: Purpose: We studied a large Dutch-Canadian family, in which two very rare hereditary paroxysmal neurologic disorders, familial hemiplegic migraine (FHM) and a “benign familial infantile epileptic syndrome” concur and partially cosegregate. FHM is a dominantly inherited subtype of migraine with attacks of hemiparesis, linked to chromosome 19p13 in 50% of the families tested. Recently mutations in a brain-specific P/Q-type Ca2+ channel α1 subunit gene (CACNLlA4) were identified in families with chromosome 19-linked FHM. The infantile epileptic syndrome resembles to two other dominantly inherited benign epilepsies occurring in the first year of life, benign familial neonatal convulsions (BFNC), assigned to chromosomes 20q13.2 and 8q, and benign infantile familial convulsions (BIFC), as yet unlinked.
Methods: Linkage analysis was performed for the known locations of FHM and BFNC. The question whether the two conditions in this family can be caused by a single gene defect was addressed by additional linkage analysis.
Results: We excluded linkage of the infantile convulsions to markers on chromosome 20q13.2, Sq, or 19p13. This indicates the existence of a third locus for benign familial convulsions in the first year of life. Linkage of FHM to these markers was not formally excluded but seems very unlikely. Statistical analysis of whether, in this family, both conditions are caused by a single gene defect was inconclusive.
Conclusions: We describe a “benign familial infantile epileptic syndrome“ with attacks of FHM at a later age. Further genetic studies in this family may help to unravel the genetic basis of epilepsy or migraine or both.