Family studies of individuals with eyelid myoclonia with absences

PURPOSE: Eyelid myoclonia with absences (EM) is an uncommon type of absence seizure associated with a variety of epilepsy syndromes. The syndrome of epilepsy with EM (EMA) has been proposed to denote the onset of frequent EM induced by eye closure and photic stimulation beginning in childhood. The clinical genetics of EMA has not been well characterized, although a family history of seizures is not infrequent. METHODS: Individuals with EMA were ascertained by referral and through the investigators' clinical practices. All available family members were assessed for seizures using a validated seizure questionnaire. Electroclinical data were obtained on each proband and all affected family members; pedigrees were constructed. Families were analyzed for phenotypic patterns. KEY FINDINGS: Eighteen individuals with EMA were recruited. A history of seizures was found in 34 relatives in 15 (83%) of 18 families. In terms of epilepsy syndromes, 9 relatives from 7 of 15 families had febrile seizures. Two relatives had EMA. Classical genetic generalized epilepsy (GGE) syndromes were seen in five relatives: two generalized tonic-clonic seizures alone, two childhood absence epilepsy (CAE), and one juvenile myoclonic epilepsy (JME). Genetic epilepsy with febrile seizures plus (GEFS+) phenotypes occurred in 16 relatives. On review of the epilepsy syndromes within each family, seven families had a pattern consistent with GEFS+, whereas three families had classical GGE. SIGNIFICANCE: The clinical genetics of EMA is suggestive of complex inheritance with shared genetic determinants overlapping with both classical GGE and GEFS+. The epilepsy syndromes in relatives of probands with EMA differ from those found in families of probands with CAE, supporting the concept that patients with EMA have a syndrome that is distinct from CAE. This presumably reflects different genetic components contributing to their genetic architecture.