{"orpha":562528,"name":"Congenital limbs-face contractures-hypotonia-developmental delay syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["CLIFAHDD syndrome"],"definition":"A rare multiple congenital anomalies/dysmorphic syndrome with intellectual disability characterized by severe congenital contractures of the limbs and face, hypotonia, neonatal respiratory distress, and global developmental delay. Dysmorphic facial features include downslanting palpebral fissures, broad nasal bridge, large nares, long philtrum, and deep nasolabial folds, among others. Limb deformities (camptodactyly, clubfoot), short neck, scoliosis, as well as seizures have also been reported. Brain MRI may show cerebral and cerebellar atrophy in some cases.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-562528/","orphanet_url":"https://www.orpha.net/en/disease/detail/562528","names":{"fr":{"name":"Syndrome de contractures congénitales des membres et de la face-hypotonie-retard de développement","synonyms":["Syndrome CLIFAHDD"],"definition":"Anomalies congénitales multiples/syndrome dysmorphique rare avec déficience intellectuelle caractérisé par des contractures congénitales sévères des membres et du visage, une hypotonie, une détresse respiratoire néonatale et un retard global de développement. La dysmorphie faciale inclut des fentes palpébrales inclinées vers le bas, un large pont nasal de larges narines, un long philtrum et des plis nasolabiaux marqués. Des déformations des membres (camptodactylie, pied bot), un cou court, une scoliose, ainsi que des crises convulsives ont également été rapportés. Dans certains cas, l'IRM cérébrale peut révéler une atrophie cérébrale et cérébelleuse."},"de":{"name":"Kongenitale Extremitäten- und Gesichtskontrakturen-Hypotonie-Entwicklungsverzögerung-Syndrom","synonyms":["CLIFAHDD-Syndrom"],"definition":"Ein seltenes Syndrom mit multiplen kongenitalen Anomalien und Intelligenzminderung, das durch schwere angeborene Kontrakturen der Gliedmaßen und des Gesichts, Hypotonie, neonatale Atemnot und eine globale Entwicklungsverzögerung gekennzeichnet ist. Zu den Gesichtsdysmorphien gehören u. a. schräg abwärts verlaufende Lidspalten, ein breiter Nasenrücken, große Nasenlöcher, ein langes Philtrum und tiefe Nasolabialfalten. Es wurde auch über Fehlbildungen der Gliedmaßen (Kamptodaktylie, Klumpfuß), einen kurzen Hals, Skoliose und Krampfanfälle berichtet. Die MRT des Gehirns kann in einigen Fällen eine zerebrale und zerebellare Atrophie zeigen."},"es":{"name":"Síndrome de contracturas congénitas faciales y de las extremidades-hipotonía-retraso del desarrollo","synonyms":["Síndrome CLIFAHDD"],"definition":"Es un síndrome dismórfico/ de múltiples anomalías congénitas poco frecuente con discapacidad intelectual caracterizado por graves contracturas congénitas de las extremidades y la cara, hipotonía, dificultad respiratoria neonatal y retraso global del desarrollo. Las características faciales dismórficas incluyen fisuras palpebrales descendentes, puente nasal ancho, narinas amplias, surco nasolabial largo y pliegues nasolabiales profundos, entre otros. También se han descrito deformidades de las extremidades (camptodactilia, pie zambo), cuello corto y escoliosis, así como crisis. La neuroimagen puede mostrar atrofia cerebral y cerebelosa en algunos casos."},"it":{"name":"Sindrome contratture congenite degli arti e del viso-ipotonia-ritardo dello sviluppo","synonyms":["Sindrome CLIFAHDD"],"definition":"Si tratta di una malattia rara da anomalie/dismorfismi congeniti multipli associata a disabilità intellettiva, caratterizzata da gravi contratture congenite degli arti e del viso, ipotonia, distress respiratorio neonatale e ritardo dello sviluppo globale. I dismorfismi facciali comprendono le rime palpebrali oblique verso il basso, la sella nasale larga, le narici grandi, il filtro lungo e le pliche nasolabiali profonde. I pazienti possono presentare anche deformità degli arti (camptodattilia, piede torto), collo corto, scoliosi e crisi epilettiche. In alcuni pazienti, la RMN del cervello mostra atrofia cerebrale e cerebellare."},"nl":{"name":"Congenitale contracturen van ledematen en gelaat - hypotonie - ontwikkelingsachterstand-syndroom","synonyms":["CLIFAHDD syndroom"],"definition":"Een zeldzaam meervoudige congenitale anomalieën/dysmorfie-syndroom met intellectuele achterstand, gekarakteriseerd door ernstige congenitale contracturen van ledematen en aangezicht, hypotonie, neonatale ademnood, en algehele ontwikkelingsachterstand. Dysmorfe gelaatskenmerken zijn onder meer schuin naar beneden hellende ooglidspleten, brede neusbrug, grote neusgaten, lang filtrum, en diepe nasolabiale plooien. Misvorming van ledemaat (camptodactylie, klompvoet), korte nek, scoliose, alsook insulten werden ook reeds gerapporteerd. In sommige gevallen kan MRI van hersenen cerebrale en cerebellaire atrofie tonen."