{"orpha":536545,"name":"Kyphoscoliotic Ehlers-Danlos syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Ehlers-Danlos syndrome type 6","Kyphoscoliotic EDS","kEDS","EDS VI"],"definition":"A rare systemic disease for which two subtypes exist, either related to the gene <i>PLOD1</i> or <i>FKBP22</i>, and for which the clinically overlapping characteristics include congenital muscle hypotonia, congenital or early-onset kyphoscoliosis (progressive or non-progressive), and generalized joint hypermobility with dislocations/subluxations (in particular of the shoulders, hips, and knees). Additional features which may occur in both subtypes are skin hyperextensibility, easy bruising of the skin, rupture/aneurysm of a medium-sized artery, osteopenia/osteoporosis, blue sclerae, umbilical or inguinal hernia, chest deformity, marfanoid habitus, talipes equinovarus, and refractive errors. Gene-specific features, with variable presentation, are additionally observed in each subtype.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-536545/","orphanet_url":"https://www.orpha.net/en/disease/detail/536545","names":{"fr":{"name":"Syndrome d'Ehlers-Danlos type cyphoscoliotique","synonyms":["EDS type cyphoscoliotique","SED VI","SED type cyphoscoliotique","SEDk","Syndrome d'Ehlers-Danlos type 6","Syndrome d'Ehlers-Danlos type oculo-scoliotique"],"definition":"Maladie systémique rare dont il existe deux sous-types, liés soit au gène <i>PLOD1</i>, soit au gène <i>FKBP22</i>, et dont les signes cliniques communs sont : l'hypotonie musculaire congénitale, la cyphoscoliose congénitale ou précoce (progressive ou non) et l'hypermobilité articulaire généralisée avec dislocations/subluxations (en particulier des épaules, des hanches et des genoux). Parmi d'autres caractéristiques communes figurent l'hyperextensibilité de la peau, la tendance aux ecchymoses, la rupture/l'anévrisme d'une artère de taille moyenne, l'ostéopénie/l'ostéoporose, les sclérotiques bleutées, la hernie ombilicale ou inguinale, la déformation de la poitrine, un habitus marfanoïde, le talipes equinovarus et les erreurs de réfraction. Par ailleurs, dans chaque sous-type, on observe des caractéristiques variables, spécifiques aux gènes."},"de":{"name":"Ehlers-Danlos-Syndrom, kyphoskoliotischer Typ","synonyms":["EDS VI","EDS, kyphoskoliotisches","Ehlers-Danlos-Syndrom Typ 6","kEDS"],"definition":"Eine seltene Systemerkrankung, für die zwei Subtypen existieren, die entweder mit dem <i>PLOD1</i>- oder dem <i>FKBP22</i>-Gen assoziiert sind und deren gemeinsame klinische Merkmale kongenitale Muskelhypotonie, kongenitale oder frühkindliche (progressive oder nicht progressive) Kyphoskoliose und generalisierte Gelenkhypermobilität mit Dislokationen/Subluxationen (insbesondere der Schultern, Hüften und Knie) sind. Weitere gemeinsame Manifestationen sind Dehnbarkeit der Haut, leichte Hämatome der Haut, Ruptur/Aneurysma einer mittelgroßen Arterie, Osteopenie/Osteoporose, blaue Skleren, Nabel- oder Leistenbruch, Brustdeformität, marfanoider Habitus, Klumpfüße und Refraktionsfehler. Beide Subtypen weisen zudem zusätzliche spezifische Merkmale mit unterschiedlicher Ausprägung auf."},"es":{"name":"Síndrome de Ehlers-Danlos cifoescoliótico","synonyms":["SED VI","SED cifoescoliótico","SED oculoescoliótico","SED óculo-escoliótico","Síndrome de Ehlers-Danlos tipo 6"],"definition":"Es una enfermedad sistémica poco frecuente para la que existen dos subtipos asociados a los genes <i>PLOD1</i> o <i>FKBP22</i>. Los hallazgos compartidos incluyen hipotonía muscular congénita, cifoscoliosis congénita o de inicio temprano (progresiva o no progresiva) e hipermovilidad articular generalizada con luxaciones/subluxaciones (en particular de los hombros, caderas y rodillas). Otros hallazgos adicionales que pueden estar presentes en ambos subtipos son hiperextensibilidad cutánea, propensión a hematomas cutáneos, ruptura/ aneurisma de las arterias medias, osteopenia/osteoporosis, escleróticas azules, hernia umbilical o inguinal, deformidades torácicas, hábito marfanoide, pie zambo y errores de refracción. Adicionalmente, en cada subtipo se observan otros hallazgos específicos asociados a cada gen en particular con una presentación variable."},"it":{"name":"Sindrome di Ehlers-Danlos cifoscoliotica","definition":"Si tratta di una malattia sistemica rara, di cui esistono due sottotipi, uno correlato al gene <i>PLOD1</i> e l'altro al gene <i>FKBP22</i> . I segni clinici sono sovrapponibili e comprendono l'ipotonia muscolare congenita, la cifoscoliosi congenita o ad esordio precoce (progressiva o non progressiva) e l'ipermobilità articolare generalizzata associata a dislocazioni/sublussazioni (in particolare della spalla, dell'anca e del ginocchio). Altri segni clinici caratteristici di entrambi i sottotipi sono l'iperestensibilità della cute, la tendenza alle ecchimosi, la rottura/gli aneurismi delle arterie di media grandezza, l'osteopenia/osteoporosi, le sclere blu, l'ernia ombelicale o inguinale, le deformità del torace, l'habitus marfanoide, i piedi equino-vari e gli errori refrattivi. Ogni sottotipo presenta inoltre segni clinici specifici correlati al gene interessato."