KCNQ2 developmental and epileptic encephalopathy
KCNQ2 developmental and epileptic encephalopathy is a rare genetic disorder that typically presents with tonic seizures from the first week of life. The seizures can be frequent and often difficult to treat. Seizures can resolve within months or years but can impair the development of several domains such as motor, social, cognitive and language.
Causes
Pathogenic variations in KCNQ2 are associated with developmental and epileptic encephalopathy. KCNQ2 is a voltage gated potassium channel within the brain, located on the long arm of chromosome 20, at position 13.3. KCNQ2 gene is a critical molecular component of the M-current, a subthreshold voltage-gated potassium current controlling neuronal excitability by dampening repetitive action potential firing. DEE is caused by loss of function mutations in the KCNQ2 gene thereby reducing the activation threshold of the neuron and increasing the risk of hyperexcitability. KCNQ2 belongs to a family of ion channels, abbreviated Kv7.2. The KCNQ gene subfamily consists of five members, all encoding voltage-gated potassium channel subunits. The Kv7.1 subunit is expressed in the heart and Kv7.2-5 subunits are most abundantly expressed in the nervous system.Pathophysiology
KCNQ2 channels are voltage-dependent K+ currents that represent the molecular basis of the M-current.KCNQ2 encephalopathy is caused by heterozygous missense or in-frame indel mutations shown to have a dominant negative, or gain of function effect when co-expressed with wild-type subunits.