RT Journal Article
SR Electronic
T1 Genetic and neurodevelopmental spectrum of <em>SYNGAP1</em>-associated intellectual disability and epilepsy
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 511
OP 522
DO 10.1136/jmedgenet-2015-103451
VO 53
IS 8
A1 Mignot, Cyril
A1 von Stülpnagel, Celina
A1 Nava, Caroline
A1 Ville, Dorothée
A1 Sanlaville, Damien
A1 Lesca, Gaetan
A1 Rastetter, Agnès
A1 Gachet, Benoit
A1 Marie, Yannick
A1 Korenke, G Christoph
A1 Borggraefe, Ingo
A1 Hoffmann-Zacharska, Dorota
A1 Szczepanik, Elżbieta
A1 Rudzka-Dybała, Mariola
A1 Yiş, Uluç
A1 Çağlayan, Hande
A1 Isapof, Arnaud
A1 Marey, Isabelle
A1 Panagiotakaki, Eleni
A1 Korff, Christian
A1 Rossier, Eva
A1 Riess, Angelika
A1 Beck-Woedl, Stefanie
A1 Rauch, Anita
A1 Zweier, Christiane
A1 Hoyer, Juliane
A1 Reis, André
A1 Mironov, Mikhail
A1 Bobylova, Maria
A1 Mukhin, Konstantin
A1 Hernandez-Hernandez, Laura
A1 Maher, Bridget
A1 Sisodiya, Sanjay
A1 Kuhn, Marius
A1 Glaeser, Dieter
A1 Weckhuysen, Sarah
A1 Myers, Candace T
A1 Mefford, Heather C
A1 Hörtnagel, Konstanze
A1 Biskup, Saskia
A1 ,
A1 Lemke, Johannes R
A1 Héron, Delphine
A1 Kluger, Gerhard
A1 Depienne, Christel
YR 2016
UL http://jmg.bmj.com/content/53/8/511.abstract
AB 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.