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 Volume 72, Number 13, March 31, 2009
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NEUROLOGY 2009;72:1178-1183
© 2009 American Academy of Neurology

Elicited repetitive daily blindness

A new phenotype associated with hemiplegic migraine and SCN1A mutations

K. Vahedi, MD, C. Depienne, PhD, D. Le Fort, MD, F. Riant, MD, P. Chaine, MD, O. Trouillard, MS, A. Gaudric, MD, M. A. Morris, DPhil, E. LeGuern, MD, PhD, E. Tournier-Lasserve, MD and M-G Bousser, MD

From AP-HP (K.V., P.C., M.-G.R.), Assistance Publique Hôpitaux de Paris, Hôpital Lariboisière, Service de Neurologie, Paris; AP-HP (K.V., F.R., A.G., E.T.-L., M.-G.R.), Assistance Publique Hôpitaux de Paris, Hôpital Lariboisière, and Centre de Référence pour les Maladies Vasculaires Rares du Système Nerveux Central et de la Rétine, Paris; INSERM UMR_S 679 Neurologie & Thérapeutique Expérimentale (C.D., E.L.), GH Pitié-Salpêtrière, Paris; AP-HP (C.D., O.T., E.L.), Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Département de Génétique, Cytogénétique et Embryologie, Paris; UPMC Univ Paris 06 (C.D., E.L.), UMR_S679, Paris, France; Cabinet de Neurologie (D.L.F.), Geneva, Switzerland; AP-HP (F.R., E.T.-L.), Groupe Hospitalier Lariboisière-Fernand-Widal, Laboratoire de Génétique, Paris; INSERM UMR_S 740 (F.R., E.T.-L., M.-G.R.), Université Paris 7-Denis Diderot, Faculté de Médecine, Site Lariboisière, Paris; AP-HP (A.G.), Assistance Publique Hôpitaux de Paris, Hôpital Lariboisière, Service d'Ophtalmologie, Paris, France; and Service of Genetic Medicine (M.A.M.), University Hospitals, Geneva, Switzerland.

Address correspondence and reprint requests to Dr. Katayoun Vahedi, APHP-Lariboisière Hospital, Department of Neurology, 2 rue Ambroise Paré, 75010 Paris, France katayoun.vahedi{at}lrb.aphp.fr

Objective: Familial hemiplegic migraine (FHM) is a genetically heterogeneous disorder in which three genes, CACNA1A, ATP1A2, and SCN1A, are currently known to be involved. FHM is occasionally associated with other neurologic symptoms such as cerebellar ataxia or epileptic seizures. A unique eye phenotype of elicited repetitive daily blindness (ERDB) has also been reported to be cosegregating with FHM in a single Swiss family.

Methods: We report an additional family in whom the proband had, in addition to FHM, typical ERDB. In this family and the previously reported Swiss family, the whole coding region of the SCN1A gene was screened after exclusion of mutation in CACNA1A and ATP1A2 genes.

Results: We identified two novel SCN1A mutations (c.4495T>C/p.Phe1499Leu and c.4467G>C/p.Gln1489His missense substitutions) in exons 24 and 23, respectively, segregating with the disease in all living affected members. Both mutations were absent from 180 healthy Caucasian controls and were located in an intracellular loop highly conserved throughout evolution.

Conclusion: We report new clinical data supporting cosegregation of familial hemiplegic migraine and the new eye phenotype of elicited repetitive daily blindness and two novel SCN1A mutations as the underlying genetic defect in two unrelated families. SCN1A encodes the voltage-gated sodium channel Nav1.1 that is highly expressed in the CNS including the retina. This remarkably stereotyped new eye phenotype has clinical characteristics of abnormal propagation of the retinal electrical signal that may be a retinal spreading depression. These results suggest that SCN1A mutations, which alter neuronal brain excitability, may occasionally alter retinal cell excitability.

Abbreviations: ERDB = elicited repetitive daily blindness; FHM = familial hemiplegic migraine.

*These authors contributed equally.

Disclosure: The authors report no disclosures.

Received October 1, 2008. Accepted in final form January 20, 2009.






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