Details of Disease

General Information of Disease (ID: DIS4709R)

• Disease Name: Absence seizure
• Synonyms: petit mal seizure; absence seizure; pyknolepsy
• Disease Class: 8A61-8A6Z: Epilepsy/seizure
• Definition: Childhood absence epilepsy (CAE) is a familial generalized pediatric epilepsy, characterized by very frequent (multiple per day) absence seizures, usually occurring in children between the ages of 4 and 10 years, with, in most cases, a good prognosis.
• Disease Hierarchy:
  DISD715V: Hereditary neurological disease
  DIS9O5K5: Childhood electroclinical syndrome
  DISJPOUD: Absence epilepsy
  DISYKM6G: Childhood-onset epilepsy syndrome
  DIS4709R: Absence seizure
• ICD Code:
  ICD-11: ICD-11: 8A68.2
  Expand ICD-11: '8A68.2
• Disease Identifiers:
  MONDO ID: MONDO_0010826
  MESH ID: D004832
  UMLS CUI: C4281785
  MedGen ID: 924120
  Orphanet ID: 64280
  SNOMED CT ID: 50866000

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Discontinued Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
SCH 50911	DMW9H4A	Terminated	Small molecular drug	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 16 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CACNA1G	TT729IR	Limited	Genetic Variation	[2]
GABRD	TTGXH6N	Limited	Biomarker	[3]
GRM4	TTICZ1O	Limited	Genetic Variation	[4]
HCN1	TTNB6UQ	Limited	Genetic Variation	[5]
KCNQ3	TTIVDM3	Limited	Biomarker	[6]
SLC6A1	TTPRKM0	Limited	Genetic Variation	[7]
CACNA1A	TTX4QDJ	Strong	Biomarker	[8]
CACNA1H	TTZPWGN	Strong	Biomarker	[8]
CACNA1I	TTQZFTH	Strong	Biomarker	[2]
CACNA2D2	TTU8P3M	Strong	Biomarker	[9]
CLCN2	TT30NW6	Strong	Genetic Variation	[10]
GABRA1	TT1MPAY	Strong	Genetic Variation	[11]
GABRA5	TTNZPQ1	Strong	Biomarker	[12]
GABRG2	TT06RH5	Strong	Genetic Variation	[13]
GJA8	TTJ7ATH	Strong	Genetic Variation	[14]
KCNK9	TTL4FMB	Strong	Biomarker	[15]

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
CACNG3	DTVFLQD	Limited	Biomarker	[16]
CACNA1H	DTUFAZ5	Supportive	Autosomal dominant	[17]
SLC2A1	DTG3T6X	Supportive	Autosomal dominant	[18]

