TY - JOUR T1 - Genetic and neurodevelopmental spectrum of <em>SYNGAP1</em>-associated intellectual disability and epilepsy JF - Journal of Medical Genetics JO - J Med Genet SP - 511 LP - 522 DO - 10.1136/jmedgenet-2015-103451 VL - 53 IS - 8 AU - Cyril Mignot AU - Celina von Stülpnagel AU - Caroline Nava AU - Dorothée Ville AU - Damien Sanlaville AU - Gaetan Lesca AU - Agnès Rastetter AU - Benoit Gachet AU - Yannick Marie AU - G Christoph Korenke AU - Ingo Borggraefe AU - Dorota Hoffmann-Zacharska AU - Elżbieta Szczepanik AU - Mariola Rudzka-Dybała AU - Uluç Yiş AU - Hande Çağlayan AU - Arnaud Isapof AU - Isabelle Marey AU - Eleni Panagiotakaki AU - Christian Korff AU - Eva Rossier AU - Angelika Riess AU - Stefanie Beck-Woedl AU - Anita Rauch AU - Christiane Zweier AU - Juliane Hoyer AU - André Reis AU - Mikhail Mironov AU - Maria Bobylova AU - Konstantin Mukhin AU - Laura Hernandez-Hernandez AU - Bridget Maher AU - Sanjay Sisodiya AU - Marius Kuhn AU - Dieter Glaeser AU - Sarah Weckhuysen AU - Candace T Myers AU - Heather C Mefford AU - Konstanze Hörtnagel AU - Saskia Biskup AU - EuroEPINOMICS-RES MAE working group AU - Johannes R Lemke AU - Delphine Héron AU - Gerhard Kluger AU - Christel Depienne Y1 - 2016/08/01 UR - http://jmg.bmj.com/content/53/8/511.abstract N2 - 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. ER -