Phenotypic expression of benign familial neonatal convulsions linked to chromosome 20

To determine whether the syndrome of benign familial neonatal convulsions in a large family was linked to markers on chromosome 20q and to study the seizure patterns in affected individuals.

A clinical and molecular biologic study of a single large family in which the probands were identical twins with benign familial neonatal convulsions.

Thirteen living affected family members and 27 living unaffected family members were evaluated.

Multipoint linkage analysis with use of the chromosome 20q markers CMM6 and RMR6 gave a maximum lod score of 3.13 at theta = 0.063, indicating linkage in this family. Of the 13 affected members, 10 had known neonatal seizures. Four subjects had febrile seizures, of whom only two had known neonatal seizures. Two members had afebrile seizures later, one of whom had not previously suffered neonatal or febrile seizures.

The phenotypic heterogeneity in this family, with an epilepsy syndrome determined by a single gene, was striking. This suggests that molecular genetic approaches to the common forms of idiopathic epilepsy, involving patients with clinically similar phenotypes from unrelated families, may be inappropriate.