KCNB1 encephalopathy is a condition characterized by abnormal brain function (encephalopathy), recurrent seizures (epilepsy), and developmental delay.

Most people who have KCNB1 encephalopathy have more than one type of seizure. The seizure types that can occur in people with this condition include uncontrolled muscle twitches (myoclonic seizures), uncontrolled muscle stiffness (tonic seizures), loss of consciousness with muscle rigidity and convulsions (tonic-clonic seizures), sudden episodes of weak muscle tone (atonic seizures), sudden falls (drop attacks), or partial or complete loss of consciousness (absence seizures).

Some individuals with KCNB1 encephalopathy do not develop seizures, but they do have an abnormal pattern of electrical activity in the brain called continuous spike and waves during slow-wave sleep (CSWS). This pattern occurs during sleep, specifically during deep (slow-wave) sleep.

Children with KCNB1 encephalopathy have delayed development of speech and motor skills, such as sitting, crawling, and walking. Weak muscle tone (hypotonia) in some affected individuals can contribute to this delay. Many children with the condition eventually walk independently, but some individuals require assistance. Some affected individuals can communicate verbally using simple sentences, while others never develop the skill.

About half of individuals with KCNB1 encephalopathy also have neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). In KCNB1 encephalopathy, problems with vision, digestion, and sleep can rarely occur.

As its name indicates, KCNB1 encephalopathy is caused by mutations in the KCNB1gene. The KCNB1 gene provides instructions for making one part of a potassium channel called Kv2.1. Potassium channels transport positively charged atoms (ions) of potassium in and out of cells. This activity plays a key role in a cell’s ability to generate and transmit electrical signals. Kv2.1 channels are found primarily in nerve cells (neurons) in the brain where they are involved in regulating activity of neurons and sending electrical signals in the brain.

Most KCNB1 gene mutations that cause KCNB1 encephalopathy lead to an altered protein that results in impaired Kv2.1 channel function. As a result, the channels cannot regulate the flow of potassium ions in neurons, which disrupts normal communication between these cells. Impaired channel function disrupts normal brain development and leads to seizures, intellectual disability, and other features of encephalopathy that occur in this condition.

Normal Function

The KCNB1 gene belongs to a large family of genes that provide instructions for making potassium channels. These channels, which transport positively charged atoms (ions) of potassium in and out of cells, play a key role in a cell's ability to generate and transmit electrical signals.

The KCNB1 gene provides instructions for making one part of a potassium channel called Kv2.1. These channels are found primarily in nerve cells (neurons) in the brain where they transport potassium ions out of neurons. The flow of ions through potassium channels in neurons plays a role in regulating the activity of neurons and sending electrical signals in the brain, allowing communication between these cells.

Health Conditions Related to Genetic Changes

KCNB1 encephalopathy

More than 45 mutations in the KCNB1 gene have been found to cause a condition called KCNB1 encephalopathy. This condition is characterized by abnormal brain function (encephalopathy), recurrent seizures (epilepsy), and developmental delay.

Most KCNB1 gene mutations change single protein building blocks (amino acids), altering the proteins. Other mutations introduce a premature stop signal in the instructions for making the protein, resulting in production of a shortened, nonfunctional protein. All KCNB1 gene mutations impair Kv2.1 channel function. Channels made with the abnormal proteins are unable to function, which reduces Kv2.1 channel function in the brain. As a result, the channels cannot regulate the flow of potassium ions in neurons, which disrupts normal communication between these cells. Impaired channel function disrupts normal brain development and leads to seizures, intellectual disability, and other features of encephalopathy that occur in this condition.

Other Names for This Gene

• DEE26
• DRK1
• Kv2.1
• potassium channel, voltage-gated, shab-related subfamily, member 1

Genomic Location

The KCNB1 gene is found on chromosome 20.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from a new mutation in the gene and occur in people with no history of the disorder in their family.

The prevalence of KCNB1 encephalopathy is unknown. More than 65 cases have been reported in the scientific literature.