Abstracts

Rationale: Myoclonic-Astatic Epilepsy (MAE, Doose Syndrome) is a severe childhood epilepsy syndrome characterized by myoclonic, atonic, generalized tonic-clonic, and/or absence seizures in previously normal children with a typical onset between 2 and 5 years. MAE is generally regarded as a disorder with polygenic inheritance. The occurrence of two patients with MAE in one pedigree is quite unusual. The genetic determinants predisposing for MAE are unknown. Mutations in SCN1A and GABRG2 have been reported in rare patients, but these mutations do not account for the majority of cases. Methods: Three consanguineous Arab families were ascertained through a proband with MAE as part of an ongoing study into the genetic basis of familial epilepsy in Israel and the Palestinian territories. Patients underwent detailed clinical analysis. Personal and family history as well as EEG recordings were obtained on all patients. Results: Pedigree analysis of three consanguineous families with MAE revealed a horizontal mode of inheritance, suggestive of autosomal recessive inheritance, with 6/14 siblings affected in Family 1, 5/12 siblings affected in Family 2, and two affected cousins in Family 3. All affected individuals have MAE and were the product of consanguineous unions. In Family 1, one additional cousin, also the product of a consanguineous union, had a generalised seizure disorder consistent with Idiopathic Generalized Epilepsy (IGE). In Family 2, the father had a seizure disorder consistent with Juvenile Myoclonic Epilepsy, and two more individuals in the family had a benign unclassified generalized epilepsy syndrome.Conclusions: Although MAE is regarded as a disorder with polygenic inheritance, these data raise the possibility of autosomal recessive inheritance, at least in some families. These findings may be relevant to the majority of sporadic MAE cases from smaller families. The presence of milder phenotypes within the IGE spectrum in relatives suggests that heterozygosity for the putative MAE locus might constitute a susceptibility factor for IGE. Further study of these and similar families may lead to the identification of genes in this severe childhood epilepsy syndrome. This work was supported by a grant from the Australian National Health and Medical Research Council.