Abstracts

Rationale: Benign familial neonatal seizures (BFNS) is an autosomal dominant epilepsy syndrome characterized by afebrile seizures starting in the first weeks of life. Seizures remit spontaneously after a few weeks or months and patients usually have a normal intellectual outcome. Mutations in KCNQ2 and KCNQ3, encoding the voltage-gated potassium channel subunits Kv7.2 and Kv7.3, have been identified in the majority of BFNS families. To date, approximately 70 different KCNQ2 mutations have been described including missense, frameshift, nonsense, and splice-site mutations. Electrophysiological studies revealed that several of these mutations cause a loss of function, suggesting that haploinsufficiency of KCNQ2 leads to BFNS.Methods: We selected 21 patients with a benign form of epilepsy starting in the first year of life. We excluded mutations in KCNQ2 and KCNQ3 in all patients using direct sequencing. We studied these patients for microdeletions affecting the KCNQ2 gene using Multiplex Ligation-dependent Probe Amplification (MLPA).Results: We observed a microdeletion affecting KCNQ2 in 2 patients. In the first patient the deletion encompassed the entire KCNQ2 gene. The second patient had a deletion of only exon 6 and 7.Conclusions: These findings demonstrate that analysis for microdeletions involving KCNQ2 in BFNS patients lacking point mutations in KCNQ2 can be used in diagnostic settings.