Details of Disease

General Information of Disease (ID: DISYXV1N)

• Disease Name: Juvenile myoclonic epilepsy
• Synonyms: petit mal, impulsive; myoclonic epilepsy, juvenile, susceptibility to, 1; Janz syndrome; EJM; myoclonic epilepsy, juvenile, 1; myoclonic epilepsy, juvenile; juvenile myoclonus epilepsy; epilepsy, myoclonic juvenile; JME
• Definition: Juvenile myoclonic epilepsy is the most common hereditary idiopathic generalized epilepsy syndrome and is characterized by myoclonic jerks of the upper limbs on awakening, generalized tonic-clonic seizures manifesting during adolescence and triggered by sleep deprivation, alcohol intake, and cognitive activities, and typical absence seizures (30% of cases).
• Disease Hierarchy:
  DISHLPYW: Familial partial epilepsy
  DIS9O5K5: Childhood electroclinical syndrome
  DISZRK1H: Adolescent/adult-onset epilepsy syndrome
  DISOJJ2D: Movement disorder
  DIS5B2FL: Adolescence-adult electroclinical syndrome
  DISYXV1N: Juvenile myoclonic epilepsy
• Disease Identifiers:
  MONDO ID: MONDO_0009696
  MESH ID: D020190
  UMLS CUI: C0270853
  OMIM ID: 254770
  MedGen ID: 78738
  Orphanet ID: 307
  SNOMED CT ID: 6204001

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 20 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CFP	TTLA0VS	Limited	Biomarker	[1]
GABRD	TTGXH6N	Limited	Genetic Variation	[2]
HCN2	TT9EUT4	Limited	Genetic Variation	[3]
GABRA1	TT1MPAY	Supportive	Autosomal dominant	[4]
GABRA5	TTNZPQ1	moderate	Biomarker	[5]
GJD2	TTOZAFI	moderate	Genetic Variation	[6]
SCN1A	TTANOZH	moderate	Genetic Variation	[7]
SLC12A5	TTH6UZY	moderate	Posttranslational Modification	[8]
SLC12A6	TT8DFHE	moderate	Biomarker	[9]
ALDH5A1	TTJUWVB	Strong	Genetic Variation	[10]
CHRNA4	TT4H1MQ	Strong	Altered Expression	[11]
CLCN2	TT30NW6	Strong	SusceptibilityMutation	[4]
CTF1	TTXGTZU	Strong	Genetic Variation	[12]
GABRA1	TT1MPAY	Strong	Genetic Variation	[13]
GABRG2	TT06RH5	Strong	Genetic Variation	[2]
GJA8	TTJ7ATH	Strong	Genetic Variation	[14]
KCND3	TTPLQO0	Strong	Genetic Variation	[15]
KCNQ2	TTPXI3S	Strong	Genetic Variation	[16]
KCNQ3	TTIVDM3	Strong	Biomarker	[17]
TRPM2	TTEBMN7	Strong	Biomarker	[18]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
CACNB4	DTV8E46	Supportive	Autosomal dominant	[4]
CACNB4	DTV8E46	Strong	Genetic Variation	[19]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
MMEL1	DEYCUQ2	moderate	Biomarker	[20]

This Disease Is Related to 19 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CPA6	OT43RD23	Limited	Genetic Variation	[21]
EFHC1	OTS9IBNE	Limited	Autosomal dominant	[22]
TOP3B	OTNFEUOO	Limited	Biomarker	[23]
CACNB4	OTYAI1UO	Supportive	Autosomal dominant	[4]
CILK1	OTWOYEYP	Supportive	Autosomal dominant	[24]
GABRA1	OTC2W96H	Supportive	Autosomal dominant	[4]
HLA-F	OT76CM19	moderate	Genetic Variation	[25]
LRRC1	OTSVD30Q	moderate	Biomarker	[26]
MED19	OTT9RT5N	moderate	Biomarker	[18]
PLXNB1	OTCA7JIT	moderate	Biomarker	[20]
TFAP2B	OTR1T8E9	moderate	Biomarker	[27]
DHX40	OTOL02QN	Strong	Biomarker	[28]
EFHC2	OTI459M8	Strong	Biomarker	[29]
GABRB3	OT80C3D4	Strong	Genetic Variation	[30]
JRK	OTO8E77P	Strong	Biomarker	[31]
ME2	OTO4LL76	Strong	Genetic Variation	[32]
NPL	OTA7P0TO	Strong	Genetic Variation	[33]
BCL9	OTRBIPR4	Definitive	Genetic Variation	[2]
LGSN	OTQG5Z82	Definitive	Genetic Variation	[2]

