{"orpha":457359,"name":"Megalencephaly-severe kyphoscoliosis-overgrowth syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by overgrowth and macrocephaly with megalencephaly apparent at birth, global developmental delay, intellectual disability, and dysmorphic facial features (including frontal bossing, long face, sparse eyebrows, hypertelorism, downslanting palpebral fissures, and prognathism). Patients may exhibit tall stature with dolichostenomelia, arachnodactyly, kyphoscoliosis, and joint laxity, as well as neurologic manifestations, such as hypotonia, gait ataxia, or seizures. Brain imaging may show increased white matter volume, thick corpus callosum, or small cerebellum.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-457359/","orphanet_url":"https://www.orpha.net/en/disease/detail/457359","names":{"fr":{"name":"Syndrome de croissance excessive-mégalencéphalie-cyphoscoliose sévère","definition":"Anomalies congénitales multiples/syndrome dysmorphique rare d'origine génétique caractérisé par une croissance excessive, une macrocéphalie avec une mégalencéphalie apparente à la naissance, un retard de développement global, une déficience intellectuelle et une dysmorphie faciale (à savoir une bosse frontale, un visage allongé, des sourcils peu fournis, un hypertélorisme, des fentes palpébrales inclinées vers le bas et un prognathisme). Les patients sont de grande taille, présentant une dolichosténomélie, une arachnodactylie, une cyphoscoliose et une laxité articulaire, ainsi que des signes cliniques neurologiques à savoir une hypotonie, une ataxie de la marche ou des crises convulsives. L'imagerie cérébrale peut mettre en évidence une augmentation du volume de la substance blanche, un épaississement du corps calleux ou une atrophie du cervelet."},"de":{"name":"Megalenzephalie-schwere Kyphoskoliose-Großwuchs-Syndrom","definition":"Ein seltenes genetisch bedingtes Dysmorphie-Syndrom, das durch Überwuchs und Makrozephalie mit bei der Geburt sichtbarer Megalenzephalie, globale Entwicklungsverzögerung, Intelligenzminderung und dysmorphe Gesichtsmerkmale (einschließlich Balkonstirn, langes Gesicht, schräg abwärts verlaufende Lidspalten und Prognathie) gekennzeichnet ist. Die Patienten können eine hohe Statur mit Dolichostenomelie, Arachnodaktylie, Kyphoskoliose und Gelenklaxität sowie neurologische Manifestationen wie Hypotonie, Gangataxie oder Krampfanfälle aufweisen. Die zerebrale Bildgebung kann ein erhöhtes Volumen der weißen Substanz, ein dickes Corpus callosum oder ein kleines Cerebellum zeigen."},"es":{"name":"Síndrome de megalencefalia-cifoscoliosis grave-sobrecrecimiento","definition":"Es un síndrome dismórfico/ de múltiples anomalías congénitas de base genética y poco frecuente caracterizado por sobrecrecimiento y macrocefalia con megalencefalia aparente al nacimiento, retraso global del desarrollo psicomotor, discapacidad intelectual y rasgos faciales dismórficos (incluyendo frente prominente, cara alargada, cejas escasas, hipertelorismo, fisuras palpebrales descendentes y prognatismo). Los pacientes pueden presentar talla alta con dolicostenomelia, aracnodactilia, cifoescoliosis y laxitud articular, así como manifestaciones neurológicas, como hipotonía, ataxia de la marcha o crisis convulsivas. Las neuroimágenes pueden mostrar un aumento del volumen de sustancia blanca, engrosamiento del cuerpo calloso o hipoplasia cerebelosa."},"it":{"name":"Sindrome megalencefalia - cifoscoliosi grave - iperaccrescimento","definition":"Si tratta di una malattia genetica rara da anomalie/dismorfismi congeniti multipli, caratterizzata da iperaccrescimento e macrocefalia con megalencefalia congenita, ritardo dello sviluppo globale, disabilità intellettiva e dismorfismi facciali (fronte bombata, viso allungato, sopracciglia rade, ipertelorismo, rime palpebrali oblique verso il basso e prognatismo). I pazienti possono presentare alta statura con dolicostenomelia, aracnodattilia, cifoscoliosi, lassità articolare e sintomi neurologici (ipotonia, atassia dell'andatura o crisi epilettiche). Le neuroimmagini mostrano un aumento del volume della sostanza bianca, un ispessimento del corpo calloso e ipoplasia del cervelletto."},"nl":{"name":"Megalencefalie - ernstige kyfoscoliose - overgroei-syndroom","definition":"Een zeldzaam, genetisch syndroom met multipele congenitale anomalieën/dysmorfie, gekarakteriseerd door overgroei en macrocefalie met megalencefalie merkbaar bij de geboorte, algehele ontwikkelingsachterstand, intellectuele achterstand, en dysmorfe gelaatskenmerken (waaronder boller voorhoofd, lang aangezicht, schaarse wenkbrauwen, hypertelorisme, schuin naar beneden hellende ooglidspleten, en prognathie). Patiënten vertonen mogelijk lange gestalte met dolichostenomelie, arachnodactylie, kyfoscoliose, en gewrichtslaxiteit, alsook neurologische manifestaties, waaronder hypotonie, gangataxie, of insulten. Beeldvorming van hersenen toont mogelijk verhoogd volume van witte stof, dik corpus callosum, of klein cerebellum."