PARTIAL COSEGREGATION OF FAMILIAL HEMIPLEGIC MIGRAINE AND A BENIGN FAMILIAL INFANTILE EPILEPTIC SYNDROME

Purpose: We studied a large Dutch-Canadian family, in which two very r are hereditary paroxysmal neurologic disorders, familial hemiplegic mi graine (FHM;HM) and a ''benign familial infantile epileptic syndrome'' concur and partially cosegregate. FHM is a dominantly inherited subty pe 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 alpha 1 subunit gene (CACNL1A4) were identified in families with chromosome 19-linked FHM. The infantile epileptic sy ndrome resembles to two other dominantly inherited benign epilepsies o ccurring in the first year of life, benign familial neonatal convulsio ns (BFNC), assigned to chromosomes 20q13.2 and sq, and benign infantil e familial convulsions (BIFC), as yet unlinked. Methods: Linkage analy sis was performed for the known locations of FHM and BFNC. The questio n 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, 8q, 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 desc ribe a ''benign familial infantile epileptic syndrome'' with attacks o f FHM at a later age. Further genetic studies in this family may help to unravel the genetic basis of epilepsy or migraine or both.