KCNA1 gene

At least 20 mutations in the KCNA1 gene have been identified in people with episodic ataxia type 1 (EA1). People with this form of the condition have brief, recurrent episodes of poor coordination and balance (ataxia). Between episodes, many affected individuals experience myokymia, a muscle abnormality that can cause involuntary muscle cramping, stiffness, and continuous, fine muscle twitching that appears as rippling under the skin.

Most of the KCNA1 mutations responsible for episodic ataxia change single protein building blocks (amino acids) in the alpha subunit of the Kv1.1 channel. Some of these changes prevent the assembly of functional channels, while other mutations alter the channel's structure. When Kv1.1 channels are missing or abnormal, the flow of potassium ions into neurons is reduced. This decrease in potassium ions overexcites certain neurons in the brain, which disrupts normal communication between these cells. Although changes in signaling between neurons underlie the episodes of uncoordinated movement seen in people with episodic ataxia, it is unclear how altered potassium ion transport causes the specific features of the condition.

Mutations in the KCNA1 gene have been found to cause a range of signs and symptoms affecting the nervous system. In at least one family, isolated myokymia (continuous muscle twitching and spasms without episodes of ataxia) has been attributed to KCNA1 mutations. Changes in this gene have also been identified in a small number of people with epilepsy. Like the KCNA1 mutations that underlie episodic ataxia, the mutations that cause isolated myokymia and epilepsy reduce the flow of potassium ions through Kv1.1 channels, disrupting normal communication between neurons in the brain. Researchers are working to determine why mutations in this single gene can cause several different disorders of the nervous system.