"28294978[PMID]_20301755[PMID]","terms":[{"hpo":"HP:0025082","label":"Abnormal cutaneous elastic fiber morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003160","label":"Abnormal isoelectric focusing of serum transferrin","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007392","label":"Excessive wrinkled skin","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011003","label":"High myopia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004474","label":"Persistent open anterior fontanelle","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0005328","label":"Progeroid facial appearance","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002438","label":"Cerebellar malformation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000270","label":"Delayed cranial suture closure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002198","label":"Dilated fourth ventricle","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005445","label":"Enlarged posterior fossa","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002384","label":"Focal impaired awareness seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002197","label":"Generalized-onset seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000023","label":"Inguinal hernia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001302","label":"Pachygyria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001763","label":"Pes planus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008897","label":"Postnatal growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011451","label":"Primary microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000426","label":"Prominent nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005272","label":"Prominent nasolabial fold","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005484","label":"Secondary microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011344","label":"Severe global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006891","label":"Thick cerebral cortex","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100874","label":"Thick hair","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000260","label":"Wide anterior fontanel","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001892","label":"Abnormal bleeding","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002334","label":"Abnormality of the cerebellar vermis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002305","label":"Athetosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000592","label":"Blue sclerae","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001320","label":"Cerebellar vermis hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001374","label":"Congenital hip dislocation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001305","label":"Dandy-Walker malformation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006989","label":"Dysplastic corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002007","label":"Frontal bossing","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001350","label":"Slurred speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000481","label":"Abnormal cornea morphology","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002659","label":"Increased susceptibility to fractures","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0007957","label":"Corneal opacity","frequency":"Excluded (0%)","criteria":null},{"hpo":"HP:0000974","label":"Hyperextensible skin","frequency":"Excluded (0%)","criteria":null}]}}