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Neurology. 2013 Oct 15;81(16):1434-40. doi: 10.1212/WNL.0b013e3182a84163. Epub 2013 Sep 18.

Duplications of 17q12 can cause familial fever-related epilepsy syndromes.

Author information

1
From the Neurogenetics Group (K.H., S.W., P.H., P.D.J., A.S.), Department of Molecular Genetics, VIB, Antwerp; Laboratory of Neurogenetics (K.H., S.W., P.H., P.D.J., A.S.), Institute Born-Bunge, University of Antwerp; Department of Neurology (E.P., W.V.P.), University Hospital Gasthuisberg, Leuven; Center for Human Genetics (H.V.E.), University Hospitals Leuven, KU Leuven; and Division of Neurology (P.D.J.), Antwerp University Hospital, Antwerp, Belgium.

Abstract

OBJECTIVES:

After we identified a 17q12 duplication cosegregating in a 4-generation family with genetic or generalized epilepsy with febrile seizures plus (GEFS+), we aimed to determine the frequency of 17q12 genomic rearrangements in GEFS+ and a wide spectrum of other epilepsy phenotypes. We furthermore describe seizure prevalence in previously reported patients with a 17q12 duplication or deletion.

METHODS:

We analyzed 433 patients with a broad range of epilepsy phenotypes. The 180k Cytosure ISCA v2 array was used for copy number variation screening in the index patient. Segregation analysis and follow-up studies were performed with the multiplex amplicon quantification technique.

RESULTS:

We identified 2 families in which a 17q12 duplication segregated with febrile-sensitive epilepsy. In the follow-up study, the mutation rate in familial febrile seizures (FS) and GEFS+ phenotypes was 1/222. No 17q12 deletions were detected. Two of the 6 mutation carriers in the initial GEFS+ family had mild intellectual disability, whereas all family members of the second family were of normal intelligence. In the literature, 4 of 43 individuals with a 17q12 duplication and 4 of 55 with the reciprocal deletion were described to have had seizures.

CONCLUSIONS:

Our study shows that 17q12 duplications are a rare cause of familial FS and GEFS+. Although some family members might have intellectual disability, seizures can be the sole clinical symptom. This is the first report on an inherited copy number variation in these self-limiting fever-sensitive epilepsy syndromes, potentially revealing a novel pathomechanism involved in familial FS and GEFS+.

PMID:
24049133
DOI:
10.1212/WNL.0b013e3182a84163
[Indexed for MEDLINE]

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