Format

Send to

Choose Destination
Epilepsia. 2015 Dec;56(12):1931-40. doi: 10.1111/epi.13214. Epub 2015 Oct 29.

Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases.

Author information

1
Pediatric Neurology Department, Timone Children Hospital, Marseille, France.
2
INSERM, U1028, CNRS, UMR5292, Laboratory of Molecular Genetics, Lyon, France.
3
Aix Marseille University, INSERM, UMR_S 910, Marseille, France.
4
Medical Genetics Department, Timone Children Hospital, Marseille, France.
5
Aix Marseille University, GMGF, Marseille, France.
6
Department of Pediatrics, St. Jacques Hospital, Besançon, France.
7
Pediatric Neurology Department, Montpellier University Hospital, Montpellier, France.
8
Institute for Neurosciences of Montpellier (INM), INSERM U 1051, Montpellier, France.
9
Pediatric Neurology Department, Trousseau Hospital, AP-HP, Paris, France.
10
Medical Genetics Department, Nantes University Hospital, Nantes, France.
11
Department of Pediatrics, Nantes University Hospital, Nantes, France.
12
Pediatric Neurology Department, Bordeaux University Hospital, Bordeaux, France.
13
Pediatric Neurology Department, Toulouse University Hospital, Toulouse, France.
14
Pediatric Neurology Department, Bicêtre Hospital, Kremlin-Bicêtre, France.
15
Department of Pediatrics, Limoges University Hospital, Limoges, France.
16
Department of Pediatrics, Dijon University Hospital, Dijon, France.
17
Pediatric Neurology Department, Lyon University Hospital, Bron, France.
18
Medical Genetics Department, St Etienne University Hospital, Saint Priez en Jarez, France.
19
Pediatric Neurology Department, Hautepierre Hospital, Strasbourg University Hospital, Strasbourg, France.
20
Pediatric Intensive Cares Unit, Hautepierre Hospital, Strasbourg University Hospital, Strasbourg, France.
21
Pediatric Neurology Department, Lille University Hospital, Lille, France.

Abstract

OBJECTIVE:

Mutations in the syntaxin binding protein 1 gene (STXBP1) have been associated mostly with early onset epileptic encephalopathies (EOEEs) and Ohtahara syndrome, with a mutation detection rate of approximately 10%, depending on the criteria of selection of patients. The aim of this study was to retrospectively describe clinical and electroencephalography (EEG) features associated with STXBP1-related epilepsies to orient molecular screening.

METHODS:

We screened STXBP1 in a cohort of 284 patients with epilepsy associated with a developmental delay/intellectual disability and brain magnetic resonance imaging (MRI) without any obvious structural abnormality. We reported on patients with a mutation and a microdeletion involving STXBP1 found using array comparative genomic hybridization (CGH).

RESULTS:

We found a mutation of STXBP1 in 22 patients and included 2 additional patients with a deletion including STXBP1. In 22 of them, epilepsy onset was before 3 months of age. EEG at onset was abnormal in all patients, suppression-burst and multifocal abnormalities being the most common patterns. The rate of patients carrying a mutation ranged from 25% in Ohtahara syndrome to <5% in patients with an epilepsy beginning after 3 months of age. Epilepsy improved over time for most patients, with an evolution to West syndrome in half. Patients had moderate to severe developmental delay with normal head growth. Cerebellar syndrome with ataxic gait and/or tremor was present in 60%.

SIGNIFICANCE:

Our data confirm that STXBP1 mutations are associated with neonatal-infantile epileptic encephalopathies. The initial key features highlighted in the cohort of early epileptic patients are motor seizures either focal or generalized, abnormal initial interictal EEG, and normal head growth. In addition, we constantly found an ongoing moderate to severe developmental delay with normal head growth. Patients often had ongoing ataxic gait with trembling gestures. Altogether these features should help the clinician to consider STXBP1 molecular screening.

KEYWORDS:

Early onset epileptic encephalopathy; Genetics; Ohtahara syndrome; Suppression-burst

PMID:
26514728
DOI:
10.1111/epi.13214
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center