Juvenile myoclonic epilepsy

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Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, is a fairly common form of idiopathic generalized epilepsy affecting up to 10% of the population. This disorder typically first manifests itself between the ages of 12 and 18 with myoclonus occurring early in the morning. Most patients also have tonic-clonic seizures and many also have absence seizures. Linkage studies have demonstrated at least 6 loci for JME, 4 with known causative genes. Most of these genes are ion channels with the one non-ion channel gene having been shown to affect ion channel currents.

Signs and symptoms

Signs of JME are myoclonus occurring early in the morning. This rarely results in patients falling, but rather dropping objects. Attacks of myoclonia is more common in the arms than the legs. Other seizure types such as generalized tonic-clonic and absence seizures can also occur.



CACNB4 encodes a calcium channel β subunit. Calcium_channel#.CE.B2_subunit|β subunits are important regulators of calcium channel current amplitude, voltage dependence, and also regulate channel trafficking. The β4 isoform encoded by CACNB4 is most prevalent in the cerebellum. In mice, a naturally occurring null mutation leads to the "lethargic" phenotype, which is similar to JME. There are at least two mutations in the β4 subunit associated with JME, C104F and R482X. When wild-type α1A and β4 subunits are expressed in oocytes they produce large barium|Ba2+ currents that inactivate slowly. Interestingly, incorporation of either of the mutant β4 subunit into channels instead of wild-type subunits produces currents that are larger by 30-40%. The R482X mutation also increases the rate of fast inactivation of the channel. Since these effects are subtle, it is believed that they are contributory rather than completely causative for JME.1









Other loci

There is also evidence linking a gene or genes on chromosome 15 (15q14) and chromosome 6 (6p21) to JME. Causative genes in this region, however, have not been shown.


Diagnosis is typically made based on patient history. EEG recordings are also used as confirmation.


See the equivalent section in the main epilepsy article.


  1. Escayg A, De Waard M, Lee D, Bichet D, Wolf P, Mayer T, Johnston J, Baloh R, Sander T, Meisler M (2000). "Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia.". Am J Hum Genet 66 (5): 1531-9. PMID 10762541.
  2. Cossette P, Liu L, Brisebois K, Dong H, Lortie A, Vanasse M, Saint-Hilaire J, Carmant L, Verner A, Lu W, Wang Y, Rouleau G (2002). "Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy.". Nat Genet 31 (2): 184-9. PMID 11992121.
  3. Gallagher M, Song L, Arain F, Macdonald R (2004). "The juvenile myoclonic epilepsy GABA(A) receptor alpha1 subunit mutation A322D produces asymmetrical, subunit position-dependent reduction of heterozygous receptor currents and alpha1 subunit protein expression.". J Neurosci 24 (24): 5570-8. PMID 15201329.
  4. Krampfl K, Maljevic S, Cossette P, Ziegler E, Rouleau G, Lerche H, Bufler J (2005). "Molecular analysis of the A322D mutation in the GABA receptor alpha-subunit causing juvenile myoclonic epilepsy.". Eur J Neurosci 22 (1): 10-20. PMID 16029191.
  5. Haug K, Warnstedt M, Alekov A, Sander T, Ramírez A, Poser B, Maljevic S, Hebeisen S, Kubisch C, Rebstock J, Horvath S, Hallmann K, Dullinger J, Rau B, Haverkamp F, Beyenburg S, Schulz H, Janz D, Giese B, Müller-Newen G, Propping P, Elger C, Fahlke C, Lerche H, Heils A (2003). "Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies.". Nat Genet 33 (4): 527-32. PMID 12612585.
  6. Dibbens L, Feng H, Richards M, Harkin L, Hodgson B, Scott D, Jenkins M, Petrou S, Sutherland G, Scheffer I, Berkovic S, Macdonald R, Mulley J (2004). "GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies.". Hum Mol Genet 13 (13): 1315-9. PMID 15115768.
  7. Feng H, Kang J, Song L, Dibbens L, Mulley J, Macdonald R (2006). "Delta subunit susceptibility variants E177A and R220H associated with complex epilepsy alter channel gating and surface expression of alpha4beta2delta GABAA receptors.". J Neurosci 26 (5): 1499-506. PMID 16452673.
  8. Lenzen K, Heils A, Lorenz S, Hempelmann A, Sander T (2005). "Association analysis of the Arg220His variation of the human gene encoding the GABA delta subunit with idiopathic generalized epilepsy.". Epilepsy Res 65 (1-2): 53-7. PMID 16023832.
  10. Suzuki T, Delgado-Escueta A, Alonso M, Morita R, Okamura N, Sugimoto Y, Bai D, Medina M, Bailey J, Rasmussen A, Ramos-Peek J, Cordova S, Rubio-Donnadieu F, Ochoa A, Jara-Prado A, Inazawa J, Yamakawa K (2006). "Mutation analyses of genes on 6p12-p11 in patients with juvenile myoclonic epilepsy.". Neurosci Lett 405 (1-2): 126-31. PMID 16876319.
  11. "Mutations in the GABRA1 and EFHC1 genes are rare in familial juvenile myoclonic epilepsy.". Epilepsy Res. PMID 16839746.
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