{"orpha":371364,"name":"Hypotonia-speech impairment-severe cognitive delay syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Infantile hypotonia-psychomotor retardation-characteristic facies syndrome","IHPRF syndrome"],"definition":"Hypotonia-speech impairment-severe cognitive delay syndrome is a rare, genetic neurodegenerative disorder characterized by severe, persistent hypotonia (presenting at birth or in early infancy), severe global developmental delay (with poor or absent speech, difficulty or inability to roll, sit or walk), profound intellectual disability, and failure to thrive. Additional manifestations include microcephaly, progressive peripheral spasticity, bilateral strabismus and nystagmus, constipation, and variable dysmorphic facial features (including plagiocephaly, broad forehead, small nose, low-set ears, micrognathia and open mouth with tented upper lip).","note":null,"url":"https://raremap.alftech.space/d/ORPHA-371364/","orphanet_url":"https://www.orpha.net/en/disease/detail/371364","names":{"fr":{"name":"Syndrome d'hypotonie-troubles du langage sévères-retard cognitif sévère","definition":"Le syndrome d'hypotonie-trouble sévère du langage-retard cognitif sévère est un trouble génétique neurodégénératif rare caractérisé par une hypotonie persistante sévère (apparaissant à la naissance ou pendant la petite enfance), un retard de développement global (langage pauvre ou absent, difficultés ou incapacité à se tourner, s'assoir ou marcher), un déficit intellectuel sévère et un retard de croissance staturo-pondérale. Les manifestations additionnelles incluent une microcéphalie, une spasticité périphérique progressive, un strabisme et un nystagmus bilatéraux, une constipation et une dysmorphie faciale variable (incluant une plagiocéphalie, un front large, un petit nez, des oreilles implantées basses, une micrognathie, et une bouche ouverte avec la lèvre supérieure en forme de tente)."},"de":{"name":"Hypotonie-Sprachstörung-schwere kognitive Entwicklungsverzögerung-Syndrom","synonyms":["IHPRF-Syndrom","Infantile Hypotonie mit psychomotorischer Entwicklungsverzögerung und charakteristischem Gesicht"],"definition":"Eine seltene, genetisch bedingte neurodegenerative Störung, die durch schwere, anhaltende Hypotonie (bei der Geburt oder im frühen Säuglingsalter), schwere globale Entwicklungsverzögerung (mit unzureichender oder fehlender Sprache, Schwierigkeiten oder Unfähigkeit zu rollen, zu sitzen oder zu gehen), schwere Intelligenzminderung und Gedeihstörung gekennzeichnet ist. Weitere Manifestationen sind Mikrozephalie, progressive periphere Spastik, bilaterales Schielen und Nystagmus, Verstopfung sowie variable dysmorphe Gesichtszüge (einschließlich Plagiozephalie, breite Stirn, kleine Nase, tief angesetzte Ohren, Mikrognathie und offener Mund mit gespannter Oberlippe)."},"es":{"name":"Síndrome de hipotonía-trastorno del habla-retraso cognitivo grave","synonyms":["Síndrome IHPRF","Síndrome de hipotonía infantil-retraso psicomotor-facies característica"],"definition":"El síndrome de hipotonía-trastorno del habla-retraso cognitivo grave es un trastorno genético neurodegenerativo poco frecuente caracterizado por hipotonía grave persistente (que se presenta al nacer o en la infancia temprana), retraso grave del desarrollo global (habla deficiente o ausente, dificultad o incapacidad para rodar, sentarse o caminar), discapacidad intelectual grave, y fallo de medro. Otras manifestaciones adicionales incluyen microcefalia, espasticidad progresiva, estrabismo bilateral y nistagmo, estreñimiento y rasgos faciales dismórficos variables (que incluyen plagiocefalia, frente ancha, nariz pequeña, orejas de implantación baja, micrognatia y boca abierta con el labio superior en forma de carpa)."},"it":{"name":"Ipotonia-deficit del linguaggio-ritardo cognitivo grave","definition":"La sindrome che associa ipotonia, deficit del linguaggio e ritardo cognitivo grave è una malattia neurodegenerativa genetica rara, caratterizzata da ipotonia persistente grave (che esordisce alla nascita o nel primo periodo neonatale), grave ritardo dello sviluppo globale (con assenza o importante riduzione del linguaggio, difficoltà o incapacità di rotolarsi, mettersi a sedere o camminare), grave disabilità intellettiva e ritardo della crescita. Altri segni clinici sono la microcefalia, la spasticità periferica progressiva, lo strabismo bilaterale e il nistagmo e i dismorfismi facciali di gravità variabile (plagiocefalia, fronte ampia, naso piccolo, orecchie a basso impianto, micrognazia e bocca con labbro superiore ''a tenda'')."},"nl":{"name":"Hypotonie - spraakstoornis - ernstige cognitieve achterstand-syndroom","synonyms":["IHPRF-syndroom","Infantiele hypotonie - psychomotorische achterstand - karakteristiek gelaat-syndroom"],"definition":"Hypotonie - spraakstoornis - ernstige cognitieve achterstand-syndroom is een zeldzame, genetische neurodegeneratieve stoornis die gekarakteriseerd wordt door ernstige en aanhoudende hypotonie (die aanvangt bij de geboorte of tijdens de zuigelingentijd), ernstige algemene ontwikkelingsachterstand (met povere of afwezige spraak, moeilijkheden met of niet in staat zijn om te rollen, zitten of stappen), ernstige intellectuele achterstand, en groeiachterstand. Bijkomende manifestaties zijn onder meer microcefalie, progressieve perifere spasticiteit, bilateraal strabisme en nystagmus, constipatie, en variabele dysmorfe gelaatskenmerken (waaronder plagiocefalie, breed voorhoofd, smalle neus, laagstaande oren, micrognathie en open mond met tentvormige bovenlip)."