2.1. Malignant Migrating Partial Seizures of Infancy

At least six KCNT1 gene mutations have been found in individuals with malignant migrating partial seizures of infancy (MMPSI). This condition is characterized by recurrent seizures beginning before the age of 6 months as well as profound developmental delay. In MMPSI, seizure activity in the brain can spread (migrate) from one region to another during an episode.

The KCNT1 gene mutations involved in MMPSI change single protein building blocks (amino acids) in the KCNT1 protein. The electrical currents generated by potassium channels made with the altered KCNT1 protein are abnormally increased, as though the channels were turned on by PKC. The increased electrical currents allow unregulated excitation of neurons in the brain. When neurons are abnormally excited, seizures develop. Repeated seizures contribute to the developmental delay that is characteristic of this condition.

2.2. Other Disorders

Mutations in the KCNT1 gene have been found in several people with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), which causes seizures that usually occur at night (nocturnally) while an affected person is sleeping. In addition to seizures, most affected individuals with KCNT1 gene mutations have psychiatric problems, such as aggression, episodes of unresponsiveness (catatonia), or a distorted view of reality (psychosis), and about half have intellectual disability. The KCNT1 gene mutations involved in this condition change single amino acids in the KCNT1 protein; however, it is unclear what effects these changes have on the function of potassium channels or how they lead to the features of ADNFLE.