INTRODUCTION

Dravet syndrome (DS) and variants are epileptic disorders of infancy and childhood associated with mutations in the SCN1A gene (1). There is no literature on such mutations in Indian patients with DS and related syndromes.

METHODS

Patients were recruited from a child neurology hospital-based clinic in a large city hospital in India both from a database and prospectively. Clinically suspected of DS and related conditions using standard clinical criteria, were offered genetic testing. Approval from the institutional review board was obtained and informed consent taken.  Direct sequencing using an automatic sequencer screened mutations in the SCN1A gene. Multiplex ligation-dependant probe amplification (MLPA) was performed on those with no mutations or only missense mutations. 100 healthy controls were also analysed.

RESULTS

A total of 86 patients were included. 13 DS, 27 severe myoclonic epilepsy of infancy borderline (SMEB), 13 GEFS+, 9 febrile seizures (FS) and 25 other intractable cryptogenic epilepsies. 41 patients with mutations were detected including 4 nonsense, 8 frame-shift, 4 splice-site and 18 missense  (7 were thought to be benign polymorphisms). 7 patients could not be analysed as information was incomplete. 14 mutations were novel.

Mutations were noted in 5/13 (38%) GEFS+, 16 /27 (59%) of SMEB and 13/13 (100%) of DS. There was no correlation found between different phenotypes and mutation types.

CONCLUSION

SCN1A mutations were frequently seen in Indian DS / SMEB patients and several of these were novel. Not unexpectedly no genotype phenotype correlation was found as has been reported earlier (2).