Familial Hemiplegic Migraine

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Familial hemiplegic migraine is an autosomal-dominant subtype of migraine with aura with strong penetrance. Approximately 55% of affected families can be linked to chromosome 19,15% on chromosome 1, and 30% are still to be determined. Joutel et al. found that familial hemiplegic migraine was linked to chromosome 19 in two large French pedigrees. The critical area was mapped to a 30-cm region of the short arm of chromosome 19p13.1. Familial hemiplegic migraine is due to missense mutation in a pore-forming human a1A subunit of neuronal P/Q-type Ca2 + channels (CACNA1A). More than 15 missense mutations in the CACNA1A have been reported. P/Q calcium channels are coupled to neurotransmitter release and expressed on soma and dendrites throughout the mammalian brain. How these mutations affect the functioning of the calcium channel is not well understood. Recent reports show calcium currents attributed to a1A channel mutations partially diminished, and, in some studies, increased in other mutations. Tottering mice have a similar genetic defect in the a1A calcium channel. These mice have resistance to the induction of cortical spreading depression. Familial hemiplegic migraine has been linked to two other gene loci on chromosome 1q21-23 and chromosome 1q31, respectively. Patients with the chromosome 19 mutation may also have cerebellar signs and essential tremor, and those with chromosome 1 mutations have associated epilepsy and febrile convulsions.

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