{"orpha":1627,"name":"Deletion 5q35 syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["Del (5)(q35)","Del (5)(qter)","Distal 5q deletion","Monosomy 5q35","Telomeric deletion 5q"],"definition":"Deletion 5q35 refers to the different congenital malformation syndromes resulting from deletions of variable extent of the terminal part of the long arm of chromosome 5 (5q), spanning the region from 5q35.1 to 5q35.3 . The most significant anomaly is a recurring deletion in 5q35.2 comprising the <i>NSD1</i> gene that causes Sotos syndrome that is characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and various degrees of learning difficulty. Subtelomeric deletions of the terminal 3.5 Mb region on 5q35.3 are very rare, characterized by prenatal lymphedema with increased nuchal translucency, pronounced muscular hypotonia in infancy, borderline intelligence, postnatal short stature due to growth hormone deficiency, and a variety of minor anomalies such as mildly bell-shaped chest, minor congenital heart defects and a distinct facial gestalt. Larger deletions including bands 5q35.1, 5q35.2 and 5q35.3 cause a more severe phenotype that associates severe developmental delay with microcephaly, and significant cardiac defects (e.g. atrial septal defect with/without atrioventricular conduction defects, Ebstein anomaly, tetralogy of Fallot) linked to haploinsufficiency of <i>NKX2.5</i> (5q35.1). Various combinations of signs may result from deletions of variable extent depending on the genes comprised in the deleted segment.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-1627/","orphanet_url":"https://www.orpha.net/en/disease/detail/1627","names":{"fr":{"name":"Syndrome de délétion 5q35","synonyms":["Del (5)(q35)","Del (5)(qter)","Délétion distale 5q","Délétion télomérique 5q","Monosomie 5q35"],"definition":"Une anomalie rare du développement embryonnaire résultant de délétions d'étendue variable de la partie terminale du bras long du chromosome 5 (5q), couvrant la région de 5q35.1 à 5q35.3. L'anomalie la plus importante est une suppression récurrente en 5q35.2 comprenant le gène <i>NSD1</i> qui provoque le syndrome de Sotos qui se caractérise par des caractéristiques cardinales incluant une croissance excessive pendant l'enfance, une macrocéphalie, une dysmorphie faciale distinctive et divers degrés de difficulté d'apprentissage. Les délétions subtelomériques de la région terminale de 3,5 Mb sur 5q35.3 sont très rares, caractérisées par un lymphoedème prénatal avec une translucidité nucale accrue, une hypotonie musculaire prononcée pendant la petite enfance, une intelligence limite, une petite taille postnatale due à un déficit en hormone de croissance et une variété d'anomalies mineures telles que comme une poitrine légèrement en forme de cloche, des malformations cardiaques congénitales mineures et une dysmorphie faciale distincte. Des suppressions plus importantes, y compris les bandes 5q35.1, 5q35.2 et 5q35.3, provoquent un phénotype plus sévère qui associe un retard de développement sévère à une microcéphalie et des défauts cardiaques importants (défaut septal auriculaire avec ou sans défauts de conduction auriculo-ventriculaire, anomalie d'Ebstein, tétralogie de Fallot) lié à l'haploinsuffisance de <i>NKX2.5</i> (5q35.1). Diverses combinaisons de signes cliniques peuvent être le résultat de suppressions d'étendue variable selon les gènes compris dans le segment supprimé."},"de":{"name":"Deletion 5q35","synonyms":["Monosomie 5q35","Telomere Deletion 5q","Del (5)(q35)","Del (5)(qter)","Distale Deletion 5q"]},"es":{"name":"Síndrome de deleción 5q35","synonyms":["Del (5)(q35)","Del (5)(qter)","Deleción terminal 5q","Monosomía 5q35"],"definition":"Hace referencia a los diferentes síndromes polimalformativos congénitos debidos a deleciones de extensión variable en la zona terminal del brazo largo del cromosoma 5 (5q), abarcando desde la región 5q35.1 hasta 5q35.3. La anomalía más significativa es una deleción recurrente en 5q35.2 que comprende el gen <i>NSD1</i> y que se conoce como síndrome de Sotos, cuyos rasgos principales incluyen hipercrecimiento en la infancia, macrocefalia, facies característica y diferentes grados de dificultad en el aprendizaje. Las deleciones subteloméricas de 3.5 Mb en la región terminal 5q35.3 son muy poco frecuentes y están caracterizadas por linfedema prenatal con aumento de la translucencia nucal, hipotonía muscular marcada en la infancia, inteligencia límite, talla baja postnatal por deficiencia de la hormona de crecimiento y varias anomalías menores, tales como un tórax en forma de campana, defectos cardíacos congénitos leves y una facies característica. Las deleciones más grandes, que incluyen las bandas 5q35.1, 5q35.2 y 5q35.3, causan un fenotipo más grave asociado a un marcado retraso psicomotor, con microcefalia y defectos cardíacos moderados-graves (p. ej., comunicación interauricular con/sin defectos de la conducción auriculoventricular, anomalía de Ebstein, o tetralogía de Fallot), todo ello debido a la haploinsuficiencia del gen <i>NKX2.5</i> (5q35.1). En función de los genes comprendidos en los segmentos delecionados (deleciones de extensión variable), se producen diferentes combinaciones de hallazgos clínicos."