Benign familial neonatal convulsions: evidence for clinical and genetic heterogeneity.

The gene for autosomal dominant "benign" familial neonatal convulsions, a transient, primary epilepsy of infancy, has recently been assigned to chromosome 20q. To determine whether this disorder is genetically heterogeneous, we performed linkage analysis in two previously unreported pedigrees with benign familial neonatal convulsions in which clinical heterogeneity was evident. There were 14 affected persons in the first family, and none had seizures (febrile or afebrile) after the age of 2 months. The second family had 13 affected individuals and 2 obligate carriers; seizures frequently did not remit until 6 to 24 months, febrile convulsions occurred in at least 2 patients, apparent audiogenic seizures occurred in 4 patients, and 1 individual had refractory epilepsy until late adolescence. Linkage studies with the chromosome 20 markers D20S19 and D20S20 were performed in both families. The resulting data favored linkage of the disease and marker loci in Family 2 by a maximum odds ratio of 45:1 at 6% recombination. In Family 1, however, the odds were greater than 20,000:1 against linkage at 10% recombination or less. We conclude that the syndrome of benign familial neonatal convulsions is clinically and genetically heterogeneous. Further study will be necessary to clarify the relationship between phenotype and genotype in this disorder.