The genetic basis of juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy is diagnosed in around 5–10% of all cases of epilepsy and 18% of all cases with genetic generalised epilepsies. 1 Janz D Durner M Juvenile myoclonic epilepsy. in: Engel Jr, J Pedley TA Epilepsy: a comprehensive textbook. Lippincott-Raven, Philadelphia1997: 2389-2400 Google Scholar , 2 Syvertsen M Hellum MK Hansen G et al. Prevalence of juvenile myoclonic epilepsy in people <30 years of age-A population-based study in Norway. Epilepsia. 2017; 58: 105-112 Crossref PubMed Scopus (19) Google Scholar This disease typically presents in adolescence, with myoclonic jerks at awakening and tonic-clonic seizures in nearly 80% of patients. 3 Striano P Belcastro V Update on pharmacotherapy of myoclonic seizures. Expert Opin Pharmacother. 2017; 18: 187-193 Crossref PubMed Scopus (11) Google Scholar In untreated patients, EEG shows diffuse 3–6 Hz spike or polyspikes, and focal abnormalities or photoparoxysmal responses are found in up to 70% of individuals. Juvenile myoclonic epilepsy is usually treatable with anti-epileptic drugs, although about 15% of patients are drug-resistant. 3 Striano P Belcastro V Update on pharmacotherapy of myoclonic seizures. Expert Opin Pharmacother. 2017; 18: 187-193 Crossref PubMed Scopus (11) Google Scholar The genetic component of the disease is complex and heterogeneous; 22 chromosomal loci and seven genes have been associated with the disease, six of which encode for ion channels subunits. 4 Santos BPD Marinho CRM Marques TEBS et al. genetic susceptibility in juvenile myoclonic epilepsy: systematic review of genetic association studies. PLoS One. 2017; 12: e017962 Crossref Scopus (22) Google Scholar However, most families with juvenile myoclonic epilepsy studied so far have mutations in EFHC1, 5 Suzuki T Delgado-Escueta AV Aguan K et al. Mutations in EFHC1 cause juvenile myoclonic epilepsy. Nat Genet. 2004; 36: 842-849 Crossref PubMed Scopus (284) Google Scholar , 6 Annesi F Gambardella A Michelucci R et al. Mutational analysis of EFHC1 gene in Italian families with juvenile myoclonic epilepsy. Epilepsia. 2007; 48: 1686-1690 Crossref PubMed Scopus (40) Google Scholar which encodes a microtubule-associated protein that is involved in cell division and corticogenesis during brain development. 7 de Nijs L Wolkoff N Coumans B Delgado-Escueta AV Grisar T Lakaye B Mutations of EFHC1, linked to juvenile myoclonic epilepsy, disrupt radial and tangential migrations during brain development. Hum Mol Genet. 2012; 21: 5106-5117 Crossref PubMed Scopus (25) Google Scholar