title: Epilepsy in hemiplegic migraine: Genetic mutations and clinical implications.
abstract: Objective We performed a systematic review on the comorbidities of familial/sporadic hemiplegic migraine (F/SHM) with seizure/epilepsy in patients with CACNA1A, ATP1A2 or SCN1A mutations, to identify the genotypes associated and investigate for the presence of mutational hot spots. Methods We performed a search in MEDLINE and in the Human Gene Mutation and Leiden Open Variation Databases for mutations in the CACNA1A, ATP1A2 and SCN1A genes. After having examined the clinical characteristics of the patients, we selected those having HM and seizures, febrile seizures or epilepsy. For each gene, we determined both the frequency and the positions at protein levels of these mutations, as well as the penetrance of epilepsy within families. Results Concerning F/SHM-Epilepsy1 (F/SHME1) and F/SHME2 endophenotypes, we observed a prevalent involvement of the transmembrane domains, and a strong correlation in F/SHME1 when the positively charged amino acids were involved. The penetrance of epilepsy within the families was highest for patients carrying mutation in the CACNA1A gene (60%), and lower in those having SCN1A (33.3%) and ATP1A2 (30.9%) mutations. Conclusion Among the HM cases with seizure/epilepsy, we observed mutational hot spots in the transmembrane domains of CACNA1A and ATP1A2 proteins. These findings could lead to a better understanding of the pathological mechanisms underlying migraine and epilepsy, therein guaranteeing the most appropriate therapeutic approach.
authors.affiliation: 1 Centro di Riferimento Regionale di Genetica Medica, Ospedale S Maria della Misericordia, Perugia, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Prontera
authors.affiliation: 2 Clinica Neurologica, Università degli Studi di Perugia, Dipartimento di Medicina, Ospedale S Maria della Misericordia, Perugia, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Sarchielli
authors.affiliation: 2 Clinica Neurologica, Università degli Studi di Perugia, Dipartimento di Medicina, Ospedale S Maria della Misericordia, Perugia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Caproni
authors.affiliation: 2 Clinica Neurologica, Università degli Studi di Perugia, Dipartimento di Medicina, Ospedale S Maria della Misericordia, Perugia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Bedetti
authors.affiliation: 3 Centro Cefalee, UOC Neurologia, Ospedale S Eugenio, Rome, Italy.
authors.forename: L M
authors.initials: LM
authors.lastname: Cupini
authors.affiliation: 2 Clinica Neurologica, Università degli Studi di Perugia, Dipartimento di Medicina, Ospedale S Maria della Misericordia, Perugia, Italy.|4 IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Calabresi
authors.affiliation: 2 Clinica Neurologica, Università degli Studi di Perugia, Dipartimento di Medicina, Ospedale S Maria della Misericordia, Perugia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Costa
mesh_terms: D004827:Epilepsy / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D020325:Migraine with Aura / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human; D000254:Sodium-Potassium-Exchanging ATPase
keywords: ATP1A2; CACNA1A; FHM; SCN1A; epilepsy; genetics; migraine