The genetics of epilepsy syndromes was studied by an evaluation of 253 twin pairs at the University of Melbourne, Australia. One or both twins had seizures, Among monozygous (MZ) and dizygous (DZ) twin pairs, 44% and 10% were concordant for seizures, respectively. Both twins had the same major epilepsy syndromes in 94% of concordant MZ pairs and 71% of concordant DZ pairs. The concordance rates for generalized epilepsies, both idiopathic and symptomatic, were greater than those for partial epilepsies. Febrile seizures and unclassified epilepsies had intermediate rates. Genetic factors play a role in all epilepsy syndromes but especially in generalized epilepsies. [1]

COMMENT. The authors conclude that genetics of epilepsy is syndrome-specific rather than a broad genetic predisposition. Their findings support those of Lennox WG who pioneered the research on genetics of epilepsy in twins in the early 1950s. I was privileged to be a Fellow in his “Seizure Clinic” at Harvard when he and a psychologist co-worker reported a series of 173 twin pairs [2]. Lennox not only found evidence for an “inherited epileptic predisposition” but he also demonstrated a “pattern-specific” genetic tendency, stronger in twins with generalized seizures (grand mal) than with partial seizures (psychomotor). “Grand mal appeared concordantly in 82% of monozygotic and in 15% of dizygotic twins.” “Concordance of psychomotor attacks was 38% in monozygotic pairs and 5% in the dizygotic.” In petit mal seizures, concordance was 75% among MZ twins and absent in DZ twins. Lennox also reported the concordance of 3 per sec spike-and-wave EEG dysrythmia in 16 of 19 MZ twin pairs and none of 14 DZ twin pairs.

Epilepsy phenotypes and genotypes of Angelman syndrome were compared in 20 patients at the University of California, Los Angeles, School of Medicine [3]. Patients were selected on clinical cytogenetic and molecular diagnosis of AS and all had characteristic EEGs with bifrontal and diffuse 1-3 Hz slow waves or slow and sharp waves. Maternally inherited chromosome 15q11-13 deletions were associated with severe intractable epilepsy, whereas UBE3A gene mutations and uniparental disomy occurred with mild epilepsy.