{"orpha":2505,"name":"Multiple benign circumferential skin creases on limbs","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["CCSF","Circumferential skin creases, Kunze type","Congenital circumferential skin folds","Kunze-Riehm syndrome"],"definition":"A rare genetic disease characterized by benign circumferential skin creases, mainly on the limbs, due to folding of excess skin. The creases often improve spontaneously in childhood. Patients also exhibit variable degrees of intellectual disability, short stature, cleft palate, and facial dysmorphism (including epicanthal folds, microphthalmia, broad nasal bridge, low-set, posteriorly rotated ears, and microstomia, among others). Variable additional features have been reported, such as seizures, infantile hypotonia, hearing impairment, strabismus, and urogenital anomalies. Brain imaging may show hypoplastic corpus callosum or mildly dilated ventricles.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-2505/","orphanet_url":"https://www.orpha.net/en/disease/detail/2505","names":{"fr":{"name":"Plis circulaires bénins multiples de la peau des membres","synonyms":["CCSF","Plis circonférentiels congénitaux de la peau","Syndrome de Kunze-Riehm"],"definition":"Maladie génétique rare caractérisée par des plis cutanés circonférentiels bénins, principalement sur les membres, dus à des plis formés par un excès de peau. Les plis s'améliorent souvent spontanément dans l'enfance. Les patients présentent également des degrés variables de déficience intellectuelle, une petite taille, une fente palatine et une dysmorphie faciale (y compris, entre autres, des plis épicanthaux, une microphtalmie, un large pont nasal, des oreilles implantées bas, orientées vers l'arrière et une microstomie). D'autres caractéristiques variables ont été rapportées, telles que des crises d'épilepsie, une hypotonie infantile, une déficience auditive, un strabisme et des anomalies urogénitales. L'imagerie cérébrale peut mettre en évidence un corps calleux hypoplasique ou des ventricules légèrement dilatés."},"de":{"name":"Multiple benigne ringförmige Hautfalten der Extremitäten","synonyms":["CCSF","Hautfalten, ringförmige, Typ Kunze","Kongenitale ringförmige Hautfalten","Kunze-Riehm-Syndrom"],"definition":"Eine seltene genetische Erkrankung, die durch gutartige, umlaufende Hautfalten, vor allem an den Extremitäten, gekennzeichnet ist, die durch Faltenbildung überschüssiger Haut entstehen. Die Falten bilden sich oft spontan in der Kindheit zurück. Die Patienten weisen einen unterschiedlichen Grad an Intelligenzminderung, Kleinwuchs, Gaumenspalte und Gesichtsdysmorphien auf (einschließlich Epikanthusfalten, Mikrophthalmie, breiter Nasenrücken, tiefsitzende, nach hinten gedrehte Ohren und Mikrostomie). Es wurde über verschiedene zusätzliche Merkmale berichtet, z. B. Krampfanfälle, infantile Hypotonie, Hörstörungen, Schielen und urogenitale Anomalien. Die zerebrale Bildgebung kann ein hypoplastisches Corpus callosum oder leicht erweiterte Ventrikel zeigen."},"es":{"name":"Pliegues circulares benignos múltiples de la piel de las extremidades","synonyms":["CCSF","Pliegues circulares de la piel congénitos","Pliegues circulares de la piel tipo Kunze","Síndrome de Kunze-Riehm"],"definition":"Es una enfermedad de base genética poco frecuente caracterizada por unos pliegues cutáneos circunferenciales benignos, principalmente en las extremidades, debido al plegamiento del exceso de piel. Los pliegues suelen mejorar de forma espontánea en la infancia. Los pacientes también exhiben grados variables de discapacidad intelectual, talla baja, hendidura palatina y dismorfia facial (incluidos pliegues epicánticos, microftalmía, puente nasal ancho, orejas de baja implantación rotadas posteriormente y microstomía, entre otros). También se han descrito otras características adicionales variables, como crisis epilépticas, hipotonía en lactantes, discapacidad auditiva, estrabismo y anomalías urogenitales. Las neuroimágenes pueden mostrar hipoplasia del cuerpo calloso o una ligera dilatación ventricular."},"it":{"name":"Pliche cutanee circonferenziali benigne multiple sugli arti","synonyms":["CCSF","MTBS","Pieghe cutanee circonferenziali congenite","Sindrome del bambino Michelin","Sindrome di Kunze-Riehm"],"definition":"Si tratta di una malattia genetica rara, caratterizzata da pliche cutanee benigne, disposte per lo più lungo la circonferenza degli arti, secondarie al ripiegamento della cute ridondante. Spesso le pliche migliorano spontaneamente durante l'infanzia. I pazienti presentano anche disabilità intellettiva di gravità variabile, bassa statura, palatoschisi e dismorfismi facciali (epicanto, microftalmia, sella nasale ampia, orecchie a basso impianto ruotate posteriormente e microstomia). I pazienti possono presentare anche crisi epilettiche, ipotonia infantile, compromissione dell'udito, strabismo e anomalie urogenitali. Le neuroimmagini mostrano l'ipoplasia del corpo calloso o ventricoli leggermente dilatati."},"nl":{"name":"Meervoudige goedaardige circumferentiële huidplooien op ledematen","synonyms":["CCSF","Circumferentiële huidplooien, Kunze-type","Congenitale circumferentiële huidplooien","Syndroom van Kunze-Riehm"],"definition":"Een zeldzame, genetische aandoening, gekarakteriseerd door goedaardige circumferentiële huidplooien, voornamelijk gesitueerd op ledematen, als gevolg van plooiing van overtollige huid. De plooien verbeteren vaak spontaan in de kindertijd. Patiënten vertonen ook variabele gradaties van intellectuele achterstand, kleine gestalte, gespleten verhemelte, en faciale dysmorfie (met onder meer epicanthusplooien, microftalmie, brede neusbrug, laagstaande en naar achteren gedraaide oren, en microstomie). Er werden bijkomende variabele kenmerken gerapporteerd, waaronder insulten, infantiele hypotonie, gehoorverlies, strabisme, en urogenitale anomalieën. Beeldvorming van hersenen toont mogelijk hypoplastisch corpus callosum of mild gedilateerde ventrikels."