NORD gratefully acknowledges the KCNQ2 CURE Alliance and Kristen Park, MD, Assistant Professor, Department of Pediatrics, University of Colorado School of Medicine; Program Director for the Epilepsy Fellowship at Children's Hospital of Colorado, for assistance in the preparation of this report.
The gene that is altered in patients with KCNQ2E is the gene for a potassium channel within the brain, located on the long arm of chromosome 20, at position 13.3 (20p13.3).
Chromosomes are located in the nucleus of human cells and carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes numbered from 1 through 22 are called autosomes and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
KCNQ2 belongs to a family of other ion channel genes and is sometimes abbreviated Kv7.2. Ion channels are pores in the cell membrane that allow charged atoms (ions) to flow into and out of cells and play a key role in a cell’s ability to generate and transmit electrical signals. These genes share important properties and are named to reflect them. “K” is the chemical symbol for potassium which is a positively charged atom. CN is an abbreviation for channel. This gene is the 2nd member of the Q subfamily which indicates that the channel is voltage gated. This means that the channel opens according to the charge in its cellular environment. Mutations in the KCNQ2 gene cause a spectrum of disease that ranges from benign seizures in infancy to epileptic encephalopathy likely based on the degree of dysfunction in this channel. Those that cause encephalopathy are typically located in several particular areas; however, recent literature suggests that distinguishing presentations may be more complex than initially thought.
Epilepsy is estimated to affect 1 in 26 people during their lifetime with an incidence of approximately 44/100,000 people. The incidence is highest in young children and older adults with children often having the most severe types of epilepsies. The incidence of epilepsy in children under 2 years of age is estimated to be 70.1 per 100,000 based on a recent population based study conducted in North London. In this research, severe epilepsies associated with abnormal development and EEG (epileptic encephalopathies) were identified in 22 (39%) of 57 infants.
KCNQ2E affects males and females in equal numbers. Cases can go undiagnosed or misdiagnosed, making it difficult to determine the disorder’s true frequency in the general population. In addition, the recent discovery of this disorder likely means that older patients exist in the community who have not been tested or have been given another diagnosis. Several researchers have attempted to determine the frequency of this disorder by testing groups of children with undiagnosed seizure disorders sharing some of the features of KCNQ2E (neonatal onset, epileptic encephalopathy). In a group of 84 patients with neonatal or early infantile seizures and associated developmental impairment, mutations in KCNQ2 were identified in 11 patients (13%). In another group of 239 patients with early infantile epileptic encephalopathy (EIEE), 12 patients (5%) harbored mutations in the KCNQ2 gene.
KCNQ2E is considered an autosomal dominant disorder. Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. In some individuals, the disorder is due to a new (de novo) genetic mutation that occurs in the egg or sperm cell. In such situations, the disorder is not inherited from the parents. Most children with KCNQ2E have a de novo gene mutation; however, a small number have a gene mutation inherited from an unaffected or mildly affected parent in a pattern called mosaicism. This means that only some cells in the parent’s body contain a copy of the altered gene.
The diagnosis of KCNQ2E is ultimately made by molecular genetic testing. This can be done by examining only the potassium channel gene or by sending testing that looks for sequence changes in a number of genes associated with epilepsy in infancy.
Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, developmental pediatricians, and/or other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.
In some children, it is possible that treatment with anticonvulsant drugs may help reduce or control various types of seizure activity associated with KCNQ2E. Anticonvulsant medications have many different mechanisms of action and it is not entirely clear which medications are best for KCNQ2E. Some reports suggest that children respond best to medications which affect how sodium or potassium flow into nerve cells; however, the number of children reported may be too small to draw these conclusions. If seizures fail to respond to medication, other treatments including specialized diets, devices, and surgeries may be considered.
Clinical Testing and Work-up
One of the first steps in the evaluation of new onset seizures in an infant is to characterize the patterns of brain activity associated with the seizures. This is done by performing an electroencephalogram or EEG. This is a painless and non-invasive means of recording the patterns of electrical activity of the brain. Electrodes placed on the scalp pick up and record the electrical waves during periods of activity, sleep, and during seizures. KCNQ2E is often associated with a burst-suppression pattern on EEG but may have other non-specific abnormalities and is typically not normal between seizures, in contrast to BFNC.
When seizures present in infancy, there are a number of potential causes that may need to be excluded before genetic testing is pursued. This often depends on the presentation and other clinical factors. Tests that may be performed include evaluations for infection, electrolyte disturbance, metabolic disorders, and structural problems in the brain.
Magnetic Resonance Imaging (MRI) is a radiological technique that produces detailed images of cross-sections or slices of the brain by using a magnetic field. The images can provide information concerning any malformation of the brain structures or other types of lesions commonly seen in epilepsy.
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Contact for additional information about KCNQ2E:
Kristen Park, MD
Children’s Hospital of Colorado
Assistant Professor of Pediatrics
University of Colorado School of Medicine
Bureau, M., Genton, P., Dravet, C., Delgado-Escueta, A.V., Tassinari, C.A., Thomas, P., & Wolf, P. Epileptic Syndromes in Infancy, Childhood and Adolescence. (5th ed.). Paris, FR: John Libbey Eurotext; 2012.
Eltze, C. M., et al. A population-based study of newly diagnosed epilepsy in infants. Epilepsia 2013;54(3): 437-445.
Kato, M., et al. Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia 2013;54(7): 1282-1287.
Weckhuysen, S., et al. Extending the KCNQ2 encephalopathy spectrum: Clinical and neuroimaging findings in 17 patients.Neurology 2013;81(19): 1697-1703.
Weckhuysen, S., et al. KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol 2012;71(1): 15-25.
Nabbout, R. and O. Dulac. Epileptic encephalopathies: a brief overview. J Clin Neurophysiol 2003;20(6): 393-397.
Genetics Home Reference. US National Library of Medicine (NLM) and the National Institute of Health (NIH). KCNQ2. Last Reviewed: April 2013. https://ghr.nlm.nih.gov/gene/KCNQ2 Accessed March 7, 2016.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Epileptic Encephalopathy, Early Infantile, 7; EIEE7. Entry No: 613720. Last Edited: 3/18/2014. http://www.omim.org/entry/613720 Accessed March 7, 2016.
Bellini G, Miceli F, Soldovieri MV, et al. KCNQ2-Related Disorders. 2010 Apr 27 [Updated 2013 Apr 11]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.Available from: http://www.ncbi.nlm.nih.gov/books/NBK32534/ Accessed March 7, 2016.
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