Ten novel mutations of SCN1A were found in in a pair of monozygotic twins and 12 unrelated Japanese infants with severe myoclonic epilepsy in infancy (SMEI) examined at the Brain Science Institute, Saitama; and National Epilepsy Center, Shizuoko, Japan. Of the 10 heterozygous mutations, 3 were frameshift and 7 nonsense mutations. These rather than missense mutations are the major causes of SMEI. Missense mutations of the same gene result in generalized epilepsy with febrile sezures plus (GEFS plus). [1]
COMMENT. The syndrome of severe myoclonic epilepsy in infancy is characterized by normal development initially, onset of seizures during the first year, beginning with generalized or unilateral febrile clonic seizures, and followed by the secondary appearance of myoclonic seizures and partial seizures that are intractable and complicated by ataxia and mental deterioration. Genetic predisposition suggested by family history and concordant disease in monozygotic twins appears to be based on frameshift and nonsense mutations in the SCN1A gene.