Mignot, C;
Von Stülpnagel, C;
Nava, C;
Ville, D;
Sanlaville, D;
Lesca, G;
Rastetter, A;
... Depienne, C; + view all
(2016)
Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy.
Journal of Medical Genetics
, 53
(8)
pp. 511-522.
10.1136/jmedgenet-2015-103451.
Preview |
Text
Sisodiya_Mignot_2016_Genetic_and_extracted.pdf Download (1MB) | Preview |
Abstract
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.
| Type: | Article |
|---|---|
| Title: | Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1136/jmedgenet-2015-103451 |
| Publisher version: | http://dx.doi.org/10.1136/jmedgenet-2015-103451 |
| Language: | English |
| Additional information: | This article has been accepted for publication in the Journal of Medical Genetics following peer review. The definitive copyedited, typeset version, Mignot, C; Von Stülpnagel, C; Nava, C; Ville, D; Sanlaville, D; Lesca, G; Rastetter, A; (2016) Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy, Journal of Medical Genetics, is available online at: http://jmg.bmj.com/content/early/2016/03/17/jmedgenet-2015-103451. |
| Keywords: | Epilepsy and seizures, Genetics, Neurology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1483524 |
Archive Staff Only
 |
View Item |
