{"orpha":391408,"name":"Primary microcephaly-mild intellectual disability-young-onset diabetes syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare, genetic, syndromic intellectual disability disorder characterized by congenital, persistent microcephaly, low birth weight, short stature, childhood-onset seizures, global development delay, mild intellectual disability, and adolescent or young adult-onset diabetes mellitus. Gait ataxia, skeletal abnormalities, dorsocervical fat pad, and infantile cirrhosis may also be associated. Brain morphology is typically normal, although delayed myelination and hypoplastic brainstem have been reported.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-391408/","orphanet_url":"https://www.orpha.net/en/disease/detail/391408","names":{"fr":{"name":"Syndrome de microcéphalie primaire-déficience intellectuelle modérée-diabète juvénile","definition":"Déficience intellectuelle syndromique rare d'origine génétique caractérisée par une microcéphalie congénitale persistante, un faible poids à la naissance, une petite taille, des convulsions apparaissant pendant l'enfance, un retard de développement global, une déficience intellectuelle légère et un diabète sucré apparaissant à l'adolescence ou chez le jeune adulte. Une ataxie de la démarche, des anomalies squelettiques, un coussinet adipeux dorsocervical et une cirrhose infantile peuvent également être associés. La morphologie du cerveau est généralement normale, bien que des cas de retard de myélinisation et d'hypoplasie du tronc cérébral aient été rapportés."},"de":{"name":"Primäre Mikrozephalie-milde Intelligenzminderung-früh beginnender Diabetes-Syndrom"},"es":{"name":"Síndrome de microcefalia primaria-discapacidad intelectual leve-diabetes de inicio juvenil","definition":"Es un trastorno de discapacidad intelectual sindrómica, genético y poco frecuente, caracterizado por microcefalia congénita persistente, bajo peso al nacer, talla baja, convulsiones de inicio en la infancia, retraso del desarrollo global, discapacidad intelectual leve y diabetes mellitus de inicio en la adolescencia o en el adulto joven. También pueden estar asociadas ataxia de la marcha, anomalías esqueléticas, almohadilla de grasa dorsocervical y cirrosis infantil. La morfología cerebral suele ser normal, aunque se han descrito casos de mielinización retardada e hipoplasia del tronco encefálico."},"it":{"name":"Sindrome microcefalia primitiva-disabilità intellettiva lieve-diabete ad esordio giovanile","definition":"La sindrome che associa la microcefalia primitiva, la disabilità intellettiva lieve e il diabete ad esordio giovanile è una malattia genetica rara da disabilità intellettiva, caratterizzata da microcefalia congenita persistente, scarso peso alla nascita, bassa statura, crisi epilettiche ad esordio infantile, ritardo dello sviluppo globale, lieve disabilità intellettiva e diabete mellito ad esordio nell'adolescenza o all'inizio della vita adulta. Può associarsi ad andatura atassica, anomalie scheletriche, presenza di un cuscinetto di grasso dorso-cervicale e cirrosi infantile. Di solito la morfologia del cervello è normale, sebbene siano stati descritti pazienti con ritardo della mielinizzazione ed ipoplasia del tronco encefalico."},"nl":{"name":"Primaire microcefalie - milde intellectuele achterstand - vroeg beginnende diabetes-syndroom","definition":"Primaire microcefalie - milde intellectuele achterstand - vroeg beginnende diabetes-syndroom is een zeldzame, genetische, syndromale stoornis met intellectuele beperking die wordt gekarakteriseerd door congenitale, persisterende microcefalie, laag geboortegewicht, kleine gestalte, aanvang in de kindertijd van insulten, algehele ontwikkelingsachterstand, milde intellectuele achterstand, en diabetes mellitus met aanvang in de adolescentie of jonge volwassenheid. Gangataxie, skeletanomalieën, dorsocervicaal vetkussen, en infantiele cirrose kunnen ook geassocieerd zijn. De morfologie van de hersenen is doorgaans normaal, hoewel vertraagde myelinisatie en hypoplastische hersenstam werden gerapporteerd."},"pt":{"name":"Síndrome de microcefalia primária-perturbação do desenvolvimento intelectual ligeira-diabetes com início precoce"},"pl":{"name":"Zespół małogłowie pierwotne-łagodna niepełnosprawność intelektualna-cukrzyca o początku w wieku młodzieńczym","definition":"*Zespół małogłowie pierwotne-łagodna niepełnosprawność intelektualna-cukrzyca o początku w wieku młodzieńczym jest rzadkim, genetycznie uwarunkowanym zespołem z niepełnosprawnością intelektualną, który charakteryzuje się wrodzonym, przetrwałym małogłowiem, niską masą urodzeniową, niskim wzrostem, napadami drgawkowymi o początku w dzieciństwie, całościowym opóźnieniem rozwoju, łagodną niepełnosprawnością intelektualną oraz cukrzycą ujawniającą się u nastolatków lub młodych dorosłych. Objawy towarzyszące to ataktyczny chód, nieprawidłowości kostne, gromadzenie się tkanki tłuszczowej w obrębie karku i szyi oraz marskość wątroby u niemowląt. Budowa mózgu jest zazwyczaj prawidłowa, chociaż opisywano opóźnienie mielinizacji i hipoplazją pniu mózgu."},"cs":{"name":"Syndrom zahrnující primární mikrocefalii, mírnou mentální retardaci a diabetes s nástupem v mládí"},"uk":{"name":"Синдром первинної мікроцефалії-легкої розумової відсталості-діабету в молодому віці","definition":"A rare, genetic, syndromic intellectual disability disorder characterized by congenital, persistent microcephaly, low birth weight, short stature, childhood-onset seizures, global development delay, mild intellectual disability, and adolescent or young adult-onset diabetes mellitus. Gait ataxia, skeletal abnormalities, dorsocervical fat pad, and infantile cirrhosis may also be associated. Brain morphology is typically normal, although delayed myelination and hypoplastic brainstem have been reported."