{"orpha":217335,"name":"RIN2 syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["MACS syndrome","Macrocephaly-alopecia-cutis laxa-scoliosis syndrome","RIN2 deficiency","Tall forehead-sparse hair-skin hyperextensibility-scoliosis syndrome"],"definition":"RIN2 syndrome, formerly known as macrocephaly, alopecia, cutis laxa and scoliosis (MACS) syndrome, is a very rare inherited connective tissue disorder characterized by macrocephaly, sparse scalp hair, soft-redundant and hyperextensible skin, joint hypermobility, and scoliosis. Patients have progressive facial coarsening with downslanted palpebral fissures, upper eyelid fullness/infraorbital folds, thick/everted vermillion, gingival overgrowth and abnormal position of the teeth. Rarer manifestations such as abnormal high-pitched voice, bronchiectasis, hypergonadotropic hypergonadism and brachydactyly have also been reported.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-217335/","orphanet_url":"https://www.orpha.net/en/disease/detail/217335","names":{"fr":{"name":"Syndrome RIN2","synonyms":["Déficit en RIN2","Syndrome MACS","Syndrome de macrocéphalie-alopécie-cutis laxa-scoliose"],"definition":"Le syndrome RIN2, anciennement connu sous le nom de macrocéphalie-alopécie-cutis laxa-scoliose (syndrome MACS) est un trouble du tissu conjonctif héréditaire très rare, caractérisé par une macrocéphalie, des cheveux épars, une peau douce, redondante et hyperextensible, une hypermobilité des articulations et une scoliose. Les patients ont une accentuation progressive des traits du visage avec des fentes palpébrales obliquées en bas et en dehors, remplissage des paupières supérieures/plis infraorbitaux, un vermillon épaissi/éversé, une hypertrophie gingivale et une malposition dentaire. Des manifestations plus rares, telles qu'une voix anormalement haut perchée, une bronchectasie, un hypergonadisme hypergonadotropique et une brachydactylie ont également été rapportés."},"de":{"name":"RIN2-Syndrom","synonyms":["Hohe Stirn-Spärliches Haar-Überdehnbarkeit der Haut-Skoliose-Syndrom","MACS-Syndrom","Makrozephalie-Alopezie-Cutis laxa-Skoliose-Syndrom","RIN2-Mangel"]},"es":{"name":"Síndrome RIN2","synonyms":["Deficiencia de RIN2","Síndrome MACS","Síndrome de frente alta-cabello escaso-hiperextensibilidad de la piel-escoliosis","Síndrome de macrocefalia-alopecia-cutis laxa-escoliosis"],"definition":"El síndrome RIN2, anteriormente conocido como síndrome MACS (macrocefalia, alopecia, cutis laxa y escoliosis), es un trastorno hereditario muy raro del tejido conectivo caracterizado por macrocefalia, pelo ralo, piel redundante e hiperextensible, hipermovilidad de las articulaciones y escoliosis. Los pacientes experimentan tosquedad progresiva de los rasgos faciales con inclinación descendente de las fisuras palpebrales, plenitud del párpado superior / pliegues infraorbitales, labios gruesos o evertidos, sobrecrecimiento de las encías y posición anómala de los dientes. También se han registrado manifestaciones más raras, tales como voz aguda anómala, bronquiectasias, hipergonadismo hipergonadotrópico y braquidactilia (véanse estos términos)."},"it":{"name":"Sindrome RIN2","synonyms":["Deficit di RIN2","Sindrome MACS","Sindrome fronte alta-capelli radi-cute iperestensibile-scoliosi","Sindrome macrocefalia-alopecia-cutis laxa-scoliosi"],"definition":"La sindrome RIN2, in precedenza nota come sindrome macrocefalia-alopecia-cutis laxa-scoliosi (MACS), è una malattia ereditaria molto rara del tessuto connettivo, caratterizzata da macrocefalia, capelli radi, cute morbida, in eccesso e iperestensibile, ipermobilità articolare, e scoliosi. I lineamenti facciali dei pazienti diventano con il tempo sempre più grossolani, con rime palpebrali oblique verso il basso, pieghe infraorbitali/pienezza della palpebra superiore, vermiglio spesso rovesciato, iperaccrescimento gengivale e posizione anomala dei denti. Sono stati descritti anche segni più rari, come la voce abnormemente acuta, le bronchiectasie, l'ipergonadismo ipergonadotropo e la brachidattilia (si veda questo termine)."},"nl":{"name":"RIN2-syndroom","synonyms":["Hoog voorhoofd - dun haar - hyperextensibiliteit van de huid - scoliose-syndroom","MACS-syndroom","Macrocefalie - alopecie - cutis laxa - scoliose-syndroom","RIN2-deficiëntie"],"definition":"Een zeer zeldzame erfelijke aandoening van bindweefsel, gekarakteriseerd door macrocefalie, schaars hoofdhaar, zachte, overtollige en hyperuitrekbare huid, gewrichtshypermobiliteit en scoliose. Patiënten hebben progressieve gezichtsverruwing met schuin naar beneden gerichte oogspleten, volle bovenste oogleden/infraorbitale plooien, dik/omgekeerd vermiljoen, overmatige groei van tandvlees en abnormale positie van tanden. Zeldzamere manifestaties zoals abnormaal hoge stem, bronchiëctasie, hypergonadotroop hypergonadisme en brachydactylie werden ook reeds gerapporteerd."