},"nl":{"name":"Kyfoscoliotisch syndroom van Ehlers-Danlos","synonyms":["EDS VI","Kyfoscoliotisch EDS","Syndroom van Ehlers-Danlos type 6","kEDS"],"definition":"Een zeldzame systemische waarvan twee subtypes bestaan, gerelateerd aan ofwel het gen <i>PLOD1</i> ofwel het gen <i>FKBP22</i>, met klinisch overlappende kenmerken, waaronder congenitale spierhypotonie, congenitale of vroeg aanvangende kyfoscoliose (progressief of niet-progressief), en gegeneraliseerde gewrichtshypermobiliteit met dislocaties/subluxaties (vooral van schouder, heup, en knie). Bijkomende kenmerken die bij beide subtypes kunnen voorkomen, zijn hyperelastische huid, gevoeligheid voor kneuzing van huid, ruptuur/aneurysma van een middelgrote arterie, osteopenie/osteoporose, blauwe sclerae, navel- of liesbreuk, misvorming van borstkas, marfanoïde habitus, talipes equinovarus, en refractiefouten. Genspecifieke kenmerken, met variabele presentatie, worden bijkomend geobserveerd bij elk subtype."},"pt":{"name":"Síndrome Ehlers-Danlos cifoescoliótico"},"pl":{"name":"Zespół Ehlersa i Danlosa z kifoskoliozą","synonyms":["Ehlers-Danlos syndrome type 6"]},"cs":{"name":"Ehlersův-Danlosův syndrom, kyfoskoliotický typ","synonyms":["kEDS","EDS VI","EDS, kyfoskoliotický typ","EDS, okuloskoliotický typ","Ehlersův-Danlosův syndrom, typ 6","Ehlers-Danlosův syndrom, kyfoskoliotický typ","Ehlers-Danlosův syndrom, typ 6"]},"uk":{"name":"Кіфосколіотичний синдром Елерса-Данлоса","synonyms":["EDS VI","Синдром Елерса-Данлоса, тип 6","kEDS","Кіфосколіотичний EDS"],"definition":"A rare systemic disease for which two subtypes exist, either related to the gene <i>PLOD1</i> or <i>FKBP22</i>, and for which the clinically overlapping characteristics include congenital muscle hypotonia, congenital or early-onset kyphoscoliosis (progressive or non-progressive), and generalized joint hypermobility with dislocations/subluxations (in particular of the shoulders, hips, and knees). Additional features which may occur in both subtypes are skin hyperextensibility, easy bruising of the skin, rupture/aneurysm of a medium-sized artery, osteopenia/osteoporosis, blue sclerae, umbilical or inguinal hernia, chest deformity, marfanoid habitus, talipes equinovarus, and refractive errors. Gene-specific features, with variable presentation, are additionally observed in each subtype."},"zh":{"name":"脊柱后凸畸形埃勒斯-当洛斯综合征","synonyms":["Kyphoscoliotic EDS"],"definition":"一种罕见的全身性疾病，存在两个亚型，要么与PLOD1基因有关，要么与FKBP22基因有关，其临床重叠的特征包括先天性肌张力低下、先天性或早发性脊柱后凸侧弯（进行性或非进行性）和全身关节活动过度，伴有脱位/不全脱位（尤其是肩、髋和膝）。两种亚型都可能出现的其他特征有：皮肤过度伸展、皮肤容易瘀伤、中等大小动脉破裂/动脉瘤、骨质减少/骨质疏松、蓝巩膜、脐疝或腹股沟疝、胸部畸形、马方综合征体型、马蹄内翻足和屈光不正。在每个亚型中还可观察到基因特异性的特征，表现各异。"},"tr":{"name":"Kifoskolyotik Ehlers-Danlos sendromu","synonyms":["kEDS","EDS VI","Kifoskolyotik EDS","Ehlers-Danlos sendromu tip 6"]}},"xrefs":[{"source":"ICD-10","code":"Q79.6","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD28.1Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1397391838"},{"source":"MONDO","code":"0034024","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C536198","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4551497","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"2083","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98023,"name":"Rare systemic or rheumatologic disease"},"parents":[{"orpha":98249,"name":"Ehlers-Danlos syndrome","classifications":[147,156,187,196]}],"children":[{"orpha":300179,"name":"Kyphoscoliotic Ehlers-Danlos syndrome due to FKBP22 deficiency","type":"Clinical subtype"},{"orpha":1900,"name":"Kyphoscoliotic Ehlers-Danlos syndrome due to lysyl hydroxylase 1 deficiency","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"FKBP14","name":"FKBP prolyl isomerase 14","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22265013[PMID]","hgnc":"18625","ensembl":"ENSG00000106080","omim":"614505","loci":["7p14.3"],"via":{"orpha":300179,"name":"Kyphoscoliotic Ehlers-Danlos syndrome due to FKBP22 deficiency"}},{"symbol":"PLOD1","name":"procollagen-lysine,2-oxoglutarate 5-dioxygenase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"15979919[PMID]_20301635[PMID]","hgnc":"9081","ensembl":"ENSG00000083444","omim":"153454","loci":["1p36.22"],"via":{"orpha":1900,"name":"Kyphoscoliotic Ehlers-Danlos syndrome due to lysyl hydroxylase 1 deficiency"}}],"inheritance":[],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_28306225[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-11-14","source":"20301635[PMID]_31132235[PMID]_28306225[PMID]","terms":[{"hpo":"HP:0002761","label":"Generalized joint hypermobility","frequency":"Very frequent (99-80%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002751","label":"Kyphoscoliosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000766","label":"Abnormal