Summary: Purpose: Mutations of the α1 subunit sodium channel gene (SCN1A) cause severe myoclonic epilepsy of infancy (SMEI). Mutations of SCN1A have been found in 40 to 100% of SMEI patients and are de novo in the majority of individuals.
Methods: We studied two sisters with SMEI and their father with febrile seizures.
Results: SCN1A screening revealed a splice-site mutation in both sisters. The mutation was inherited from their father in whom, however, a mosaicism was found, with 37% of ectodermal derivative cells carrying the mutation.
Conclusions: In this family, a SCN1A mosaic mutation correlated with the milder phenotype, whereas the full heterozygous mutation caused SMEI. The possibility of mosaic mutations must, therefore, also be taken into account for genetic counseling and determining the recurrence risk in patients with SMEI.