KCNA1

Many variants (also called 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 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 variants that cause 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 variants 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 the brain's signals cause 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.

Variants in the KCNA1 gene have been found to cause a range of signs and symptoms that affect the nervous system. In at least one family, isolated myokymia (continuous muscle twitching and spasms without episodes of ataxia) has been attributed to KCNA1 variants. Changes in this gene have also been identified in a small number of people with repeated seizures (epilepsy). Like the KCNA1 variants that cause episodic ataxia (described above), the variants 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 variants in this single gene can cause several different disorders of the nervous system.