• Nadine Pelzer, Joost Haan, Anine H Stam, Lisanne S Vijfhuizen, Stephany C Koelewijn, Amber Smagge, Boukje de Vries, Michel D Ferrari, van den MaagdenbergArn M J MAMJMFrom the Departments of Neurology (N.P., J.H., A.H.S., A.S., M.D.F., A.M.J.M.v.d.M., G.M.T.) and Human Genetics (L.S.V., S.C.K., B.d.V., A.M.J.M.v.d.M.), Leiden University Medical Centre; and Department of Neurology (J.H.),, and Gisela M Terwindt.
• From the Departments of Neurology (N.P., J.H., A.H.S., A.S., M.D.F., A.M.J.M.v.d.M., G.M.T.) and Human Genetics (L.S.V., S.C.K., B.d.V., A.M.J.M.v.d.M.), Leiden University Medical Centre; and Department of Neurology (J.H.), Alrijne Hospital, Leiderdorp, the Netherlands.
• Neurology. 2018 Feb 13; 90 (7): e575-e582.

ObjectiveTo investigate whether the clinical characteristics of patients with hemiplegic migraine with and without autosomal dominant mutations in CACNA1A, ATP1A2, or SCN1A differ, and whether the disease may be caused by mutations in other genes.MethodsWe compared the clinical characteristics of 208 patients with familial (n = 199) or sporadic (n = 9) hemiplegic migraine due to a mutation in CACNA1A, ATP1A2, or SCN1A with those of 73 patients with familial (n = 49) or sporadic (n = 24) hemiplegic migraine without a mutation in these genes. In addition, 47 patients (familial: n = 33; sporadic: n = 14) without mutations in CACNA1A, ATP1A2, or SCN1A were scanned for mutations in novel genes using whole exome sequencing.ResultsPatients with mutations in CACNA1A, ATP1A2, or SCN1A had a lower age at disease onset, larger numbers of affected family members, and more often attacks (1) triggered by mild head trauma, (2) with extensive motor weakness, and (3) with brainstem features, confusion, and brain edema. Mental retardation and progressive ataxia were exclusively found in patients with a mutation. Whole exome sequencing failed to identify pathogenic mutations in new genes.ConclusionsMost patients with hemiplegic migraine without a mutation in CACNA1A, ATP1A2, or SCN1A display a mild phenotype that is more akin to that of common (nonhemiplegic) migraine. A major fourth autosomal dominant gene for hemiplegic migraine remains to be identified. Our observations might guide physicians in selecting patients for mutation screening and in providing adequate genetic counseling.© 2018 American Academy of Neurology.

21 keywords...

hide…