{"orpha":488632,"name":"TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare multiple congenital anomalies/dysmorphic syndrome characterized by profound intellectual disability with absent speech, severe infantile hypotonia with decreased or absent reflexes, markedly slow motor development (with no progress beyond the ability to sit independently), early-onset epilepsy, strabismus and post-natal onset of progressive brain atrophy (including loss of brain volume, ex vacuo ventriculomegaly, dysgenesis of corpus callosum, white matter abnormalities ranging from non-specific changes to leukodystrophy). Swallowing difficulties, respiratory insufficiency, osteoporosis and variable craniofacial dysmorphisms (including plagio/brachycephaly, bitemporal narrowing, high-arched eyebrows high nasal bridge, anteverted nares, high palate, tented upper lip) may constitute additional clinical features.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-488632/","orphanet_url":"https://www.orpha.net/en/disease/detail/488632","names":{"fr":{"name":"Syndrome d'encéphalopathie-hypotonie sévère-dysmorphie craniofaciale associé à TBCK","definition":"Déficience intellectuelle syndromique rare d'origine génétique caractérisée par une déficience intellectuelle généralement profonde et une absence de langage, une hypotonie infantile sévère avec diminution ou absence de réflexes, un développement moteur très lent (n'allant pas au-delà de la capacité à s'asseoir seul), une épilepsie précoce, un strabisme et l'apparition post-natale d'une atrophie cérébrale progressive (y compris une perte de la masse cérébrale, une ventriculomégalie ex vacuo, une dysgénésie du corps calleux, des anomalies de la substance blanche allant de changements non spécifiques à une leucodystrophie). Difficultés de déglutition, insuffisance respiratoire, ostéoporose et dysmorphie craniofaciale variable (à type de plagiobrachycéphalie, de rétrécissement bitemporal, de sourcils très arqués, de pont nasal haut, de narines antéversées, de palais ogival, de lèvre supérieure en forme de tente) peuvent constituer des caractéristiques cliniques supplémentaires."},"de":{"name":"TBCK-assoziierte Enzephalopathie-schwere Hypotonie-kraniofaziale Dysmorphie-Syndrom","synonyms":["TBCK-Syndrom"],"definition":"Ein seltenes Syndrom mit multiplen kongenitalen Anomalien/Dysmorphien, das durch eine tiefgreifende Intelligenzminderung mit fehlender Sprache, eine schwere infantile Hypotonie mit verminderten oder fehlenden Reflexen und eine deutlich verlangsamte motorische Entwicklung (die über die Fähigkeit, selbständig zu sitzen, nicht hinausgeht) gekennzeichnet ist. Weitere Merkmale sind früh einsetzende Epilepsie, Strabismus und postnatal einsetzende progressive Hirnatrophie (einschließlich Verlust des Hirnvolumens, Ex-vacuo-Ventrikulomegalie, Dysgenesie des Corpus callosum, Anomalien der weißen Substanz, die von unspezifischen Veränderungen bis hin zur Leukodystrophie reichen). Zudem können Schluckstörungen, respiratorische Insuffizienz, Osteoporose und variable kraniofaziale Dysmorphismen (einschließlich Plagio-/Brachyzephalie, bitemporale Verschmälerung, hochgewölbte Augenbrauen, hoher Nasenrücken, antevertierte Nasenlöcher, hoher Gaumen und gespaltene Oberlippe) beobachtet werden."},"es":{"name":"Síndrome de encefalopatía-hipotonía grave-dismorfia craneofacial asociado a TBCK","definition":"Es un síndrome dismórfico/ de múltiples amnomalías congénitas poco frecuente, caracterizado por discapacidad intelectual profunda con ausencia del habla, hipotonía infantil grave con reflejos disminuidos o ausentes, desarrollo motor marcadamente lento (sin progreso más allá de la capacidad de sentarse independientemente), epilepsia de inicio precoz, estrabismo y atrofia cerebral progresiva de inicio postnatal (que incluye pérdida de volumen cerebral, ventriculomegalia ex vacuo, disgenesia del cuerpo calloso, anomalías de la sustancia blanca que van desde cambios inespecíficos hasta leucodistrofia). Otras características clínicas adicionales descritas son: trastornos de la deglución, insuficiencia respiratoria, osteoporosis y dismorfia craneofacial variable (incluyendo plagio / braquicefalia, estrechamiento bitemporal, cejas altas y arqueadas, puente nasal alto, narinas antevertidas, paladar ojival y labio superior en forma de carpa)."},"it":{"name":"Disabilità intellettiva correlata a TBCK","definition":"La disabilità intellettiva correlata a TBCK è una disabilità intellettiva sindromica rara, di origine genetica, caratterizzata da disabilità intellettiva di solito di grado molto elevato, associata ad assenza del linguaggio, ipotonia infantile grave con riduzione o assenza dei riflessi, notevole ritardo dello sviluppo motorio (non si osservano progressi al di fuori della capacità del paziente di stare seduto in maniera indipendente), epilessia ad insorgenza precoce, strabismo ed atrofia cerebrale progressiva ad esordio neonatale (riduzione del volume cerebrale, ventricolomegalia ex vacuo, disgenesia del corpo calloso, anomalie aspecifiche della sostanza bianca fino alla leucodistrofia). Altri segni clinici comprendono le difficoltà di deglutizione, l'insufficienza respiratoria, l'osteoporosi e i dismorfismi craniofacciali variabili (plagio/brachicefalia, restringimento bitemporale, sopracciglia arcuate, radice del naso prominente, narici anteverse, palato ogivale, labbro superiore ''a tenda'')."