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Previous Volume 345:17-24 July 5, 2001 Number 1 Next

	Full Text PDF Editorial by Hoffman, E. P. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

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.

Source Information

From INSERM E99-21, Faculté de Médecine Lariboisière, Paris (A.D., C.D., A.J., M.C., C.L., E.T.-L.); the Département de Neurologie (A.D., K.V., M.-G.B.) and Laboratoire de Génétique (A.J., M.C., E.T.-L.), Hôpital Lariboisière, Paris; the Département de Neurologie, Centre Hospitalier Universitaire, Rennes, France (F.D.); and the Laboratoire de Biophysique, Hôpital Fernand Widal, Paris (E.V.).

Address reprint requests to Dr. Ducros at the Department of Neurology, Hôpital Lariboisière, 2 rue Ambroise Paré, 75475 Paris CEDEX 10, France, or at anne.ducros{at}lrb.ap-hop-paris.fr.

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