SCN1A clinical spectrum includes the self-limited focal epilepsies of childhood
- Author(s)
- Kivity, S; Oliver, KL; Afawi, Z; Damiano, JA; Arsov, T; Bahlo, M; Berkovic, SF;
- Journal Title
- Epilepsy Res
- Publication Type
- Journal Article
- Abstract
- INTRODUCTION: Amongst autosomal dominant genetic epilepsy with febrile seizures plus (GEFS+) families, SCN1A variants are the most common genetic cause. Initially regarded as a generalized form of epilepsy, the GEFS+ spectrum is now known to include some focal epilepsies, but it is generally not conceptualized as extending to the self-limited focal epilepsies of childhood, such as Panayiotopoulos syndrome. There are, however, three reports of SCN1A variants in Panayiotopoulos syndrome. We describe the variable clinical phenotypes that include the self-limited focal epilepsies of childhood, present in a large GEFS+ family, segregating a heterozygous SCN1A missense variant. MATERIAL AND METHODS: Electro-clinical details on all putatively affected family members were sought and blood samples were taken for genetic analysis. Two individuals were chosen for SCN1A testing. All 26 exons and exon-intron junctions were amplified, sequenced and analyzed. This was followed by pedigree segregation analysis of the variant identified. RESULTS: A pathogenic heterozygous SCN1A (c.2624C>A; p.Thr875Lys) variant was identified. Sixteen of the 18 variant positive family members were affected (88% penetrance): 8 with febrile seizures, 2 febrile seizures plus, 1 unclassified seizures and 5 with self-limited focal epilepsy of childhood. Of these, one was diagnosed with atypical childhood epilepsy with centrotemporal spikes and four with Panayiotopoulos syndrome. DISCUSSION: By characterizing the heterogeneous clinical phenotypes in a large, SCN1A mutation positive GEFS+ family, we conclude that the GEFS+ spectrum can extend to the self-limited focal epilepsies of childhood, including Panayiotopoulos syndrome, and in turn highlight the complex genotype-phenotype correlations associated with SCN1A-related epilepsies.
- Publisher
- Elsevier
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 28192756
- Publisher's Version
- https://doi.org/10.1016/j.eplepsyres.2017.01.012
- NHMRC Grants
- NHMRC/1054618, NHMRC/1102971,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2017-04-06 09:27:35
Last Modified: 2017-04-07 03:25:54