},"zh":{"name":"原发性小头畸形-轻度智力障碍-青年起病糖尿病综合征","definition":"原发性小头畸形-轻度智力障碍-青年起病糖尿病综合征是一种罕见的遗传性综合智力残疾障碍，其特征是先天性、持续性小头畸形、出生体重低、身材矮小、儿童期起病的癫痫发作、全面发育迟缓、轻度智力障碍以及青少年或青年糖尿病。步态共济失调、骨骼异常、颈部背部脂肪垫和婴儿肝硬化也可能与本病相关。尽管有报道称会发生髓鞘形成延迟和脑干发育不良，但脑形态学是正常的。"},"tr":{"name":"Primer mikrosefali-hafif zihinsel yetersizlik-genç-başlangıçlı diyabet sendromu"}},"xrefs":[{"source":"OMIM","code":"616033","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"616817","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0018320","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5190597","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"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":181376,"name":"Rare diabetes mellitus type 2","classifications":[193]},{"orpha":183625,"name":"Rare genetic diabetes mellitus","classifications":[156]},{"orpha":269528,"name":"Syndrome with microcephaly as a major feature","classifications":[147,156,181]}],"children":[],"genes":[{"symbol":"PPP1R15B","name":"protein phosphatase 1 regulatory subunit 15B","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"26159176[PMID]_26307080[PMID]","hgnc":"14951","ensembl":"ENSG00000158615","omim":"613257","loci":["1q32.1"]},{"symbol":"TRMT10A","name":"tRNA methyltransferase 10A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"24204302[PMID]","hgnc":"28403","ensembl":"ENSG00000145331","omim":"616013","loci":["4q23"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Adolescent","Childhood"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":8.0,"area":"Worldwide","status":"Validated","source":"25053765[PMID]_26159176[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_25053765[PMID]_26159176[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-11-27","source":"26307080[PMID]_26159176[PMID]_26297882[PMID]_26526202[PMID]","terms":[{"hpo":"HP:0000819","label":"Diabetes mellitus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011451","label":"Primary microcephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003508","label":"Proportionate short stature","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001518","label":"Small for gestational age","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004325","label":"Decreased body weight","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000823","label":"Delayed puberty","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001943","label":"Hypoglycemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001620","label":"Abnormally high-pitched voice","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000592","label":"Blue sclerae","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001348","label":"Brisk reflexes","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002136","label":"Broad-based gait","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030084","label":"Clinodactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010344","label":"Deviation of the 5th toe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002460","label":"Distal muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025383","label":"Dorsocervical fat pad","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0200021","label":"Down-sloping shoulders","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002714","label":"Downturned corners of mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002213","label":"Fine hair","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000293","label":"Full cheeks","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000685","label":"Hypoplasia of teeth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002365","label":"Hypoplasia of the brainstem","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000601","label":"Hypotelorism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000821","label":"Hypothyroidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001946","label":"Ketosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002751","label":"Kyphoscoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000294","label":"Low anterior hairline","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000400","label":"Macrotia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000275","label":"Narrow face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000341","label":"Narrow forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000160","label":"Narrow mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000677","label":"Oligodontia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000767","label":"Pectus excavatum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008081","label":"Pes valgus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000311","label":"Round face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007258","label":"Severe demyelination of the white matter","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008850","label":"Severe postnatal growth retardation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003196","label":"Short nose","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000322","label":"Short philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001238","label":"Slender finger","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011308","label":"Slender toe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000274","label":"Small face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008070","label":"Sparse hair","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002313","label":"Spastic paraparesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000664","label":"Synophrys","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000219","label":"Thin upper lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000445","label":"Wide nose","frequency":"Occasional (29-5%)","criteria":null}]}}