Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F16%3A10333454" target="_blank" >RIV/00064203:_____/16:10333454 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/16:10333454

Result on the web

<a href="http://dx.doi.org/10.1136/jmedgenet-2015-103451" target="_blank" >http://dx.doi.org/10.1136/jmedgenet-2015-103451</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1136/jmedgenet-2015-103451" target="_blank" >10.1136/jmedgenet-2015-103451</a>

Result language

angličtina

Original language name

Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy

Original language description

Objective We aimed to delineate the neurodevelopmental spectrum associated with SYNGAP1 mutations and to investigate genotype-phenotype correlations. Methods We sequenced the exome or screened the exons of SYNGAP1 in a total of 251 patients with neurodevelopmental disorders. Molecular and clinical data from patients with SYNGAP1 mutations from other centres were also collected, focusing on developmental aspects and the associated epilepsy phenotype. A review of SYNGAP1 mutations published in the literature was also performed. Results We describe 17 unrelated affected individuals carrying 13 different novel loss-of-function SYNGAP1 mutations. Developmental delay was the first manifestation of SYNGAP1-related encephalopathy; intellectual disability became progressively obvious and was associated with autistic behaviours in eight patients. Hypotonia and unstable gait were frequent associated neurological features. With the exception of one patient who experienced a single seizure, all patients had epilepsy, characterised by falls or head drops due to atonic or myoclonic seizures, (myoclonic) absences and/or eyelid myoclonia. Triggers of seizures were frequent (n=7). Seizures were pharmacoresistant in half of the patients. The severity of the epilepsy did not correlate with the presence of autistic features or with the severity of cognitive impairment. Mutations were distributed throughout the gene, but spared spliced 3' and 5' exons. Seizures in patients with mutations in exons 4-5 were more pharmacoresponsive than in patients with mutations in exons 8-15. Conclusions SYNGAP1 encephalopathy is characterised by early neurodevelopmental delay typically preceding the onset of a relatively recognisable epilepsy comprising generalised seizures (absences, myoclonic jerks) and frequent triggers.

Czech name

—

Czech description

—

Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

—

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Medical Genetics

ISSN

0022-2593

e-ISSN

—

Volume of the periodical

53

Issue of the periodical within the volume

8

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

511-522

UT code for WoS article

000380816700002

EID of the result in the Scopus database

2-s2.0-84981333011