References

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• [2] Association of GABAA Receptor Gene with Epilepsy Syndromes.J Mol Neurosci. 2018 Jun;65(2):141-153. doi: 10.1007/s12031-018-1081-7. Epub 2018 May 21.
• [3] Case-control pharmacogenetic study of HCN1/HCN2 variants and genetic generalized epilepsies.Clin Exp Pharmacol Physiol. 2018 Mar;45(3):226-233. doi: 10.1111/1440-1681.12877. Epub 2017 Nov 28.
• [4] The quest for juvenile myoclonic epilepsy genes. Epilepsy Behav. 2013 Jul;28 Suppl 1:S52-7. doi: 10.1016/j.yebeh.2012.06.033.
• [5] Lack of association between juvenile myoclonic epilepsy and GABRA5 and GABRB3 genes.Am J Med Genet. 1997 Apr 18;74(2):150-3.
• [6] Genetic susceptibility in Juvenile Myoclonic Epilepsy: Systematic review of genetic association studies.PLoS One. 2017 Jun 21;12(6):e0179629. doi: 10.1371/journal.pone.0179629. eCollection 2017.
• [7] Whole exome sequencing identifies a novel SCN1A mutation in genetic (idiopathic) generalized epilepsy and juvenile myoclonic epilepsy subtypes.Neurol Sci. 2020 Mar;41(3):591-598. doi: 10.1007/s10072-019-04122-9. Epub 2019 Nov 13.
• [8] Methylation of cation-chloride cotransporters NKCC1 and KCC2 in patients with juvenile myoclonic epilepsy.Neurol Sci. 2019 May;40(5):1007-1013. doi: 10.1007/s10072-019-03743-4. Epub 2019 Feb 13.
• [9] Cloning, characterization, and chromosomal location of a novel human K+-Cl- cotransporter.J Biol Chem. 1999 Apr 9;274(15):10661-7. doi: 10.1074/jbc.274.15.10661.
• [10] Candidate gene analysis of the succinic semialdehyde dehydrogenase gene (ALDH5A1) in patients with idiopathic generalized epilepsy and photosensitivity.Neurosci Lett. 2006 Apr 24;397(3):234-9. doi: 10.1016/j.neulet.2005.12.030. Epub 2006 Jan 6.
• [11] Pathologic role of neuronal nicotinic acetylcholine receptors in epileptic disorders: implication for pharmacological interventions.Rev Neurosci. 2015;26(2):199-223. doi: 10.1515/revneuro-2014-0044.
• [12] Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies.Nat Commun. 2018 Dec 10;9(1):5269. doi: 10.1038/s41467-018-07524-z.
• [13] Subtle Brain Developmental Abnormalities in the Pathogenesis of Juvenile Myoclonic Epilepsy.Front Cell Neurosci. 2019 Sep 27;13:433. doi: 10.3389/fncel.2019.00433. eCollection 2019.
• [14] The cognitive phenotype of idiopathic generalized epilepsy.Epilepsy Behav. 2018 Dec;89:99-104. doi: 10.1016/j.yebeh.2018.10.007. Epub 2018 Nov 6.
• [15] Genetic abnormalities underlying familial epilepsy syndromes.Brain Dev. 2002 Jun;24(4):211-22. doi: 10.1016/s0387-7604(02)00056-6.
• [16] Evidence favoring genetic heterogeneity for febrile convulsions.Epilepsia. 2000 Feb;41(2):132-9. doi: 10.1111/j.1528-1157.2000.tb00132.x.
• [17] Genetic association analysis of KCNQ3 and juvenile myoclonic epilepsy in a South Indian population.Hum Genet. 2003 Oct;113(5):461-3. doi: 10.1007/s00439-003-1003-8. Epub 2003 Aug 20.
