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 behavioral conditions, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). ADHD is characterized by overactivity, impulsive behavior, and difficulty paying attention. In KCNB1 encephalopathy, problems with vision, digestion, and sleep can rarely occur.
The prevalence of KCNB1 encephalopathy is unknown. More than 65 cases have been reported in the scientific literature.
As its name indicates, KCNB1 encephalopathy is caused by mutations in the KCNB1 gene. 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.
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.
Other Names for This Condition
- Early infantile epileptic encephalopathy 26
- Epileptic encephalopathy, early infantile, 26
- KCNB1-related epilepsy
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Research Studies from ClinicalTrials.gov
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
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- Kang SK, Vanoye CG, Misra SN, Echevarria DM, Calhoun JD, O'Connor JB, Fabre KL, McKnight D, Demmer L, Goldenberg P, Grote LE, Thiffault I, Saunders C, Strauss KA, Torkamani A, van der Smagt J, van Gassen K, Carson RP, Diaz J, Leon E, Jacher JE, Hannibal MC, Litwin J, Friedman NR, Schreiber A, Lynch B, Poduri A, Marsh ED, Goldberg EM, Millichap JJ, George AL Jr, Kearney JA. Spectrum of K(V) 2.1 Dysfunction in KCNB1-Associated Neurodevelopmental Disorders. Ann Neurol. 2019 Dec;86(6):899-912. doi: 10.1002/ana.25607. Epub 2019 Oct 24. Citation on PubMed
- Marini C, Romoli M, Parrini E, Costa C, Mei D, Mari F, Parmeggiani L, Procopio E, Metitieri T, Cellini E, Virdò S, De Vita D, Gentile M, Prontera P, Calabresi P, Guerrini R. Clinical features and outcome of 6 new patients carrying de novo KCNB1 gene mutations. Neurol Genet. 2017 Dec 11;3(6):e206. doi: 10.1212/NXG.0000000000000206. eCollection 2017 Dec. Citation on PubMed
- Torkamani A, Bersell K, Jorge BS, Bjork RL Jr, Friedman JR, Bloss CS, Cohen J, Gupta S, Naidu S, Vanoye CG, George AL Jr, Kearney JA. De novo KCNB1 mutations in epileptic encephalopathy. Ann Neurol. 2014 Oct;76(4):529-540. doi: 10.1002/ana.24263. Epub 2014 Sep 19. Citation on PubMed