Linkage of benign familial infantile convulsions to chromosome 16p12-q12 suggests allelism to the infantile convulsions and choreoathetosis syndrome

The syndrome of benign familial infantile convulsions (BFIC) is an autosoma l dominant epileptic disorder that is characterized by convulsions, with on set at age 3-12 mo and a favorable outcome. BFIC had been linked to chromos ome 19q, whereas the infantile convulsions and choreoathetosis (ICCA) syndr ome, in which BFIC is associated with paroxysmal dyskinesias, had been link ed to chromosome 16p12-q12. BFIC appears to be frequently associated with p aroxysmal dyskinesias, because many additional families from diverse ethnic backgrounds have similar syndromes that have been linked to the chromosome 16 ICCA region. Moreover, one large pedigree with paroxysmal kinesigenic d yskinesias only, has also been linked to the same genomic area. This raised the possibility that families with pure BFIC may be linked to chromosome 1 6 as well. We identified and studied seven families with BFIC inherited as an autosomal dominant trait. Genotyping was performed with markers at chrom osome 19q and 16p12-q12. Although chromosome 19q could be excluded, evidenc e for linkage in the ICCA region was found, with a maximum two-point LOD sc ore of 3.32 for markers D16S3131 and SPN. This result proves that human chr omosome 16p12-q12 is a major genetic locus underlying both BFIC and paroxys mal dyskinesias. The unusual phenotype displayed by one homozygous patient suggests that variability of the ICCA syndrome could be sustained by geneti c modifiers.