Objective: Hemiplegic migraine (HM) is a rare subtype of migraine with aura that occurs as a familial or sporadic condition. The 3 culprit genes identified so far do not account for all familial forms of HM. PRRT2 mutations have recently been shown to cause various childhood-onset episodic syndromes including paroxysmal kinesigenic dyskinesia, infantile convulsions with choreoathetosis syndrome, and benign familial infantile epilepsy. Our objective was to test the possible implication of PRRT2 in HM, another episodic disorder with early onset in most cases.
Methods: The whole genomic coding region of PRRT2 was sequenced in 101 index cases with HM that started before age 20 years and for whom no mutation was found in the 3 known HM genes. Affected relatives of mutated patients were analyzed when available.
Results: PRRT2 mutations were identified in 4 patients: the previously reported c.649dupC mutation was found in 2 cases, and a novel mutation, c.649delC, was found in the other 2. One patient with mutation subsequently developed paroxysmal dyskinesia, as well as generalized epileptic seizures.
Conclusions: PRRT2 mutations can occasionally cause HM. This underscores the complexity of the phenotypic consequences of PRRT2 mutations.