Genetic studies of febrile convulsions: analysis of twin and family data

Abstract

Children with febrile convulsions (FC) including 46 twin pairs, 1913 families including 393 sibling pairs, and 42 three-generation FC kindreds have been studied. Twin studies: (1) The pairwise concordance rate for FC was 69% (18/26 pairs) in monozygotic (MZ) and 20% (4/20 pairs) in dizygotic (DZ) twins (P less than 0.01). (2) The intra-pair similarity of clinical symptoms in 18 concordant MZ twin pairs showed a positive significant correlation, particularly in 4 items--duration of seizure, exogenous factors, intelligence level, and background EEG abnormality. These correlations were greater than those in sibling pairs. (3) No evident cause for discordance was detected in 8 discordant MZ twin pairs, and many dissimilar symptoms were observed in 4 concordant DZ twin pairs. Sibship studies: A large positive correlation of some clinical symptoms was observed in sibling pairs concordant for FC: age at onset of FC, degree of fever, duration of seizure, exogenous factors, and background EEG abnormality (r = +0.2- +0.6). Family history analysis: Morbidity risk among near relatives (17% in parents, 23% in siblings) than in second- (6.1%) or third-degree relatives (4.6%). The difference was found between: sibling greater than parents, uncles greater than aunts, male cousins greater than female cousins. Segregation analysis showed maternal preponderance. In 42 three-generation kindreds the morbidity risk was higher in siblings (32%), uncles/aunts (14%), and cousins (6.4%) than in relatives of other probands. Characteristic findings in FC patients with family history: Characteristic findings in FC patients with an FC parent or sibling, compared with those with no family history, were early onset of FC, lower degree of fever, longer duration of seizure, many recurrences, FC recurrence after age 3, and background EEG abnormality. Similar findings were more markedly observed in 42 3-generation kindreds. Mode of inheritance: A multifactorial mode of inheritance for FC receives some support from this study, and the heritability was estimated as 75%.