Autosomal Dominance of Febrile Seizures?

ABSTRACT & COMMENTARY
Source: Maher J, McLachlan R. Febrile convulsions in selected large families: A single-major-locus of inheritance? Dev Med Child Neurol 1997;39:79-84.

Twin and family studies have suggested genetic influences on febrile seizures. Polygenic, autosomal dominant, and autosomal recessive modes of inheritance have all been suggested. By studying large, multi-generational families, Maher and McLachlan now find evidence of autosomal dominant inheritance of febrile convulsions.

From the epilepsy population at University Hospital, London, Ontario, eight probands with: 1) febrile convulsions as children; 2) three other family members with a history of febrile convulsions; and 3) subsequent recurrent afebrile seizures were identified. Three of their families were studied over five generations, and five of their families were studied over four generations. In total, 333 patients and family members were studied.

Seventy-five of 333 family members had febrile seizures (23%). Sixty of these had only febrile seizures. Fifteen of these later developed afebrile seizures (including 9 who developed temporal lobe epilepsy). Furthermore, 13 other family members developed afebrile seizures with no history of febrile seizures; 12 of these 13 had generalized epilepsy.

In addition to the general review of the structure of these eight pedigrees, several specific details suggested autosomal dominant inheritance of febrile seizures: 1) there was more than one affected generation in each family; 2) male-to-male transmission occurred; 3) three of seven (43%) of the children of the probands had febrile seizures; 4) 50% (17/34) of the probands’ siblings had febrile seizures; and 5) 38% (6/16) of the probands’ parents had febrile convulsions.

COMMENTARY

Maher and McLachlan studied a highly selected population in which their data suggest an autosomal dominant inheritance for febrile seizures. A critical inclusion criterion of their study was for each proband’s family to contain four members affected with febrile seizures allowing the identification of genetic transmission in an autosomal dominant manner. However, one cannot conclude that all febrile seizures arise in this fashion since sporadic cases would not have met Maher and McLachlan’s inclusion criteria.

Interestingly, these "autosomal dominant" febrile seizures were associated with the later development of temporal lobe epilepsy (TLE), a condition not generally regarded as a "genetic" epilepsy syndrome. Perhaps febrile seizures injure medial temporal structures and cause the later development of TLE. On the other hand, Ottman et al (Nature Genet 1995;10:56-60) have described a syndrome of TLE with attacks of auditory hallucinosis, apparently linked to chromosome 10q. Perhaps genetic factors play a greater role in predisposing to TLE than was previously recognized. —drl