sternum morphology","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000987","label":"Atypical scarring of skin","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000978","label":"Bruising susceptibility","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0008453","label":"Congenital kyphoscoliosis","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0002194","label":"Delayed gross motor development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001030","label":"Fragile skin","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000974","label":"Hyperextensible skin","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000540","label":"Hypermetropia","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0001373","label":"Joint dislocation","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001319","label":"Neonatal hypotonia","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0001027","label":"Soft, doughy skin","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000664","label":"Synophrys","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001760","label":"Abnormal foot morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001155","label":"Abnormality of the hand","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007023","label":"Antenatal intracerebral hemorrhage","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001166","label":"Arachnodactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025019","label":"Arterial rupture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000592","label":"Blue sclerae","frequency":"Occasional (29-5%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0001342","label":"Cerebral hemorrhage","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001374","label":"Congenital hip dislocation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001558","label":"Decreased fetal movement","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001519","label":"Disproportionate tall stature","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007502","label":"Follicular hyperkeratosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002827","label":"Hip dislocation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000023","label":"Inguinal hernia","frequency":"Occasional (29-5%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000482","label":"Microcornea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Occasional (29-5%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000938","label":"Osteopenia","frequency":"Occasional (29-5%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000767","label":"Pectus excavatum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001763","label":"Pes planus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001058","label":"Poor wound healing","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003834","label":"Shoulder dislocation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003202","label":"Skeletal muscle atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001328","label":"Specific learning disability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010727","label":"Spontaneous rupture of the globe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001762","label":"Talipes equinovarus","frequency":"Occasional (29-5%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000963","label":"Thin skin","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001537","label":"Umbilical hernia","frequency":"Occasional (29-5%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000422","label":"Abnormality of the nasal bridge","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0004942","label":"Aortic aneurysm","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0003467","label":"Atlantoaxial instability","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001647","label":"Bicuspid aortic valve","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000015","label":"Bladder diverticulum","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000405","label":"Conductive hearing impairment","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001651","label":"Dextrocardia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0003994","label":"Dislocated wrist","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000601","label":"Hypotelorism","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0004976","label":"Knee dislocation","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000276","label":"Long face","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0003198","label":"Myopathy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000939","label":"Osteoporosis","frequency":"Very rare (<4-1%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000768","label":"Pectus carinatum","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0100309","label":"Subdural hemorrhage","frequency":"Very rare (<4-1%)","criteria":null}]}}