Repetitive Daily Blindness with Hemiplegic Migraine and SCN1A Mutations

Two novel SCN1A mutations are identified in two unrelated families with familial hemiplegic migraine and a unique phenotype of elicited repetitive daily blindness, in a report from Hopital Lariboisiere, and other centers in Paris, France, and Geneva, Switzerland. The proband of family 1 is an 18-year-old woman with recurrent attacks of hemiplegic migraine since age 6, and repeated, daily (up to 10 times per day), stereotyped bilateral transient blindness of maximum 10 sec duration. During the attack, pupils are dilated with absent direct and indirect pupillary reflexes. Visual symptoms are spontaneous or triggered by rubbing the eyes. Blindness occurs without associated headache or other neurologic symptoms, and independently of attacks of hemiplegic migraine that occur irregularly from a maximum of 2 per week to one every 2 years. The neurologic, visual acuity, electroretinogram, and fundus examinations are normal outside the attacks. Brain MRI shows a hypersignal T2-WI lesion in the territory of the right inferior cerebellar artery and a few ischemic sequelae in the left posterior inferior cerebellar artery territory. Parenchymal cerebellar lesions were also present on CT at 6 years of age. The proband’s mother, sister, and maternal grandfather had hemiplegic migraine without episodic blindness. Family 2 with the association of episodic blindness and hemiplegic migraine in 4 out of 5 affected members was reported previously. The transient daily blindness is suggestive of a retinal spreading depression, triggered by rubbing the eyes. [1]

COMMENT. Familial hemiplegic migraine, a genetically heterogeneous disorder, is linked to three genes, including SCN1A. The unique eye phenotype of elicited repetitive daily blindness cosegregating with familial hemiplegic migraine is previously reported in a single Swiss family. The present report identifies SCN1A mutations in both the Swiss and French families with this unique phenotype, and excludes mutation in CACNA1A and ATP1A2, genes most frequently involved in familial hemiplegic migraine. SCN1A is also involved in febrile seizures, GEFS+ and Dravet syndrome.