Hemiplegic Migraine Associated With <i>PRRT2</i> Variations
Florence Riant, Caroline Roos, Agathe Roubertie, Cécile Barbance, Jessica Hadjadj, Stéphane Auvin, Guillaume Baille, Marion Beltramone, Cécile Boulanger, Alice Cahn, Florina Cata, Emmanuel Cheuret, J. Cuvellier, Antoine Defo, Geneviève Demarquay, Anne Donnet, Nicolas Gaillard, Evelyne Massardier, Nathalie Guy, Sylvie Lamoureux, L. Le Moigno, Christian Lucas, Diana Ratiu, Sylvain Redon, Caroline Rey, Christel Thauvin, François Viallet, Elisabeth Tournier‐Lasserve, Anne Ducros
Abstract
<h3>Background and Objective</h3> <i>PRRT2</i> variants have been reported in a few cases of patients with hemiplegic migraine. To clarify the role of <i>PRRT2</i> in familial hemiplegic migraine, we studied this gene in a large cohort of affected probands. <h3>Methods</h3> <i>PRRT2</i> was analyzed in 860 probands with hemiplegic migraine, and <i>PRRT2</i> variations were identified in 30 probands. Genotyping of relatives identified a total of 49 persons with variations whose clinical manifestations were detailed. <h3>Results</h3> <i>PRRT2</i> variations were found in 12 of 163 probands who previously tested negative for <i>CACNA1A</i>, <i>ATP1A2</i>, and <i>SCN1A</i> variations and in 18 of 697 consecutive probands screened simultaneously on the 4 genes. In this second group, pathogenic variants were found in 105 individuals, mostly in <i>ATP1A2</i> (42%), followed by <i>CACNA1A</i> (26%), <i>PRRT2 (</i>17%), and <i>SCN1A</i> (15%). The <i>PRRT2</i> variations included 7 distinct variants, 5 of which have already been described in persons with paroxysmal kinesigenic dyskinesia and 2 new variants. Eight probands had a deletion of the whole <i>PRRT2</i> gene. Among the 49 patients with variations in <i>PRRT2</i>, 26 had pure hemiplegic migraine and 16 had hemiplegic migraine associated with another manifestation: epilepsy (8), learning disabilities (5), hypersomnia (4), or abnormal movement (3). Three patients had epilepsy without migraine: 2 had paroxysmal kinesigenic dyskinesia without migraine, and 1 was asymptomatic. <h3>Discussion</h3> <i>PRRT2</i> should be regarded as the fourth autosomal dominant gene for hemiplegic migraine and screened in any affected patient, together with the 3 other main genes. Further studies are needed to understand how the same loss-of-function <i>PRRT2</i> variations can lead to a wide range of neurologic phenotypes, including paroxysmal movement disorder, epilepsy, learning disabilities, sleep disorder, and hemiplegic migraine.