This Disease Is Related to 10 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GABRA6	OTX4UC3O	Limited	Genetic Variation	[19]
LGI4	OTZGS8BN	Limited	Genetic Variation	[20]
NIPA2	OT4NEBNO	Limited	Genetic Variation	[21]
TCOF1	OT4BOYTM	Limited	Biomarker	[22]
TRAK1	OTMQVYNP	Limited	Altered Expression	[23]
CACNA1H	OTM705TH	Supportive	Autosomal dominant	[17]
GABRB3	OT80C3D4	Supportive	Autosomal dominant	[24]
SLC2A1	OTA675TJ	Supportive	Autosomal dominant	[18]
EFHC1	OTS9IBNE	Strong	Genetic Variation	[25]
JRK	OTO8E77P	Strong	Biomarker	[26]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1075).
• [2] Pharmacogenetics of antiepileptic drug efficacy in childhood absence epilepsy.Ann Neurol. 2017 Mar;81(3):444-453. doi: 10.1002/ana.24886.
• [3] Mutations in GABAA receptor subunits associated with genetic epilepsies.J Physiol. 2010 Jun 1;588(Pt 11):1861-9. doi: 10.1113/jphysiol.2010.186999. Epub 2010 Mar 22.
• [4] Role of GRM4 in idiopathic generalized epilepsies analysed by genetic association and sequence analysis.Epilepsy Res. 2010 May;89(2-3):319-26. doi: 10.1016/j.eplepsyres.2010.02.004. Epub 2010 Mar 24.
• [5] 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.
• [6] Localization of a gene for benign adult familial myoclonic epilepsy to chromosome 8q23.3-q24.1.Am J Hum Genet. 1999 Sep;65(3):745-51. doi: 10.1086/302535.
• [7] SLC6A1 variants identified in epilepsy patients reduce -aminobutyric acid transport.Epilepsia. 2018 Sep;59(9):e135-e141. doi: 10.1111/epi.14531. Epub 2018 Aug 21.
• [8] Adult loss of Cacna1a in mice recapitulates childhood absence epilepsy by distinct thalamic bursting mechanisms.Brain. 2020 Jan 1;143(1):161-174. doi: 10.1093/brain/awz365.
• [9] entla, a novel epileptic and ataxic Cacna2d2 mutant of the mouse.J Biol Chem. 2004 Feb 20;279(8):7322-30. doi: 10.1074/jbc.M308778200. Epub 2003 Dec 2.
• [10] De novo SCN1A, SCN8A, and CLCN2 mutations in childhood absence epilepsy.Epilepsy Res. 2019 Aug;154:55-61. doi: 10.1016/j.eplepsyres.2019.04.005. Epub 2019 Apr 22.
• [11] A mutation in the GABA(A) receptor alpha(1)-subunit is associated with absence epilepsy. Ann Neurol. 2006 Jun;59(6):983-7. doi: 10.1002/ana.20874.
• [12] Case-control study and transmission/disequilibrium tests of the genes encoding GABRA5 and GABRB3 in a Chinese population affected by childhood absence epilepsy.Chin Med J (Engl). 2004 Oct;117(10):1497-501.
• [13] Mutational screening of GABRG2 gene in Pakistani population of Punjab with generalized tonic clonic seizures and children with childhood absence epilepsy.J Chin Med Assoc. 2018 Aug;81(8):665-669. doi: 10.1016/j.jcma.2018.05.001. Epub 2018 Jun 19.
• [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] A TASK3 channel (KCNK9) mutation in a genetic model of absence epilepsy.J Mol Neurosci. 2005;25(1):37-51. doi: 10.1385/JMN:25:1:037.
• [16] Linkage and association analysis of CACNG3 in childhood absence epilepsy.Eur J Hum Genet. 2007 Apr;15(4):463-72. doi: 10.1038/sj.ejhg.5201783. Epub 2007 Jan 31.
• [17] Association between genetic variation of CACNA1H and childhood absence epilepsy. Ann Neurol. 2003 Aug;54(2):239-43. doi: 10.1002/ana.10607.
• [18] Early-onset absence epilepsy caused by mutations in the glucose transporter GLUT1. Ann Neurol. 2009 Sep;66(3):415-9. doi: 10.1002/ana.21724.
• [19] The GABRA6 mutation, R46W, associated with childhood absence epilepsy, alters 622 and 62 GABA(A) receptor channel gating and expression.J Physiol. 2011 Dec 1;589(Pt 23):5857-78. doi: 10.1113/jphysiol.2011.218883. Epub 2011 Sep 19.
• [20] Genotypic association of exonic LGI4 polymorphisms and childhood absence epilepsy.Neurogenetics. 2004 Feb;5(1):41-4. doi: 10.1007/s10048-003-0158-8. Epub 2003 Sep 19.
• [21] The absence of NIPA2 enhances neural excitability through BK (big potassium) channels.CNS Neurosci Ther. 2019 Aug;25(8):865-875. doi: 10.1111/cns.13119. Epub 2019 Mar 20.
• [22] Genetic architecture of idiopathic generalized epilepsy: clinical genetic analysis of 55 multiplex families.Epilepsia. 2004 May;45(5):467-78. doi: 10.1111/j.0013-9580.2004.46803.x.
• [23] Hypertonia-linked protein Trak1 functions with mitofusins to promote mitochondrial tethering and fusion.Protein Cell. 2018 Aug;9(8):693-716. doi: 10.1007/s13238-017-0469-4. Epub 2017 Sep 18.
• [24] Hyperglycosylation and reduced GABA currents of mutated GABRB3 polypeptide in remitting childhood absence epilepsy. Am J Hum Genet. 2008 Jun;82(6):1249-61. doi: 10.1016/j.ajhg.2008.04.020.
• [25] Progress in mapping human epilepsy genes.Epilepsia. 1994;35 Suppl 1:S29-40. doi: 10.1111/j.1528-1157.1994.tb05926.x.
• [26] 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.