Two Novel <i>KCNQ2</i> Mutations in 2 Families With Benign Familial Neonatal Convulsions

Abstract

Benign familial neonatal convulsion is a rare autosomal dominant inherited epilepsy syndrome characterized by unprovoked seizures in the first few days of life, normal psychomotor development, and a positive intergenerational family history of neonatal seizures. Over 90% of the affected individuals have inherited causal mutations in <i>KCNQ2</i>, which encodes for the potassium voltage-gated channel subfamily Q, member 2. Mutations in <i>KCNQ2</i> are also associated with a severe neonatal encephalopathy phenotype associated with poor seizure control and neurodevelopmental deficits. The authors report the clinical presentations, response to medication, and intrafamilial phenotypic variability in 2 families with benign familial neonatal convulsions, carrying previously unreported heterozygous missense mutations, c.1066C>G (p.Leu356Val) and c.1721G<b><</b>A (p.Gly574Asp), in <i>KCNQ2</i>. The cases reported herein suggest that inherited missense mutations in <i>KCNQ2</i> can be associated with an intermediate phenotype and illustrate the challenges associated with prognosis and counselling for individuals with inherited missense mutations in <i>KCNQ2</i>.