PRRT2 mutations in familial infantile seizures, paroxysmal dyskinesia, and hemiplegic migraine

Objective: To perform a clinical and genetic study of a family with benign familial infantile seizures\r\n(BFIS) and, upon finding a PRRT2 gene mutation, to study a cohort of probands with a similar\r\nphenotype. We extended the study to all available family members to find out whether PRRT2\r\nmutations cosegregated with additional symptoms.\r\nMethods: We carried out a clinical and genealogic study of a 3-generation family and of 32 additional\r\nprobands with BFIS (11 families), infantile convulsions and paroxysmal choreoathetosis (ICCA) (9 families),\r\nBFIS/generalized epilepsy with febrile seizures plus (5 families), and sporadic benign neonatal or\r\ninfantile seizures (7 probands/families). We performed a genetic study consisting of linkage analysis\r\nand PRRT2 screening of the 33 probands/families.\r\nResults: We obtained a positive linkage in the 16p11.3-q23.1 chromosomal region in the large BFIS\r\nfamily. Mutation analysis of PRRT2 gene revealed a c.649dupC (p.Arg217Profs*8) in all affected\r\nindividuals. PRRT2 analysis of the 32 additional probands showed mutations in 10, 8 familial and 2\r\nsporadic, probands. Overall we found PRRT2 mutations in 11 probands with a mutation rate of 11\r\nout of 33 (33%). BFIS co-occurred with migraine and febrile seizures in 2 families, with childhood\r\nabsence epilepsy in one family and with hemiplegic migraine in one family.\r\nConclusion: Our results confirm the predominant role of PRRT2 mutations in BFIS and expand the\r\nspectrum of PRRT2-associated phenotypes to include febrile seizures, childhood absence seizures,\r\nmigraine, and hemiplegic migraine. Neurology  2012;79:2109–2114