},"pt":{"name":"Pregas cutâneas circunferenciais benignas múltiplas dos membros","synonyms":["Pregas cutâneas circunferenciais congénitas","Pregas cutâneas circunferenciais, tipo Kunze","Síndrome Kunze-Riehm","Síndrome bebé Michelin"]},"pl":{"name":"Mnogie łagodne bruzdy-obręcze na kończynach","synonyms":["CCSF","Zespół Kunze'a i Riehma","Wrodzone obwodowe fałdy skórne"]},"cs":{"name":"Mnohočetné benigní obvodové rýhy na končetinách","synonyms":["CCSF","MTBS","Vrozené obvodové záhyby kůže","Kunzeho-Riehmův syndrom","Syndrom dítěte podobného pneumatice Michelin","Kunze-Riehmův syndrom"]},"uk":{"name":"Множинні доброякісні окружні складки шкіри на кінцівках","synonyms":["CCSF","Циркулярні складки шкіри, тип Кунце","Вроджені циркулярні складки шкіри","Синдром Кунце-Ріма"],"definition":"A rare genetic disease characterized by benign circumferential skin creases, mainly on the limbs, due to folding of excess skin. The creases often improve spontaneously in childhood. Patients also exhibit variable degrees of intellectual disability, short stature, cleft palate, and facial dysmorphism (including epicanthal folds, microphthalmia, broad nasal bridge, low-set, posteriorly rotated ears, and microstomia, among others). Variable additional features have been reported, such as seizures, infantile hypotonia, hearing impairment, strabismus, and urogenital anomalies. Brain imaging may show hypoplastic corpus callosum or mildly dilated ventricles."},"zh":{"name":"四肢多发性良性圆周形皮纹","synonyms":["环形皮肤皱襞，Kunze型"]},"tr":{"name":"Ekstremitelerde çoklu selim çevresel cilt kırışıklıkları","synonyms":["CCSF","Kunze-Riehm sendromu","Doğumsal çevresel deri kıvrımları","Çevresel cilt kırışıklıkları, Kunze tipi"]}},"xrefs":[{"source":"OMIM","code":"156610","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"616734","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q82.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD2F.1Y","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0007990","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C537575","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0473586","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"3589","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":89826,"name":"Rare skin disease"},"parents":[{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]},{"orpha":79385,"name":"Unclassified genetic skin disorder","classifications":[156,187]}],"children":[],"genes":[{"symbol":"MAPRE2","name":"microtubule associated protein RP/EB family member 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"26637975[PMID]","hgnc":"6891","ensembl":"ENSG00000166974","omim":"605789","loci":["18q12.1-q12.2"]},{"symbol":"TUBB","name":"tubulin beta class I","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"26637975[PMID]","hgnc":"20778","ensembl":"ENSG00000196230","omim":"191130","loci":["6p21.33"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant","Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":32.0,"area":"Worldwide","status":"Validated","source":"29696100[PMID]_39583440[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"29696100[PMID]_39583440[PMID]_ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2016-06-01","source":null,"terms":[{"hpo":"HP:0000969","label":"Edema","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007522","label":"Increased number of skin folds","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001072","label":"Thickened skin","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000175","label":"Cleft palate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007400","label":"Irregular hyperpigmentation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000377","label":"Abnormal pinna morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000271","label":"Abnormality of the face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003011","label":"Abnormality of the musculature","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000045","label":"Abnormality of the scrotum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001635","label":"Congestive heart failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002230","label":"Generalized hirsutism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000047","label":"Hypospadias","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000023","label":"Inguinal hernia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006768","label":"Localized neuroblastoma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100559","label":"Lower limb asymmetry","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000482","label":"Microcornea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000568","label":"Microphthalmia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000488","label":"Retinopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000046","label":"Small scrotum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001537","label":"Umbilical hernia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100560","label":"Upper limb asymmetry","frequency":"Occasional (29-5%)","criteria":null}]}}