Juvenile myoclonic epilepsy is a condition characterized by recurrent seizures (epilepsy). This condition begins in childhood or adolescence, usually between ages 12 and 18, and lasts into adulthood. The most common type of seizure in people with this condition is myoclonic seizures, which cause rapid, uncontrolled muscle jerks. People with this condition may also have generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Sometimes, affected individuals have absence seizures, which cause loss of consciousness for a short period that appears as a staring spell. Typically, people with juvenile myoclonic epilepsy develop the characteristic myoclonic seizures in adolescence, then develop generalized tonic-clonic seizures a few years later. Although seizures can happen at any time, they occur most commonly in the morning, shortly after awakening. Seizures can be triggered by a lack of sleep, extreme tiredness, stress, or alcohol consumption.

Juvenile myoclonic epilepsy affects an estimated 1 in 1,000 people worldwide. Approximately 5 percent of people with epilepsy have juvenile myoclonic epilepsy.

The genetics of juvenile myoclonic epilepsy are complex and not completely understood. Mutations in one of several genes can cause or increase susceptibility to this condition. The most studied of these genes are the GABRA1 gene and the EFHC1 gene, although mutations in at least three other genes have been identified in people with this condition. Many people with juvenile myoclonic epilepsy do not have mutations in any of these genes. Changes in other, unidentified genes are likely involved in this condition.

A mutation in the GABRA1 gene has been identified in several members of a large family with juvenile myoclonic epilepsy. The GABRA1 gene provides instructions for making one piece, the alpha-1 (α1) subunit, of the GABA_A receptor protein. The GABA_A receptor acts as a channel that allows negatively charged chlorine atoms (chloride ions) to cross the cell membrane. After infancy, the influx of chloride ions creates an environment in the cell that inhibits signaling between nerve cells (neurons) and prevents the brain from being overloaded with too many signals. Mutations in the GABRA1 gene lead to an altered α1 subunit and a decrease in the number of GABA_A receptors available. As a result, the signaling between neurons is not controlled, which can lead to overstimulation of neurons. Researchers believe that the overstimulation of certain neurons in the brain triggers the abnormal brain activity associated with seizures.

Mutations in the EFHC1 gene have been associated with juvenile myoclonic epilepsy in a small number of people. The EFHC1 gene provides instructions for making a protein that also plays a role in neuron activity, although its function is not completely understood. The EFHC1 protein is attached to another protein that acts as a calcium channel. This protein allows positively charged calcium ions to cross the cell membrane. The movement of these ions is critical for normal signaling between neurons. The EFHC1 protein is thought to help regulate the balance of calcium ions inside the cell, although the mechanism is unclear. In addition, studies show that the EFHC1 protein may be involved in the self-destruction of cells. EFHC1 gene mutations reduce the function of the EFHC1 protein. Researchers suggest that this reduction causes an increase in the number of neurons and disrupts the calcium balance. Together, these effects may lead to overstimulation of neurons and trigger seizures.

Genetic Testing Information

• Genetic Testing Registry: Epilepsy, idiopathic generalized, susceptibility to, 10
• Genetic Testing Registry: Epilepsy, idiopathic generalized, susceptibility to, 11
• Genetic Testing Registry: Epilepsy, idiopathic generalized, susceptibility to, 13
• Genetic Testing Registry: Epilepsy, idiopathic generalized, susceptibility to, 9
• Genetic Testing Registry: Juvenile myoclonic epilepsy

Genetic and Rare Diseases Information Center

• Juvenile myoclonic epilepsy

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• EPILEPSY, MYOCLONIC JUVENILE; EJM
• EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 11; EIG11
• EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 9; EIG9
• EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 13; EIG13
• EPILEPSY, JUVENILE MYOCLONIC, SUSCEPTIBILITY TO, 9; EJM9
• EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 10; EIG10

Scientific Articles on PubMed

• PubMed

• Cossette P, Liu L, Brisebois K, Dong H, Lortie A, Vanasse M, Saint-Hilaire JM, Carmant L, Verner A, Lu WY, Wang YT, Rouleau GA. Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat Genet. 2002 Jun;31(2):184-9. doi: 10.1038/ng885. Epub 2002 May 6. Citation on PubMed
• Ding L, Feng HJ, Macdonald RL, Botzolakis EJ, Hu N, Gallagher MJ. GABA(A) receptor alpha1 subunit mutation A322D associated with autosomal dominant juvenile myoclonic epilepsy reduces the expression and alters the composition of wild type GABA(A) receptors. J Biol Chem. 2010 Aug 20;285(34):26390-405. doi: 10.1074/jbc.M110.142299. Epub 2010 Jun 15. Citation on PubMed or Free article on PubMed Central
• Gallagher MJ, Ding L, Maheshwari A, Macdonald RL. The GABAA receptor alpha1 subunit epilepsy mutation A322D inhibits transmembrane helix formation and causes proteasomal degradation. Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):12999-3004. doi: 10.1073/pnas.0700163104. Epub 2007 Aug 1. Citation on PubMed or Free article on PubMed Central
• Krampfl K, Maljevic S, Cossette P, Ziegler E, Rouleau GA, Lerche H, Bufler J. Molecular analysis of the A322D mutation in the GABA receptor alpha-subunit causing juvenile myoclonic epilepsy. Eur J Neurosci. 2005 Jul;22(1):10-20. doi: 10.1111/j.1460-9568.2005.04168.x. Citation on PubMed
• Suzuki T, Delgado-Escueta AV, Aguan K, Alonso ME, Shi J, Hara Y, Nishida M, Numata T, Medina MT, Takeuchi T, Morita R, Bai D, Ganesh S, Sugimoto Y, Inazawa J, Bailey JN, Ochoa A, Jara-Prado A, Rasmussen A, Ramos-Peek J, Cordova S, Rubio-Donnadieu F, Inoue Y, Osawa M, Kaneko S, Oguni H, Mori Y, Yamakawa K. Mutations in EFHC1 cause juvenile myoclonic epilepsy. Nat Genet. 2004 Aug;36(8):842-9. doi: 10.1038/ng1393. Epub 2004 Jul 18. Citation on PubMed