Details of Disease

General Information of Disease (ID: DISZSKDG)

Disease Name Infantile spasm
Synonyms
infantile epileptic encephalopathy; epileptic encephalopathy, early infantile; infantile spasm; early infantile epileptic encephalopathy; early infantile epileptic encephalopathy with suppression-bursts; EIEE; DEE; early infantile epileptic encephalopathy with burst-suppression; developmental and epileptic encephalopathy; Ohtahara syndrome; epileptic encephalopathy, infantile
Disease Class 8A62: Epileptic encephalopathy
Definition
A complex neurodevelopmental disorder characterized by a range of developmental delays and epileptic encephalopathy phenotypes. Seizure onset is variable and intellectual disability is variable in presence and severity.|Individuals, both male and female, have been reported with variants in the GABRB3 gene. De novo and familial cases have been reported, with mostly missense and a few nonsense variants identified as causative. These patients have been described in the literature as having a range of phenotypes characterized as epileptic encephalopathy, Lennox-Gastaut syndrome, Dravet syndrome-like, and childhood absence epilepsy. Severity of intellectual disability is variable among reported probands, as is the age of onset of seizure phenotypes. In one case of epileptic encephalopathy, for example, the individual presented with severe intellectual disability while seizures onset at 12 years old. Additionally, individuals have been reported with the same de novo missense variants, and have been described with varying phenotypes.
Disease Hierarchy
DISYOKTG: Mendelian neurodevelopmental disorder
DISB9AFI: Complex neurodevelopmental disorder
DISRFC3B: Neonatal/infantile epilepsy syndrome
DISODZC9: Epilepsy, idiopathic generalized
DISZSKDG: Infantile spasm
ICD Code
ICD-11
ICD-11: 8A62.0
Disease Identifiers
MONDO ID
MONDO_0100062
UMLS CUI
C0393706
MedGen ID
97959
Orphanet ID
1934
SNOMED CT ID
230429005

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)
This Disease is Treated as An Indication in 2 Approved Drug(s)
Drug Name Drug ID Highest Status Drug Type REF
Cannabidiol DM0659E Approved Small molecular drug [1]
Vigabatrin DMYT0OG Approved Small molecular drug [2]
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This Disease is Treated as An Indication in 3 Clinical Trial Drug(s)
Drug Name Drug ID Highest Status Drug Type REF
CPP-115 DMK9NQI Phase 2 Small molecular drug [1]
ANAVEX 2-73 DM67OU4 Phase 1 NA [1]
CPP -15 DMQCHU3 Phase 1 NA [3]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 47 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
USP8 OTOXC2IP Limited Autosomal dominant [4]
WWOX OTBDGSMG Definitive Autosomal recessive [5]
ARHGEF15 OTGHDJFP Limited Autosomal dominant [4]
ATP6V0C OTKPL09B Limited Autosomal dominant [4]
CACNA2D1 OT5YLZIH Limited Autosomal dominant [4]
CAMK2G OTHD9KJG Limited Autosomal dominant [4]
CSNK1E OTF0UXX6 Limited Autosomal dominant [4]
RYR3 OT4EHIP4 Limited Autosomal dominant [5]
SLC12A5 OTBA2M8Y Limited Autosomal recessive [5]
ST7 OTZG8RC6 Limited Autosomal recessive [4]
CASK OT8EF7ZF Supportive Autosomal dominant [10]
CDKL5 OTGL5HRV Supportive Autosomal dominant [11]
DMXL2 OTB4JWN3 Supportive Autosomal dominant [12]
KCNA1 OTP3CCEH Supportive Autosomal dominant [6]
NEUROD2 OTJMMX9K Supportive Autosomal dominant [13]
PIGP OTGYAH4X Supportive Autosomal dominant [14]
PIGQ OTOD93DQ Supportive Autosomal dominant [15]
PNKP OTXJNXVW Supportive Autosomal dominant [7]
SCN2A OTUSYE4Z Supportive Autosomal dominant [8]
SIK1 OT6FCHME Supportive Autosomal dominant [9]
TRIM8 OTS6JFR0 Supportive Autosomal dominant [16]
ABAT OTXAGR7J Moderate Autosomal recessive [5]
CSTB OT3U0JF8 Moderate Autosomal recessive [5]
CUX2 OTDJTQAJ Moderate Autosomal dominant [5]
NECAP1 OTH49JRW Moderate Autosomal recessive [5]
SCN1A OTJ9ZTYI Strong Autosomal dominant [5]
ALG13 OTOH9PMY Definitive X-linked [5]
ARX OTBGYH25 Definitive X-linked [5]
CACNA1E OTHATMLU Definitive Autosomal dominant [5]
DNM1 OTI8X2WQ Definitive Autosomal dominant [5]
DOCK7 OTINNVQV Definitive Autosomal recessive [5]
FGF12 OTBM9QIO Definitive Autosomal dominant [5]
GABRA1 OTC2W96H Definitive Autosomal dominant [5]
GABRB3 OT80C3D4 Definitive Autosomal dominant [5]
GNAO1 OTPB1RGK Definitive Autosomal dominant [5]
ITPA OTQ47WVR Definitive Autosomal recessive [5]
KCNA2 OT18SUP8 Definitive Autosomal dominant [5]
KCNC2 OTGUNHB3 Definitive Autosomal dominant [5]
PLCB1 OT9HYT7A Definitive Autosomal recessive [5]
SCN1B OTGD78J3 Definitive Autosomal recessive [5]
SCN3A OT4C2LCB Definitive Autosomal dominant [5]
SLC25A22 OTQGVI1N Definitive Autosomal recessive [5]
SNAP25 OTUIQ81Q Definitive Autosomal dominant [5]
SPTAN1 OT6VY3A3 Definitive Autosomal dominant [5]
STXBP1 OTRYA8C3 Definitive Autosomal dominant [5]
SYNJ1 OTTE02XC Definitive Autosomal recessive [5]
SZT2 OTB4FVP4 Definitive Autosomal recessive [5]
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⏷ Show the Full List of 47 DOT(s)
This Disease Is Related to 14 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
CACNA2D1 TTFK1JQ Limited Autosomal dominant [4]
CSNK1E TTA8PLI Limited Autosomal dominant [4]
USP8 TT1J07C Limited Autosomal dominant [4]
KCNA1 TTS3DIK Supportive Autosomal dominant [6]
PNKP TTHR3IE Supportive Autosomal dominant [7]
SCN2A TTLJTUF Supportive Autosomal dominant [8]
SIK1 TT1H6LC Supportive Autosomal dominant [9]
ABAT TTT2LD9 Moderate Autosomal recessive [5]
GABRA1 TT1MPAY Definitive Autosomal dominant [5]
KCNA2 TTVFB0O Definitive Autosomal dominant [5]
KCNC2 TTGK3ZO Definitive Autosomal dominant [5]
PLCB1 TTLPGU7 Definitive Autosomal recessive [5]
SCN3A TTAXZ0K Definitive Autosomal dominant [5]
SNAP25 TTYQWA0 Definitive Autosomal dominant [5]
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⏷ Show the Full List of 14 DTT(s)
This Disease Is Related to 4 DTP Molecule(s)
Gene Name DTP ID Evidence Level Mode of Inheritance REF
SLC12A5 DTD62VB Limited Autosomal recessive [5]
SCN1A DTN0M1I Strong Autosomal dominant [5]
CACNA1E DTP9XH7 Definitive Autosomal dominant [5]
SLC25A22 DTJCWP8 Definitive Autosomal recessive [5]
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References

