Objective: To identify cryptic chromosomal deletions involving SCN1A in patients with severe myoclonic epilepsy of infancy (SMEI).
Methods: Thirty-nine patients with SMEI and without SCN1A point mutations and their parents were typed with 14 intragenic SCN1A polymorphisms to identify hemizygosity. The parental origin and the extent of genomic deletions were determined by fluorescence in situ hybridization analysis using genomic clones encompassing chromosome 2q24.3-q31.1. Deletion breakpoints were more finely mapped by typing single-nucleotide polymorphisms and microsatellite markers.
Results: We identified three patients with SMEI who had genomic deletions encompassing the SCN1A locus. Deletion size was between 607 kb and 4.7 Mb. Deletions originated de novo from paternal chromosome in all subjects. One patient had central precocious puberty and palatoschisis. Genotype-phenotype correlations suggest that these clinical features are due to genes centromeric to SCN1A.
Conclusions: Patients with severe myoclonic epilepsy of infancy (SMEI) lacking SCN1A point mutations should be investigated for cryptic chromosomal deletions involving SCN1A. Clinical features other than epilepsy could be associated with SMEI as a consequence of deletions in contiguous genes.