},"pt":{"name":"Síndrome de megalencefalia-cifoescoliose grave-sobrecrescimento"},"pl":{"name":"Zespół mózgu olbrzymiego, ciężkiej kifoskoliozy i przerostu"},"cs":{"name":"Syndrom zahrnující megalencefalii, těžkou kyfoskoliózu a nadměrný růst"},"uk":{"name":"Синдром мегаленцефалії-тяжкого кіфосколіозу-надмірного росту","definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by overgrowth and macrocephaly with megalencephaly apparent at birth, global developmental delay, intellectual disability, and dysmorphic facial features (including frontal bossing, long face, sparse eyebrows, hypertelorism, downslanting palpebral fissures, and prognathism). Patients may exhibit tall stature with dolichostenomelia, arachnodactyly, kyphoscoliosis, and joint laxity, as well as neurologic manifestations, such as hypotonia, gait ataxia, or seizures. Brain imaging may show increased white matter volume, thick corpus callosum, or small cerebellum."},"zh":{"name":"巨颅畸形-严重脊柱后凸-过度生长综合征"},"tr":{"name":"Megalensefali-ağır kifoskolyoz-aşırı büyüme sendromu"}},"xrefs":[{"source":"OMIM","code":"617011","qualifier":"NTBT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.3","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD2C","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0018710","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5681123","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"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":93460,"name":"Overgrowth syndrome","classifications":[147,156]}],"children":[],"genes":[{"symbol":"HERC1","name":"HECT and RLD domain containing E3 ubiquitin protein ligase family member 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"26138117[PMID]_27108999[PMID]","hgnc":"4867","ensembl":"ENSG00000103657","omim":"605109","loci":["15q22.31"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":2.0,"area":"Worldwide","status":"Validated","source":"26138117[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_26138117[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-12-13","source":"26138117[PMID]_26153217[PMID]_27108999[PMID]","terms":[{"hpo":"HP:0001166","label":"Arachnodactyly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011229","label":"Broad eyebrow","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000276","label":"Long face","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001548","label":"Overgrowth","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011220","label":"Prominent forehead","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0045075","label":"Sparse eyebrow","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002069","label":"Bilateral tonic-clonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001519","label":"Disproportionate tall stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002307","label":"Drooling","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002066","label":"Gait ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002751","label":"Kyphoscoliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001520","label":"Large for gestational age","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001833","label":"Long foot","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000256","label":"Macrocephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000400","label":"Macrotia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000303","label":"Mandibular prognathia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001355","label":"Megalencephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000520","label":"Proptosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001533","label":"Slender build","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000582","label":"Upslanted palpebral fissure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001555","label":"Asymmetry of the thorax","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001334","label":"Communicating hydrocephalus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007204","label":"Diffuse white matter abnormalities","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000297","label":"Facial hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011003","label":"High myopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002808","label":"Kyphosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001376","label":"Limitation of joint mobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000472","label":"Long neck","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002938","label":"Lumbar hyperlordosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000272","label":"Malar flattening","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011330","label":"Metopic synostosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000054","label":"Micropenis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001998","label":"Neonatal hypoglycemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001763","label":"Pes planus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000426","label":"Prominent nasal bridge","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012760","label":"Reduced social responsiveness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006863","label":"Severe expressive language delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000586","label":"Shallow orbits","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007074","label":"Thick corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000325","label":"Triangular face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null}]}}