Epilepsy, Familial Temporal Lobe, 4

For a general phenotypic description and a discussion of genetic heterogeneity of familial temporal lobe epilepsy, see 600512.

Clinical Features

Deprez et al. (2007) reported a 5-generation Belgian family with dominantly inherited occipitotemporal lobe epilepsy and migraine with visual aura. Age at onset ranged from childhood to adulthood. A total of 14 individuals were affected. Ten individuals had occipitotemporal lobe epilepsy, 5 of whom also had migraine with aura. Nine of the 10 patients had simple partial seizures with visual symptoms being most common (60%), followed by cognitive (50%), autonomic (50%), motor (50%), and somatosensory (20%) symptoms and olfactory (40%) and auditory (20%) hallucinations. None had deja vu. Three of the 10 patients had complex partial seizures, and 3 had secondary generalization. Four family members had a single isolated seizure; only 1 of the 4 also had migraine with aura. Median age at the onset of aura was 42 years (range 30 to 65). Seizures and migraine attacks were temporally independent in all patients except one. There was no history of febrile seizures. EEG and brain MRI were normal except in 2 patients with age-related white matter changes. Disease penetrance was about 75%.

Teive et al. (2008) commented that the possible relationship between epilepsy and migraine in the family reported by Deprez et al. (2007) was consistent with the hypothesis of cortical spreading depression in epilepsy and migraine put forth by Leao (1944).

Mapping

By genomewide linkage and haplotype analysis of an affected Belgian family, Deprez et al. (2007) identified a 9.95-cM candidate region on chromosome 9q21-q22 between markers GATA152H04 and D9S253 (maximum 2-point lod score of 3.3 at D9S257). The disease haplotype was present in all those with epilepsy and in all those with migraine with aura. The findings suggested a causal monogenic link between epilepsy and migraine with aura in this family.