},"it":{"name":"Sindrome delezione 5q35","synonyms":["Del (5)(q35)","Del (5)(qter)","Delezione 5q distale","Delezione 5q telomerica","Monosomia 5q35"],"definition":"La delezione 5q35 comprende un gruppo di malformazioni congenite causate da delezioni di ampiezza variabile della parte terminale del braccio lungo del cromosoma 5 (5q), che vanno dalla regione 5q35.1 alla regione 5q35.3. L'aberrazione cromosomica più significativa è una delezione ricorrente nella regione 5q35.2, che comprende il gene NSD1 che causa la sindrome di Sotos, caratterizzata da segni clinici caratteristici come l'iperaccrescimento durante l'infanzia, la macrocefalia, la facies tipica e le difficoltà di apprendimento di gravità variabile. Le delezioni subtelomeriche della regione terminale 3.5 Mb, a livello della banda 5q35.3, sono molto rare e sono caratterizzate da linfedema prenatale associato ad un aumento della traslucenza nucale, ipotonia muscolare marcata durante l'infanzia, intelligenza borderline, bassa statura postnatale secondaria ad un difetto dell'ormone della crescita e altre anomalie più lievi (torace lievemente a campana, cardiopatie congenite lievi, facies caratteristica). Delezioni più ampie, che interessano le bande 5q35.1, 5q35.2 e 5q35.3, esitano in un quadro clinico più grave, caratterizzato da grave ritardo dello sviluppo, microcefalia e cardiopatie gravi (difetto del setto atriale con o senza anomalie della conduzione, anomalia di Ebstein, tetralogia di Fallot), secondarie all'aploinsufficienza di <i>NKX2.5</i> (5q35.1). Delezioni di ampiezza variabile esitano in quadri che associano diversi segni clinici, a seconda dei geni compresi nel segmento deleto."},"nl":{"name":"Deletie 5q35-syndroom","synonyms":["Del (5)(q35)","Del (5)(qter)","Distale 5q deletie","Monosomie 5q35","Telomerische deletie 5q"],"definition":"Deletie 5q35 verwijst naar de verschillende congenitale malformatiesyndromen die het gevolg zijn van deleties met een variabele omvang van het uiteinde van de lange arm van chromosoom 5 (5q), dat de regio van 5q35.1 tot 5q35.3 omvat. De meest significante anomalie is een terugkerende deletie in 5q35.2, met inbegrip van het gen <i>NSD1</i>, die syndroom van Sotos veroorzaakt. Syndroom van Sotos wordt gekarakteriseerd door hoofdkenmerken als overmatige groei in de kindertijd, macrocefalie, typische gelaatsvorm, en variabele gradaties van leerproblemen. Subtelomerische deleties van de terminale 3,5Mb-regio op 5q35.3 zijn zeer zeldzaam, en worden gekarakteriseerd door prenataal lymfoedeem met verdikte nekplooi, uitgesproken spierhypotonie in de zuigelingentijd, intelligentie in het grensgebied, postnatale kleine gestalte door deficiëntie van groeihormoon, en een waaier aan kleine anomalieën zoals mild klokvormige borstkas, kleine congenitale hartdefecten, en een typische gelaatsvorm. Grotere deleties die de banden 5q35.1, 5q35.2 en 5q35.3 omvatten, veroorzaken een ernstiger fenotype dat ernstige ontwikkelingsachterstand associeert met microcefalie, alsook significante hartdefecten (e.g. atriumseptumdefect met/zonder atrioventriculaire geleidingsdefecten, anomalie van Ebstein, tetralogie van Fallot) gekoppeld aan haploinsufficiëntie van <i>NKX2.5</i> (5q35.1). Deleties met een variabele omvang kunnen aanleiding geven tot verscheidene combinaties van tekenen, afhankelijk van de genen die deel uitmaken van het verwijderde segment."},"pt":{"name":"Síndrome de deleção 5q35","synonyms":["Monossomia 5q35"],"definition":"A deleção 5q35 refere-se aos diferentes síndromes de malformação congénita resultantes de deleções de extensão variável na porção terminal do braço longo do cromossoma 5 (5q), abrangendo a região de 5q35.1 a 5q35.3. A anomalia mais significativa é uma deleção recorrente em 5q35.2, que compreende o gene NSD1 e causa a síndrome Sotos, caracterizada por características cardinais que incluem crescimento excessivo durante a infância, macrocefalia, fisionomia facial distinta e vários graus de dificuldades de aprendizagem. As deleções subteloméricas da região terminal de 3,5 Mb em 5q35.3 são muito raras, caracterizadas por linfedema pré-natal com aumento da translucência nucal, hipotonia muscular pronunciada na infância, inteligência limítrofe, baixa estatura pós-natal devido a deficiência de hormona de crescimento e uma variedade de anomalias menores, como tórax ligeiramente em forma de sino, cardiopatias congénitas menores e fisionomia facial distinta. Deleções maiores, incluindo as bandas 5q35.1, 5q35.2 e 5q35.3, causam um fenótipo mais grave, associado a um atraso grave do desenvolvimento com microcefalia e defeitos cardíacos significativos (por exemplo, comunicação interatrial com ou sem defeitos de condução auriculoventricular, anomalia Ebstein, tetralogia Fallot) ligados à haploinsuficiência de NKX2.5 (5q35.1). Diversas combinações de sinais podem resultar de deleções de extensão variável, dependendo dos genes incluídos no segmento delecionado."