PT  - JOURNAL ARTICLE
AU  - Mignot, Cyril
AU  - von Stülpnagel, Celina
AU  - Nava, Caroline
AU  - Ville, Dorothée
AU  - Sanlaville, Damien
AU  - Lesca, Gaetan
AU  - Rastetter, Agnès
AU  - Gachet, Benoit
AU  - Marie, Yannick
AU  - Korenke, G Christoph
AU  - Borggraefe, Ingo
AU  - Hoffmann-Zacharska, Dorota
AU  - Szczepanik, Elżbieta
AU  - Rudzka-Dybała, Mariola
AU  - Yiş, Uluç
AU  - Çağlayan, Hande
AU  - Isapof, Arnaud
AU  - Marey, Isabelle
AU  - Panagiotakaki, Eleni
AU  - Korff, Christian
AU  - Rossier, Eva
AU  - Riess, Angelika
AU  - Beck-Woedl, Stefanie
AU  - Rauch, Anita
AU  - Zweier, Christiane
AU  - Hoyer, Juliane
AU  - Reis, André
AU  - Mironov, Mikhail
AU  - Bobylova, Maria
AU  - Mukhin, Konstantin
AU  - Hernandez-Hernandez, Laura
AU  - Maher, Bridget
AU  - Sisodiya, Sanjay
AU  - Kuhn, Marius
AU  - Glaeser, Dieter
AU  - Weckhuysen, Sarah
AU  - Myers, Candace T
AU  - Mefford, Heather C
AU  - Hörtnagel, Konstanze
AU  - Biskup, Saskia
AU  - , 
AU  - Lemke, Johannes R
AU  - Héron, Delphine
AU  - Kluger, Gerhard
AU  - Depienne, Christel
TI  - Genetic and neurodevelopmental spectrum of <em>SYNGAP1</em>-associated intellectual disability and epilepsy
AID  - 10.1136/jmedgenet-2015-103451
DP  - 2016 Aug 01
TA  - Journal of Medical Genetics
PG  - 511--522
VI  - 53
IP  - 8
4099  - http://jmg.bmj.com/content/53/8/511.short
4100  - http://jmg.bmj.com/content/53/8/511.full
SO  - J Med Genet2016 Aug 01; 53
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.