},"pt":{"name":"Síndrome de contraturas congénitas dos membros e da face-hipotonia-perturbação do desenvolvimento","synonyms":["Síndrome CLIFAHDD"]},"pl":{"name":"Zespół wrodzonych przykurczy kończyn i twarzy, hipotonii i opóźnionego rozwoju","synonyms":["Zespół CLIFAHDD"]},"cs":{"name":"Syndrom zahrnující vrozené kontraktury končetin a obličeje, hypotonii a opožděný vývoj","synonyms":["CLIFAHDD syndrome"]},"uk":{"name":"Синдром вроджених контрактур кінцівок-контрактур обличчя-гіпотонії-затримки розвитку","synonyms":["Синдром CLIFAHDD"],"definition":"A rare multiple congenital anomalies/dysmorphic syndrome with intellectual disability characterized by severe congenital contractures of the limbs and face, hypotonia, neonatal respiratory distress, and global developmental delay. Dysmorphic facial features include downslanting palpebral fissures, broad nasal bridge, large nares, long philtrum, and deep nasolabial folds, among others. Limb deformities (camptodactyly, clubfoot), short neck, scoliosis, as well as seizures have also been reported. Brain MRI may show cerebral and cerebellar atrophy in some cases."},"zh":{"name":"先天性四肢-面部挛缩-肌张力低下-发育迟缓综合征","synonyms":["CLIFAHDD syndrome"],"definition":"一种罕见的多发性先天性异常/畸形综合征，伴有智力障碍，其特点是四肢和面部严重先天性挛缩、肌张力低下、新生儿呼吸困难和全面发育迟缓。面部畸形特征包括下睑裂、鼻梁宽大、鼻孔大、长人中、鼻唇沟深等。四肢畸形（先天性指屈曲、畸形足）、短颈、脊柱侧弯以及癫痫发作等也有报道。脑核磁共振成像在某些情况下可能显示大脑和小脑萎缩。"},"tr":{"name":"Doğumsal ekstremiteler-yüz kontraktürleri-hipotoni-gelişme geriliği sendromu","synonyms":["CLIFAHDD sendromu"]}},"xrefs":[{"source":"OMIM","code":"616266","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0014556","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4225398","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":97120,"name":"Distal arthrogryposis","classifications":[147,156]},{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":98738,"name":"Neurological muscular channelopathy due to a genetic sodium channel defect","classifications":[156,181]}],"children":[],"genes":[{"symbol":"NALCN","name":"sodium leak channel, non-selective","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"31410997[PMID]","hgnc":"19082","ensembl":"ENSG00000102452","omim":"611549","loci":["13q32.3-q33.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":14.0,"area":"Worldwide","status":"Validated","source":"25683120[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_25683120[PMID]_28133733[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2022-12-14","source":"35911839[PMID]","terms":[{"hpo":"HP:0002804","label":"Arthrogryposis multiplex congenita","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012385","label":"Camptodactyly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012758","label":"Neurodevelopmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002793","label":"Abnormal pattern of respiration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001181","label":"Adducted thumb","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011824","label":"Chin with H-shaped crease","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009931","label":"Enlarged naris","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001371","label":"Flexion contracture","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100790","label":"Hernia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000205","label":"Pursed lips","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002000","label":"Short columella","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001762","label":"Talipes equinovarus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001193","label":"Ulnar deviation of the hand or of fingers of the hand","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000248","label":"Brachycephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000337","label":"Broad forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001848","label":"Calcaneovalgus deformity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002019","label":"Constipation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002307","label":"Drooling","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000565","label":"Esotropia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000160","label":"Narrow mouth","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:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000319","label":"Smooth philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001166","label":"Arachnodactyly","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000256","label":"Macrocephaly","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000400","label":"Macrotia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000417","label":"Slender nose","frequency":"Very rare (<4-1%)","criteria":null}]}}