},"pl":{"name":"Zespół delecji 5q35","synonyms":["Del (5)(q35)","Del (5)(qter)","Dystalna delecja 5q","Monosomia 5q35","Telomerowa delecja 5q"]},"cs":{"name":"Delece 5q35","synonyms":["Del (5)(q35)","Del (5)(qter)","Distální 5q delece","Monozomie 5q35","Telomerická delece 5q"]},"uk":{"name":"Делеція 5q35","synonyms":["Del (5)(q35)","Del (5)(qter)","Дистальна делеція 5q","Моносомія 5q35","Делеція теломерної ділянки 5q"],"definition":"Deletion 5q35 refers to the different congenital malformation syndromes resulting from deletions of variable extent of the terminal part of the long arm of chromosome 5 (5q), spanning the region from 5q35.1 to 5q35.3 . The most significant anomaly is a recurring deletion in 5q35.2 comprising the <i>NSD1</i> gene that causes Sotos syndrome that is characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and various degrees of learning difficulty. Subtelomeric deletions of the terminal 3.5 Mb region on 5q35.3 are very rare, characterized by prenatal lymphedema with increased nuchal translucency, pronounced muscular hypotonia in infancy, borderline intelligence, postnatal short stature due to growth hormone deficiency, and a variety of minor anomalies such as mildly bell-shaped chest, minor congenital heart defects and a distinct facial gestalt. Larger deletions including bands 5q35.1, 5q35.2 and 5q35.3 cause a more severe phenotype that associates severe developmental delay with microcephaly, and significant cardiac defects (e.g. atrial septal defect with/without atrioventricular conduction defects, Ebstein anomaly, tetralogy of Fallot) linked to haploinsufficiency of <i>NKX2.5</i> (5q35.1). Various combinations of signs may result from deletions of variable extent depending on the genes comprised in the deleted segment."},"zh":{"name":"5q35缺失","synonyms":["5号染色体长臂末端着丝粒缺失"]},"tr":{"name":"Delesyon 5q35","synonyms":["Del(5)(q35)","Del(5)(qter)","Monozomi 5q35","Distal 5q delesyonu","Telomerik delesyon 5q"]}},"xrefs":[{"source":"ICD-10","code":"Q93.5","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD44.50","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1254440453"},{"source":"MONDO","code":"0015571","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C537647","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C2931574","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":262038,"name":"Partial deletion of the long arm of chromosome 5 syndrome","classifications":[147,156]}],"children":[],"genes":[{"symbol":"NKX2-5","name":"NK2 homeobox 5","gene_type":"gene with protein product","association":"Role in the phenotype of","status":"Assessed","source":"17910075[PMID]","hgnc":"2488","ensembl":"ENSG00000183072","omim":"600584","loci":["5q35.1"]},{"symbol":"NSD1","name":"nuclear receptor binding SET domain protein 1","gene_type":"gene with protein product","association":"Role in the phenotype of","status":"Assessed","source":"17910075[PMID]","hgnc":"14234","ensembl":"ENSG00000165671","omim":"606681","loci":["5q35.3"]}],"genes_via_subtypes":[],"inheritance":["Not applicable","Unknown"],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":10.0,"area":"Worldwide","status":"Validated","source":"11562936[PMID]_[EXPERT]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2024-12-11","source":"12900893[PMID]_17910075[PMID]","terms":[{"hpo":"HP:0001627","label":"Abnormal heart morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001531","label":"Failure to thrive in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002557","label":"Hypoplastic nipples","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010880","label":"Increased nuchal translucency","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002751","label":"Kyphoscoliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000239","label":"Large fontanelles","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000256","label":"Macrocephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000768","label":"Pectus carinatum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008897","label":"Postnatal growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Frequent (79-30%)","criteria":null}]}}