KCNQ3-related disorders are caused by a change in the genetic material (pathogenic variants) in the KCNQ3 gene located on chromosome 8. KCNQ3 encodes for voltage gated potassium channel subunits which are widely expressed in the nervous system. These subunits form channels with specific functional properties known as the M-current. This current suppresses repetitive transmission of electrical signals (neuronal firing). In this way, it has a critical role in controlling neuronal excitability.
Disease-causing variants in KCNQ3 cause the potassium channel to be closed more than it should be (loss-of-function) and have been associated with a broad spectrum of neonatal or infantile-onset epilepsy with or without developmental delay. KCNQ2 variants that open the potassium channel more than it should be (gain-of-function) are mainly characterized by developmental delay and autistic features without neonatal seizures.
Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother.
Disease causing variants are most often inherited by an autosomal dominant mode. This means that one of the two KCNQ3 copies with a variant is enough to cause the disease. Mildly affected patients associated with self-limiting neonatal/infantile seizures without developmental delay often inherited the variant from a parent. In contrast, almost all severely affected individuals with developmental delay have a new, spontaneous mutation that is not inherited (de novo), or they carry a disease-causing variant in each copy of the gene (autosomal recessive mode of inheritance).
KCNQ3