1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2 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: 4821).
3 Clinical pipeline report, company report or official report of Catalyst Pharma.
4 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
5 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
6 De novo KCNA1 variants in the PVP motif cause infantile epileptic encephalopathy and cognitive impairment similar to recurrent KCNA2 variants. Am J Med Genet A. 2018 Aug;176(8):1748-1752. doi: 10.1002/ajmg.a.38840. Epub 2018 Jul 28.
7 Mutations in PNKP cause microcephaly, seizures and defects in DNA repair. Nat Genet. 2010 Mar;42(3):245-9. doi: 10.1038/ng.526. Epub 2010 Jan 31.
8 Whole genome sequencing identifies SCN2A mutation in monozygotic twins with Ohtahara syndrome and unique neuropathologic findings. Epilepsia. 2013 May;54(5):e81-5. doi: 10.1111/epi.12137. Epub 2013 Mar 28.
9 De novo mutations in SIK1 cause a spectrum of developmental epilepsies. Am J Hum Genet. 2015 Apr 2;96(4):682-90. doi: 10.1016/j.ajhg.2015.02.013.
10 CASK Disorders. 2013 Nov 26 [updated 2020 May 21]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
11 Genes of early-onset epileptic encephalopathies: from genotype to phenotype. Pediatr Neurol. 2012 Jan;46(1):24-31. doi: 10.1016/j.pediatrneurol.2011.11.003.
12 Biallelic DMXL2 mutations impair autophagy and cause Ohtahara syndrome with progressive course. Brain. 2019 Dec 1;142(12):3876-3891. doi: 10.1093/brain/awz326.
13 De novo pathogenic variants in neuronal differentiation factor 2 (NEUROD2) cause a form of early infantile epileptic encephalopathy. J Med Genet. 2019 Feb;56(2):113-122. doi: 10.1136/jmedgenet-2018-105322. Epub 2018 Oct 15.
14 Compound heterozygous mutations in the gene PIGP are associated with early infantile epileptic encephalopathy. Hum Mol Genet. 2017 May 1;26(9):1706-1715. doi: 10.1093/hmg/ddx077.
15 Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis. Hum Mol Genet. 2014 Jun 15;23(12):3200-11. doi: 10.1093/hmg/ddu030. Epub 2014 Jan 25.
16 Further delineation of the clinical spectrum of de novo TRIM8 truncating mutations. Am J Med Genet A. 2018 Nov;176(11):2470-2478. doi: 10.1002/ajmg.a.40357. Epub 2018 Sep 23.