• [18] EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality.Genet Med. 2017 Feb;19(2):144-156. doi: 10.1038/gim.2016.86. Epub 2016 Jul 28.
• [19] The juvenile myoclonic epilepsy mutant of the calcium channel (4) subunit displays normal nuclear targeting in nerve and muscle cells.Channels (Austin). 2014;8(4):334-43. doi: 10.4161/chan.29322.
• [20] Somatosensory evoked potentials and EEG findings in siblings of juvenile myoclonic epilepsy patients.Epileptic Disord. 1999 Sep;1(3):173-7.
• [21] Novel carboxypeptidase A6 (CPA6) mutations identified in patients with juvenile myoclonic and generalized epilepsy.PLoS One. 2015 Apr 13;10(4):e0123180. doi: 10.1371/journal.pone.0123180. eCollection 2015.
• [22] Mutations in EFHC1 cause juvenile myoclonic epilepsy. Nat Genet. 2004 Aug;36(8):842-9. doi: 10.1038/ng1393. Epub 2004 Jul 18.
• [23] TOP3B: A Novel Candidate Gene in Juvenile Myoclonic Epilepsy?.Cytogenet Genome Res. 2018;154(1):1-5. doi: 10.1159/000486945. Epub 2018 Feb 28.
• [24] Variant Intestinal-Cell Kinase in Juvenile Myoclonic Epilepsy. N Engl J Med. 2018 Mar 15;378(11):1018-1028. doi: 10.1056/NEJMoa1700175.
• [25] Mapping, genomic structure, and polymorphisms of the human GABABR1 receptor gene: evaluation of its involvement in idiopathic generalized epilepsy.Neurogenetics. 1998 Dec;2(1):47-54. doi: 10.1007/s100480050051.
• [26] Identification and mutational analysis of candidate genes for juvenile myoclonic epilepsy on 6p11-p12: LRRC1, GCLC, KIAA0057 and CLIC5.Epilepsy Res. 2002 Aug;50(3):265-75. doi: 10.1016/s0920-1211(02)00052-9.
• [27] Mutation analyses of genes on 6p12-p11 in patients with juvenile myoclonic epilepsy.Neurosci Lett. 2006 Sep 11;405(1-2):126-31. doi: 10.1016/j.neulet.2006.06.038. Epub 2006 Jul 28.
• [28] Neuroimaging-based brain-age prediction in diverse forms of epilepsy: a signature of psychosis and beyond.Mol Psychiatry. 2021 Mar;26(3):825-834. doi: 10.1038/s41380-019-0446-9. Epub 2019 Jun 3.
• [29] EF-hand domain containing 2 (Efhc2) is crucial for distal segmentation of pronephros in zebrafish.Cell Biosci. 2018 Oct 16;8:53. doi: 10.1186/s13578-018-0253-z. eCollection 2018.
• [30] Seizures of idiopathic generalized epilepsies.Epilepsia. 2005;46 Suppl 9:34-47. doi: 10.1111/j.1528-1167.2005.00312.x.
• [31] Polymorphism analysis of JRK/JH8, the human homologue of mouse jerky, and description of a rare mutation in a case of CAE evolving to JME.Epilepsy Res. 2001 Aug;46(2):157-67. doi: 10.1016/s0920-1211(01)00275-3.
• [32] Sacred disease secrets revealed: the genetics of human epilepsy.Hum Mol Genet. 2005 Oct 15;14 Spec No. 2:2491-2500.
• [33] The gene encoding the alpha1A-voltage-dependent calcium channel (CACN1A4) is not a candidate for causing common subtypes of idiopathic generalized epilepsy.Epilepsy Res. 1998 Jan;29(2):115-22. doi: 10.1016/s0920-1211(97)00073-9.