Neonatal Onset of Epilepsy of Infancy with Migrating Focal Seizures Associated with a Novel GABRB3 Variant in Monozygotic Twins.

Background: Recently, a study providing insight into mutational spectrum was published (Møller et al 2017). The authors report considerable pleiotropy even for single mutations and were not able to identify any genotype-phenotype correlations.

Methods: The proband (twin B) was referred for massively parallel sequencing of epilepsy-related gene panel because of hypotonia and neonatal seizures. The revealed variant was confirmed with Sanger sequencing in the proband and the twin A, and both parents were tested for the presence of the variant.

Results: We report a case of epilepsy of infancy with migrating focal seizures (EIMFS) of neonatal onset in monozygotic twins with a de novo novel variant p.Thr281Ala. The variant has a uniform presentation on an identical genomic background. In addition, early seizure-onset epilepsy associated with mutation has been until now described only for the p.Leu256Gln variant in the (Møller et al 2017, Myers et al 2016) located in the transmembrane domain just as the p.Thr281Ala variant described here.

Conclusion: De novo mutations may cause neonatal-onset EIMFS with early-onset hypotonia, respiratory distress, and severe developmental delay.