},"pt":{"name":"Síndrome de MACS","definition":"A microdeleção 19q13.11 é caracterizada por várias alterações principais, incluindo atraso de crescimento pré e pós-natal, hábito fino, graves dificuldades na alimentação pós-natal, microcefalia, défice cognitivo com distúrbio da fala, hipospádias e displasia ectodérmica caracterizada por aplasia do couro cabeludo, cabelo, sobrancelhas e pestanas finos e esparsos, pele fina e seca e unhas displásicas."},"pl":{"name":"Zespół RIN2","synonyms":["Niedobór RIN2","Zespół MACS","Zespół makrocefalii, łysienia, luźnej skóry i skoliozy"]},"cs":{"name":"RIN2 syndrom","synonyms":["MACS syndrom","Syndrom zahrnující makrocefalii, alopecii, cutis laxa a skoliózu","RIN2 deficit","Syndrom zahrnující vysoké čelo, řídké vlasy, hyperextensibilitu kůže a skoliózu"]},"uk":{"name":"Синдром RIN2","synonyms":["Синдром макроцефалії - алопеції - cutis laxa - сколіозу","Синдром MACS","Дефіцит RIN2","Синдром високого лобу - рідкого волосся - надмірної розтяжност шкіри - сколіозу"],"definition":"RIN2 syndrome, formerly known as macrocephaly, alopecia, cutis laxa and scoliosis (MACS) syndrome, is a very rare inherited connective tissue disorder characterized by macrocephaly, sparse scalp hair, soft-redundant and hyperextensible skin, joint hypermobility, and scoliosis. Patients have progressive facial coarsening with downslanted palpebral fissures, upper eyelid fullness/infraorbital folds, thick/everted vermillion, gingival overgrowth and abnormal position of the teeth. Rarer manifestations such as abnormal high-pitched voice, bronchiectasis, hypergonadotropic hypergonadism and brachydactyly (see this term) have also been reported."},"zh":{"name":"RIN2基因综合征","synonyms":["高额头-头发稀疏-皮肤松弛-脊柱侧凸综合征"],"definition":"RIN2综合征，以前被称为巨头-秃头症-皮肤松弛-脊柱侧凸（MACS）综合征，是一种非常罕见的遗传性结缔组织疾病，其特征是巨头、头发稀疏、过度柔软和过度伸展的皮肤、关节过度活动和脊柱侧凸。患者表现为进行性面容粗糙，睑裂降低，上睑肿胀/眶下皱褶，唇红增厚/外翻，牙龈过度生长和牙齿位置异常。更罕见的表现，如不正常的高音，支气管扩张，高促性腺激素性性腺功能增高和短指畸形（见该词条）也有报道。"},"tr":{"name":"RIN2 sendromu","synonyms":["MACS sendromu","RIN2 eksikliği","Makrosefali-alopesi-kutis laksa-skolyoz sendromu","Uzun alın-seyrek saç-aşırı esnek deri-skolyoz sendromu"]}},"xrefs":[{"source":"OMIM","code":"613075","qualifier":"E","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":"648412341"},{"source":"MONDO","code":"0013115","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C567770","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C2751321","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":209,"name":"Cutis laxa","classifications":[147,156,182,186,187]},{"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]}],"children":[],"genes":[{"symbol":"RIN2","name":"Ras and Rab interactor 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"19631308[PMID]_24449201[PMID]","hgnc":"18750","ensembl":"ENSG00000132669","omim":"610222","loci":["20p11.23"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":10.0,"area":"Worldwide","status":"Validated","source":"27277385[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_27277385[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2017-01-05","source":"24449201[PMID]","terms":[{"hpo":"HP:0000159","label":"Abnormal lip morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000280","label":"Coarse facial features","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000212","label":"Gingival overgrowth","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001007","label":"Hirsutism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000974","label":"Hyperextensible skin","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011232","label":"Infra-orbital fold","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0040079","label":"Irregular dentition","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001763","label":"Pes planus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001582","label":"Redundant skin","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002209","label":"Sparse scalp hair","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012724","label":"Upper eyelid edema","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000766","label":"Abnormal sternum morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001620","label":"Abnormally high-pitched voice","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000978","label":"Bruising susceptibility","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100543","label":"Cognitive impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001537","label":"Umbilical hernia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004942","label":"Aortic aneurysm","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001156","label":"Brachydactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011003","label":"High myopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000815","label":"Hypergonadotropic hypogonadism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002659","label":"Increased susceptibility to fractures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008209","label":"Premature ovarian insufficiency","frequency":"Occasional (29-5%)","criteria":null}]}}