KCNT1 gene

KCNT1 gene

The KCNT1 gene encodes a potassium channel that regulates neuronal activity, and gain-of-function mutations in this gene are associated with several severe forms of epilepsy.

Normal Function

The KCNT1 gene provides instructions for making potassium channels that transport potassium ions out of nerve cells (neurons). This ion flow generates currents that activate neurons and facilitate signaling in the brain. The activity of these channels can be increased by a molecule called PKC, which attaches to the channel to strengthen the electrical current.

Health Conditions Related to Genetic Changes

Pathogenic variants in the KCNT1 gene are typically gain-of-function variants, meaning they cause the potassium channel to function excessively, increasing the flow of ions. This enhanced activity leads to neuronal over-excitation and seizures.

Autosomal dominant sleep-related hypermotor epilepsy

Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is characterized by seizures that occur during sleep. These seizures often involve abnormal muscle movements, stiffness, or body positioning. Individuals with KCNT1-related ADSHE often experience early-onset seizures that are resistant to treatment, and may also have intellectual disabilities or psychiatric issues.

Epilepsy of infancy with migrating focal seizures

Epilepsy of infancy with migrating focal seizures (EIMFS) is a severe condition where recurrent seizures begin before the age of 6 months. KCNT1 variants are the most common genetic cause of this condition, which is typically associated with significant developmental delays.

Developmental and epileptic encephalopathy

KCNT1 variants are also associated with developmental and epileptic encephalopathy (DEE). This group of disorders involves:

• Developmental delays and worsening brain function (encephalopathy).
• Seizures that are difficult to control with medication.
• Poor muscle tone (hypotonia).
• Movement disorders and small head size (microcephaly).