CHRNA4 variant causes paroxysmal kinesigenic dyskinesia and genetic epilepsy with febrile seizures plus?

Paroxysmal kinesigenic dyskinesia (PKD) and epilepsy are thought to have a shared genetic etiology. PRRT2 has been identified as a causative gene of both disorders. In this study, we aim to explore the potential novel causative gene in a PRRT2-negative family with three individuals diagnosed with PKD or genetic epilepsy with febrile seizures plus (GEFS+).

Clinical data were collected from all the affected and unaffected members of a PKD/GEFS+ family. The Brain magnetic resonance imaging and 24 h video-EEG of all three affected members were analyzed. Targeted gene-panel sequencing was used to detect the genetic defect in genomic DNAs of three affected and five normal individuals. Co-segregation analysis of putatively pathogenic mutations with the phenotype was carried out in all the family members alive to examine the inheritance status.

The inheritance model of this pedigree was autosomal dominant. A novel, fully co-segregated mutation (NM_000744: c.979G > A) in CHRNA4 was identified in the family with three individuals diagnosed with PKD or GEFS+.

CHRNA4 may be a novel gene causing of PKD and GEFS+. Our study extends the genotypic-phenotypic spectrum of combined epileptic and dyskinetic syndromes, and provides a genetic linkage between PKD and GEFS+.