Novel SCN1A and GABRA1 Gene Mutations With Diverse Phenotypic Features and the Question on the Existence of a Broader Spectrum of Dravet Syndrome:

摘要

In the light of modern molecular technologies, the understanding of the complexity of the numerous genotypea??phenotype correlations regarding Dravet syndrome is mandatory. Motivated by 2 patients, whose whole-exome sequencing revealed novel mutations that exemplify the phenotypic and genetic heterogeneities associated with typical and atypical Dravet syndrome presentations, the authors discuss the existence of a broader spectrum of Dravet syndrome. The first patient is a 4-year-old boy with fairly typical Dravet syndrome and a novel sodium channel ?±1 subunit gene mutation of high-predicted combined pathogenicity likelihood. The second patient is a 15-year-old boy with some atypical features of Dravet syndrome, harboring a novel mutation of the ?3-aminobutyric acid receptor ?±1 subunit gene, whose role in this syndrome pathogenesis has recently been highlighted. A brief review of the literature reveals that none of the current diagnostic criteria is thoroughly predictive of the disease, and phenotypic discrepancies are common among patients carrying atypical Dravet syndrome mutations. The authors conclude that the discussion of a Dravet syndrome spectrum is relevant.