Copy number variation in genetic epilepsy with febrile seizures plus

Genetic epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome in which affected individuals may have a variety of epilepsy phenotypes, the most common being febrile seizures (FS) and febrile seizures plus (FS+). We investigated the possible contribution of copy number variation to GEFS+.

We searched our epilepsy research database for patients in GEFS + families who underwent chromosomal microarray analysis. We reviewed the clinical features and results of genetic testing in these families.

Of twelve families with available microarray data, four had at least one copy number variant (CNV) identified. In Family 1, the proband had a maternally-inherited 15q11.2 deletion. In Family 5, four different CNVs were identified, variably present in the affected individuals; this included a 19p13.3 deletion affecting CACNA1A. Finally, in both Families 9 and 10, the proband had Dravet syndrome with pathogenic SCN1A variant, as well as a CNV (10q11.22 duplication in Family 9 and 22q11.2 deletion in Family 10).

The significance of these specific variants is difficult to precisely determine; however, there appeared to be an overrepresentation of CNVs in this small cohort. These findings suggest chromosomal microarray analysis could have clinical utility as part of the workup in GEFS + families.