SCN1A Gene Mutation and Adaptive Functioning in 18 Vietnamese Children with Dravet Syndrome

Abstract

Background and PurposeDravet syndrome is a rare and severe type of epilepsy in infants. The heterogeneity in the overall intellectual disability that these patients suffer from has been attributed to differences in genetic background and epilepsy severity.MethodsEighteen Vietnamese children diagnosed with Dravet syndrome were included in this study. SCN1A variants were screened by direct sequencing and multiplex ligation-dependent probe amplification. Adaptive functioning was assessed in all patients using the Vietnamese version of the Vineland Adaptive Behavior Scales, and the results were analyzed relative to the SCN1A variants and epilepsy severity.ResultsWe identified 13 pathogenic or likely pathogenic variants, including 6 that have not been reported previously. We found no correlations between the presence or type of SCN1A variants and the level of adaptive functioning impairment or severity of epilepsy. Only two of nine patients aged at least 5 years had an adaptive functioning score higher than 50. Both of these patients had a low frequency of convulsive seizures and no history of status epilepticus or prolonged seizures. The remaining seven had very low adaptive functioning scores (39 or less) despite the variability in the severity of their epilepsy confirming the involvement of factors other than the severity of epilepsy in determining the developmental outcome.ConclusionsOur study expands the spectrum of known SCN1A variants and confirms the current understanding of the role of the genetic background and epilepsy severity in determining the developmental outcome of Dravet syndrome patients.

In vivo, in vitro and in silico correlations of four de novo SCN1A missense mutations

“…Additionally, we administered the VABS test which, unlike other IQ or DQ tests, allows comparison of adaptive daily functions at different ages, irrespective of developmental level and cooperation. VABS has previously been used in two studies assessing cognition and behavior in children with Dravet [48, 49]. This type of assessment suggested a distinctive profile for these children, with higher scores on the socialization domain, as compared to communication or living skills.…”

Progressive Worsening of Gait and Motor Abnormalities in Older Adults With Dravet Syndrome

“…As such, it is not surprising that, in addition to seizures, patients also have slowing of cognitive development and gait problems. 2,7 Relative to the pediatric population, there is limited information about DS in adults. [8][9][10][11][12] The majority of patients continue to have refractory seizures as adults, although their convulsive seizures can be restricted to sleep periods.…”

“…As such, it is not surprising that, in addition to seizures, patients also have slowing of cognitive development and gait problems. 2,7…”

SCN1B and SCN2B gene variants analysis in dravet syndrome patients

“…[1,2,6] We screened 48 DS patients and found 26 DS patients (54.2%) had SCN1A variants (Table S1), which were also reported in previous studies and database. [30–32] Studies reported causative variants of SCN1B p.R125C in two infants with DS [8,10] and SCN1B p.lle106Phe in one of 67 DS patients. [9] In order to find the pathogenesis of DS except SCN1A variants, we carried out this study to investigate the variants of SCN1B and SCN2B variants in DS patients.…”