[HTML][HTML] The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel

A Ducros, C Denier, A Joutel, M Cecillon… - … England Journal of …, 2001 - Mass Medical Soc
A Ducros, C Denier, A Joutel, M Cecillon, C Lescoat, K Vahedi, F Darcel, E Vicaut
New England Journal of Medicine, 2001Mass Medical Soc
Background Familial hemiplegic migraine, an autosomal dominant disorder characterized
by attacks of transient hemiparesis followed by a migraine headache, is divided into pure
familial hemiplegic migraine (affecting 80 percent of families) and familial hemiplegic
migraine with permanent cerebellar signs (affecting 20 percent of families). Mutations in
CACNA1A, which encodes a neuronal calcium channel, are present in 50 percent of families
with hemiplegic migraine, including all those with cerebellar signs. We studied the various …
Background
Familial hemiplegic migraine, an autosomal dominant disorder characterized by attacks of transient hemiparesis followed by a migraine headache, is divided into pure familial hemiplegic migraine (affecting 80 percent of families) and familial hemiplegic migraine with permanent cerebellar signs (affecting 20 percent of families). Mutations in CACNA1A, which encodes a neuronal calcium channel, are present in 50 percent of families with hemiplegic migraine, including all those with cerebellar signs. We studied the various clinical manifestations associated with mutations in CACNA1A in 28 families with hemiplegic migraine with and without cerebellar signs.
Methods CACNA1A
was analyzed and nine mutations were detected in 15 of 16 probands of families affected by hemiplegic migraine and cerebellar signs, in 2 of 3 subjects with sporadic hemiplegic migraine and cerebellar signs, and in 4 of 12 probands of families affected by pure hemiplegic migraine. Genotyping of probands and relatives identified a total of 117 subjects with mutations whose clinical manifestations were assessed in detail.
Results
Eighty-nine percent of the subjects with mutations had attacks of hemiplegic migraine. One third had severe attacks with coma, prolonged hemiplegia, or both, with full recovery. All nine mutations, including five newly identified ones, were missense mutations. Six mutations were associated with hemiplegic migraine and cerebellar signs, and 83 percent of the subjects with these six mutations had nystagmus, ataxia, or both. Three mutations were associated with pure hemiplegic migraine.
Conclusions
Hemiplegic migraine in subjects with mutations in CACNA1A has a broad clinical spectrum. This clinical variability is partially associated with the various types of mutations.
The New England Journal Of Medicine