},"nl":{"name":"TBCK-gerelateerde encefalopathie - ernstige hypotonie - craniofaciale dysmorfie-syndroom","definition":"Een zeldzaam syndroom met multipele congenitale anomalieën/dysmorfie, gekenmerkt door zeer ernstige intellectuele achterstand met afwezige spraak, ernstige infantiele hypotonie met verminderde of afwezige reflexen, opmerkelijk vertraagde motorische ontwikkeling (met geen progressie voorbij het vermogen om zelfstandig te zitten), vroeg optredende epilepsie, strabisme, en postnatale aanvang van progressieve atrofie van hersenen (inclusief verlies van hersenvolume, ex vacuo ventriculomegalie, dysgenesie van corpus callosum, en afwijkingen van witte stof gaande van aspecifieke veranderingen tot leukodystrofie). Mogelijke bijkomende klinische kenmerken zijn moeilijkheden met slikken, respiratoire insufficiëntie, osteoporose en variabele craniofaciale dysmorfie (waaronder plagio-/brachycefalie, bitemporale vernauwing, hoog gebogen wenkbrauwen, hoge neusbrug, anteversie van de neusgaten, hoog gehemelte, tentvormige bovenlip)."},"pt":{"name":"Síndrome de encefalopatia-hipotonia grave-dismorfia craniofacial TBCK-relacionada"},"pl":{"name":"Zespół niepełnosprawności intelektualnej związany z TBCK","definition":"Rzadki zespół mnogich wad wrodzonych / zespół dysmorficzny charakteryzujący się głęboką niepełnosprawnością intelektualną z brakiem rozwoju mowy, ciężką hipotonią niemowlęcą z osłabieniem lub brakiem odruchami, wyraźnie spowolnionym rozwojem ruchowym (bez postępu, poza zdolnością do samodzielnego siedzenia), padaczką o wczesnym początku, zezem i postępującym poporodowym zanikiem mózgu (w tym utratą objętości mózgu, powiększeniem komór mózgu ex vacuo, dysgenezją ciała modzelowatego, nieprawidłowościami istoty białej od niespecyficznych zmian do leukodystrofii). Dodatkowe objawy / cechy kliniczne to trudności z połykaniem, niewydolność oddechowa, osteoporoza i zmienna dysmorfia twarzoczaszki (w tym plagio/brachycefalia, zwężenie dwuskroniowe, wysokie łukowate brwi, wysoki grzbiet nosa, przodopochylone nozdrza, wysokie podniebienie, namiotowata górna warga)."},"cs":{"name":"Syndrom TBCK-vázané mentální retardace"},"uk":{"name":"Синдром інтелектуальної недостатності, повязаний з TBCK","definition":"TBCK-related intellectual disability syndrome is a rare, genetic, syndromic intellectual disability characterized by usually profound intellectual disability with absent speech, severe infantile hypotonia with decreased or absent reflexes, markedly slow motor development (with no progress beyond the ability to sit independently), early-onset epilepsy, strabismus and post-natal onset of progressive brain atrophy (incl. loss of brain volume, ex vacuo ventriculomegaly, dysgenesis of corpus callosum, white matter abnormalities ranging from non-specific changes to leukodystrophy). Swallowing difficulties, respiratory insufficiency, osteoporosis and variable craniofacial dysmorphisms (incl. plagio/brachicephaly, bitemporal narrowing, high-arched eyebrows, high nasal bridge, anteverted nares, high palate, tented upper lip) may constitute additional clinical features."},"zh":{"name":"TBCK相关智力障碍综合征","definition":"TBCK基因相关智力障碍综合征是一种罕见的遗传性综合征性智力障碍，其特征是通常有深度智力障碍，伴有言语缺失，严重的婴儿肌张力低下，反射减弱或消失，运动发育明显缓慢(除了独立坐姿的能力外没有任何进步)，早发性癫痫，斜视和出生后出现的进行性脑萎缩(包括脑容量丧失，补空性脑室扩大，胼胝体发育不良，白质从非特异性变化到白质营养不良性异常)。吞咽困难、呼吸功能不全、骨质疏松和不同的颅面畸形（包括斜头/短头畸形、双颞部狭窄、高弓眉、高鼻梁、鼻孔前倾、高腭、帐篷状上唇）可能构成额外的临床特征。"},"tr":{"name":"TBCK -ilişkili zihinsel yetersizlik sendromu"}},"xrefs":[{"source":"OMIM","code":"616900","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.0","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD90.Y","qualifier":"NTBT","icd_relation":"attributed","validated":false},{"source":"MONDO","code":"0014823","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5567480","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]}],"children":[],"genes":[{"symbol":"TBCK","name":"TBC1 domain containing kinase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"27040691[PMID]_27040692[PMID]_27275012[PMID]_27748029[PMID]_18541960[PMID]","hgnc":"28261","ensembl":"ENSG00000145348","omim":"616899","loci":["4q24"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":25.0,"area":"Worldwide","status":"Validated","source":"27748029[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_27748029[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-01-13","source":"29283439[PMID]_27748029[PMID]_25558065[PMID]_27040691[PMID]","terms":[{"hpo":"HP:0003444","label":"EMG: chronic denervation signs","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001319","label":"Neonatal hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003323","label":"Progressive muscle weakness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0006829","label":"Severe muscular hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003119","label":"Abnormal circulating lipid concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002518","label":"Abnormal periventricular white matter morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001284","label":"Areflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000280","label":"Coarse facial features","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002283","label":"Global brain atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031165","label":"Multifocal seizures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001315","label":"Reduced tendon reflexes","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002093","label":"Respiratory insufficiency","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011344","label":"Severe global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003202","label":"Skeletal muscle atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000337","label":"Broad forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000414","label":"Bulbous nose","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100543","label":"Cognitive impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002750","label":"Delayed skeletal maturation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011198","label":"EEG with generalized epileptiform discharges","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100288","label":"EMG: myokymic discharges","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002705","label":"High, narrow palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001007","label":"Hirsutism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002045","label":"Hypothermia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000821","label":"Hypothyroidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009826","label":"Limb undergrowth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000256","label":"Macrocephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000158","label":"Macroglossia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000939","label":"Osteoporosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000767","label":"Pectus excavatum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000340","label":"Sloping forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010804","label":"Tented upper lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000574","label":"Thick eyebrow","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001629","label":"Ventricular septal defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000878","label":"11 pairs of ribs","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0004691","label":"2-3 toe syndactyly","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0012547","label":"Abnormal involuntary eye movements","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002099","label":"Asthma","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000717","label":"Autism","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0007302","label":"Bipolar affective disorder","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001500","label":"Broad finger","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001837","label":"Broad toe","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0011734","label":"Central adrenal insufficiency","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0030084","label":"Clinodactyly","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0007957","label":"Corneal opacity","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000824","label":"Decreased response to growth hormone stimulation test","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000490","label":"Deeply set eye","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001540","label":"Diastasis recti","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000964","label":"Eczematoid dermatitis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000836","label":"Hyperthyroidism","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000303","label":"Mandibular prognathia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000011","label":"Neurogenic bladder","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001562","label":"Oligohydramnios","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0005487","label":"Prominent metopic ridge","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001642","label":"Pulmonic stenosis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000664","label":"Synophrys","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000582","label":"Upslanted palpebral fissure","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Very rare (<4-1%)","criteria":null}]}}