},"pt":{"name":"Síndrome de hipotonia-perturbação da linguagem-perturbação do desenvolvimento intelectual grave"},"pl":{"name":"Zespół hipotonii, upośledzenia mowy i ciężkiego opóźnienia rozwoju poznawczego","synonyms":["Zespół IHPRF","Zespół hipotonii niemowlęcej, opóźnienia psychruchowego i charakterystycznego wyglądu twarzy"]},"cs":{"name":"Syndrom zahrnující hypotonii, poruchu řeči a těžké kognitivní opoždění","synonyms":["Infantile hypotonia-psychomotor retardation-characteristic facies syndrome","IHPRF syndrome"]},"uk":{"name":"Синдром гіпотонії-порушення мовлення-тяжкої когнітивної затримки","synonyms":["Синдром IHPRF","Синдром дитячої гіпотонії - затримка психомоторного розвитку - фаціальний синдром"],"definition":"Hypotonia-speech impairment-severe cognitive delay syndrome is a rare, genetic neurodegenerative disorder characterized by severe, persistent hypotonia (presenting at birth or in early infancy), severe global developmental delay (with poor or absent speech, difficulty or inability to roll, sit or walk), profound intellectual disability, and failure to thrive. Additional manifestations include microcephaly, progressive peripheral spasticity, bilateral strabismus and nystagmus, constipation, and variable dysmorphic facial features (including plagiocephaly, broad forehead, small nose, low-set ears, micrognathia and open mouth with tented upper lip)."},"zh":{"name":"低张力-言语障碍-严重认知延迟综合征","synonyms":["IHPRF综合征"],"definition":"张力减退-言语损害-严重认知延迟综合征是一种罕见的遗传性神经退行性疾病，其特征是严重的持续性肌张力低(出生时或婴儿早期出现)，严重的全面发育延迟(言语不良或缺失，难以或无法翻滚、坐或走路)，极重度智力残疾和生长迟滞。本病的其他表现包括小头畸形、进行性外周痉挛、双侧斜视和眼球震颤、便秘和各种面部畸形(包括斜头畸形、宽额、小鼻子、低位耳、小颌畸形和张口伴薄上唇)。"},"tr":{"name":"Hipotoni-konuşma bozukluğu-ağır bilişsel gecikme sendromu","synonyms":["İnfantil hipotoni-psikomotor gerilik-karakteristik yüz sendromu","IHPRF sendromu"]}},"xrefs":[{"source":"OMIM","code":"615419","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"616801","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0014176","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4706556","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":183500,"name":"Genetic neurodegenerative disease","classifications":[156]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":182070,"name":"Rare neurodegenerative disease","classifications":[181]}],"children":[{"orpha":700336,"name":"Hypotonia-speech impairment-severe cognitive delay syndrome due to NALCN deficiency","type":"Clinical subtype"},{"orpha":700333,"name":"Hypotonia-speech impairment-severe cognitive delay syndrome due to UNC80 deficiency","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"UNC80","name":"unc-80 subunit of NALCN channel complex","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"26708751[PMID]_26708753[PMID]_26545877[PMID]","hgnc":"26582","ensembl":"ENSG00000144406","omim":"612636","loci":["2q34"],"via":{"orpha":700333,"name":"Hypotonia-speech impairment-severe cognitive delay syndrome due to UNC80 deficiency"}},{"symbol":"NALCN","name":"sodium leak channel, non-selective","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23749988[PMID]_24075186[PMID]","hgnc":"19082","ensembl":"ENSG00000102452","omim":"611549","loci":["13q32.3-q33.1"],"via":{"orpha":700336,"name":"Hypotonia-speech impairment-severe cognitive delay syndrome due to NALCN deficiency"}}],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Not yet validated","source":"23749988[PMID]_24075186[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-11-26","source":"27513830[PMID]_26545877[PMID]_26708753[PMID]_26708751[PMID]","terms":[{"hpo":"HP:0001344","label":"Absent speech","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000565","label":"Esotropia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008947","label":"Floppy infant","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0009884","label":"Tapered distal phalanges of finger","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001166","label":"Arachnodactyly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004326","label":"Cachexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002019","label":"Constipation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100660","label":"Dyskinesia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002353","label":"EEG abnormality","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009931","label":"Enlarged naris","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002007","label":"Frontal bossing","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100963","label":"Hyperesthesia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001319","label":"Neonatal hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001357","label":"Plagiocephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000426","label":"Prominent nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001525","label":"Severe failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000322","label":"Short philtrum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0200055","label":"Small hand","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000319","label":"Smooth philtrum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001762","label":"Talipes equinovarus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010804","label":"Tented upper lip vermilion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000219","label":"Thin upper lip vermilion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000325","label":"Triangular face","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100024","label":"Conspicuously happy disposition","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003458","label":"EMG: myopathic abnormalities","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002987","label":"Elbow flexion contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003273","label":"Hip contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006380","label":"Knee flexion contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011470","label":"Nasogastric tube feeding in infancy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002870","label":"Obstructive sleep apnea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100716","label":"Self-injurious behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002360","label":"Sleep abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002510","label":"Spastic tetraplegia","frequency":"Occasional (29-5%)","criteria":null}]}}