Partial cosegregation of familial hemiplegic migraine and a benign familial infantile epileptic syndrome.
OBJECTIVE
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 alpha1 subunit gene (CACNL1A4) 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, 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 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.
Terwindt
G M
GM
Department of Neurology, Leiden University Medical Center, The Netherlands.
Ophoff
R A
RA
Lindhout
D
D
Haan
J
J
Halley
D J
DJ
Sandkuijl
L A
LA
Brouwer
O F
OF
Frants
R R
RR
Ferrari
M D
MD
D017668:Age of Onset; D000368:Aged; D015220:Calcium Channels / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics*; D005190:Family; D008040:Genetic Linkage; D005819:Genetic Markers; D006429:Hemiplegia / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008881:Migraine Disorders / Q000175:diagnosis / Q000235:genetics*; D008957:Models, Genetic; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012640:Seizures / Q000175:diagnosis / Q000235:genetics
D015220:Calcium Channels; D005819:Genetic Markers