The Molecular Genetics of the Benign Epilepsies of Infancy

Abstract

Three benign epilepsy syndromes with autosomal dominant inheritance are recognised in infancy. These are Benign Familial Neonatal Epilepsy (BFNE), Benign Familial NeonatalInfantile Epilepsy (BFNIE) and Benign Familial Infantile Epilepsy (BFIE). These disorders were previously known as Benign Familial Neonatal Seizures, Benign Familial NeonatalInfantile Seizures and Benign Familial Infantile Seizures, respectively (Berg et al., 2010). They were recently renamed by the International League Against Epilepsy Classification Committee. The three disorders differ in their average ages of onset but age of onset distributions overlap between the syndromes. Ages of onset vary within syndromes and within families affected with any of the syndromes. BFNE patients have lateralised motor seizures with a mean age of onset of around 3 days of age and a mean age of seizure offset of 3 months of age. Subsequent neurological development usually proceeds normally. However, about 15% of patients have later seizures or epilepsy and occasional cases deteriorate into severe epileptic encephalopathies with intellectual disability (Dedek et al., 2003; Borgatti et al., 2004; Steinlein et al., 2007). The benign form of the disorder was originally described in an Austrian family by Rett and Teubel (1964). Since then numerous BFNE families have been described, many with potassium channel subunit mutations, to provide a well established range of presentations. BFIE was originally described by Watanabe and colleagues in 1987, and is sometimes referred to as Watanabe syndrome. Watanabe observed that a subgroup of infants with generalised motor seizures had subsequent normal development and became seizure-free by 3 years of age. Similar families were subsequently described by Vigevano and colleagues (1992). Onset of seizures in BFIE occurs between 4 and 6 months of age with seizure offset generally occurring by 12 months of age. Seizures are generally not seen in later life. However, some cases develop paroxysmal dyskinesia or paroxysmal kinesigenic choreoathetosis in adolescence. This is known as infantile convulsions and choreoathetosis (ICCA) syndrome. BFNIE patients have similar seizures to those seen in BFNE and BFIE, with the average age of onset intermediate between the other two. Although BFNIE differs from these disorders in the average age of seizure onset, the age of onset distribution which can range within a single family from 3 days up to 13 months of age (Herlenius et al., 2007), significantly