GENETIC-ANALYSIS OF KIFAFA, A COMPLEX FAMILIAL SEIZURE DISORDER

Kifafa is the Swahili name for an epileptic seizure disorder, first re ported in the early 196Os, that is prevalent in the Wapogoro tribe of the Mahenge region of Tanzania in eastern Africa. A 1990 epidemiologic al survey of seizure disorders in this region reported a prevalence in the range of 19/1,000-36/1,000, with a mean age at onset of 11.6 year s; 80% of those affected had onset prior to 20 years of age. A team of investigators returned to Tanzania in 1992 and collected data on >1,6 00 relatives of 26 probands in 20 kifafa families. We have undertaken a genetic analysis of these data in order to detect the presence of fa milial clustering and whether such aggregation could be attributed to genetic factors. Of the 127 affected individuals in these pedigrees, 2 3 are first-degree relatives (parent, full sibling, or offspring) of t he 26 probands; 20 are second-degree relatives (half-sibling, grandpar ent, uncle, or aunt). When corrected for age, the risk to first-degree relatives is .15; the risk to second-degree relatives is .063. These risks are significantly higher than would be expected if there were no familial clustering. Segregation analysis, using PAP (rev.4.0), was u ndertaken to clarify the mode of inheritance. Among the Mendelian sing le-locus models, an additive model was favored over either a dominant, recessive, or codominant model. The single-locus model could be rejec ted when compared with the mixed Mendelian model (inclusion of a polyg enic background), although the major-gene component tends to be recess ive. However, the hypothesis of Mendelian transmission could be reject ed, suggesting that, although kifafa does aggregate in these families, the mode of inheritance is genetically complex.