Details of Disease

Disease Name

Epileptic encephalopathy

Disease Class

8A62: Epileptic encephalopathy

Disease Hierarchy

DIS01GPL: Grass pollen hypersensitivity

DISZOCA3: Epileptic encephalopathy

ICD-11

ICD-11: 8A62

Disease Identifiers

MONDO ID

MONDO_0100062

UMLS CUI

C0393706

MedGen ID

97959

HPO ID

HP:0200134

Orphanet ID

1934

SNOMED CT ID

230429005

General Information of Disease (ID: DISZOCA3)

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 2 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
NBI-921352	DMTTW9V	Phase 2	Small molecule	[1]
PRAX-562	DMWUG4L	Phase 2	Small molecule	[2]
------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 10 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SIK1	TT1H6LC	Limited	Biomarker	[3]
KCNA1	TTS3DIK	Strong	GermlineCausalMutation	[4]
KCNQ2	TTPXI3S	Strong	Genetic Variation	[5]
KCNT1	TTGJFK1	Strong	Biomarker	[6]
PNKP	TTHR3IE	Strong	GermlineCausalMutation	[7]
PPP2CA	TTHTKNY	Strong	Biomarker	[8]
SCN1A	TTANOZH	Strong	Biomarker	[9]
SCN2A	TTLJTUF	Strong	Genetic Variation	[10]
DNM1	TTE3JW9	Definitive	Biomarker	[11]
GNAO1	TTAXD8Z	Definitive	Biomarker	[12]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A22	DTJCWP8	Strong	GermlineCausalMutation	[13]
------------------------------------------------------------------------------------

This Disease Is Related to 16 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MID1	OTWN1PGU	Limited	Genetic Variation	[14]
TOPBP1	OT6UPZPD	Limited	Biomarker	[15]
BRAT1	OT5ABVYX	Strong	Genetic Variation	[16]
CALN1	OTN2XE4T	Strong	Altered Expression	[17]
CASK	OT8EF7ZF	Strong	GermlineCausalMutation	[18]
CDKL5	OTGL5HRV	Strong	GermlineCausalMutation	[19]
DMXL2	OTB4JWN3	Strong	Genetic Variation	[20]
HERC6	OT7G9PQE	Strong	Biomarker	[21]
IBSP	OT29944Y	Strong	Genetic Variation	[22]
PIF1	OTUHKKVP	Strong	Biomarker	[23]
PIGP	OTGYAH4X	Strong	GermlineCausalMutation	[24]
PIGQ	OTOD93DQ	Strong	Genetic Variation	[25]
SHC3	OT305NPA	Strong	Biomarker	[26]
SOX18	OTPUMHWA	Strong	Altered Expression	[21]
TRIM8	OTS6JFR0	Strong	GermlineCausalMutation	[27]
NEUROD2	OTJMMX9K	Definitive	GermlineCausalMutation	[28]
------------------------------------------------------------------------------------


⏷ Show the Full List of 16 DOT(s)

References

1	ClinicalTrials.gov (NCT05226780) A Prospective, Long-Term, Interventional, Active Extension Study to Evaluate the Safety and Tolerability of NBI-921352 as Adjunctive Therapy in Subjects With SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE). U.S.National Institutes of Health.
2	ClinicalTrials.gov (NCT05818553) A Phase 2,Double-Blind,Randomized Clinical Trial to Explore the Safety,Tolerability,Efficacy, and Pharmacokinetics of PRAX-562 in Pediatric Participants With Developmental and Epileptic Encephalopathies Followed by Open-Label Extension(OLE). U.S.National Institutes of Health.
3	Epilepsy-causing sequence variations in SIK1 disrupt synaptic activity response gene expression and affect neuronal morphology.Eur J Hum Genet. 2017 Feb;25(2):216-221. doi: 10.1038/ejhg.2016.145. Epub 2016 Dec 14.
4	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.
5	A de novo KCNQ2 Gene Mutation Associated With Non-familial Early Onset Seizures: Case Report and Revision of Literature Data.Front Pediatr. 2019 Sep 6;7:348. doi: 10.3389/fped.2019.00348. eCollection 2019.
6	De novo KCNT1 mutations in early-onset epileptic encephalopathy.Epilepsia. 2015 Sep;56(9):e121-8. doi: 10.1111/epi.13072. Epub 2015 Jul 3.
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	MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation.Nat Genet. 2001 Nov;29(3):287-94. doi: 10.1038/ng762.
9	SCN1A gain of function in early infantile encephalopathy.Ann Neurol. 2019 Apr;85(4):514-525. doi: 10.1002/ana.25438. Epub 2019 Mar 7.
10	Ketogenic diet as a successful early treatment modality for SCN2A mutation.Brain Dev. 2019 Apr;41(4):389-391. doi: 10.1016/j.braindev.2018.10.015. Epub 2018 Nov 8.
11	Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy. Genet Med. 2016 Sep;18(9):898-905. doi: 10.1038/gim.2015.186. Epub 2016 Jan 21.
12	Clinical Phenotype of De Novo GNAO1 Mutation: Case Report and Review of Literature.Child Neurol Open. 2015 May 5;2(2):2329048X15583717. doi: 10.1177/2329048X15583717. eCollection 2015 Apr-Jun.
13	Mutations in the mitochondrial glutamate carrier SLC25A22 in neonatal epileptic encephalopathy with suppression bursts. Clin Genet. 2009 Aug;76(2):188-94. doi: 10.1111/j.1399-0004.2009.01236.x.
14	Hypospadias associated with hypertelorism, the mildest phenotype of Opitz syndrome.J Hum Genet. 2011 May;56(5):348-51. doi: 10.1038/jhg.2011.17. Epub 2011 Feb 17.
15	TopBP1 promotes malignant progression and correlates with poor prognosis in osteosarcoma.Eur Rev Med Pharmacol Sci. 2017 Sep;21(18):4022-4031.
16	Compound heterozygous BRAT1 mutations cause familial Ohtahara syndrome with hypertonia and microcephaly.J Hum Genet. 2014 Dec;59(12):687-90. doi: 10.1038/jhg.2014.91. Epub 2014 Oct 16.
17	Exosomal miR-675 from metastatic osteosarcoma promotes cell migration and invasion by targeting CALN1.Biochem Biophys Res Commun. 2018 Jun 2;500(2):170-176. doi: 10.1016/j.bbrc.2018.04.016. Epub 2018 Apr 11.
18	CASK aberrations in male patients with Ohtahara syndrome and cerebellar hypoplasia.Epilepsia. 2012 Aug;53(8):1441-9. doi: 10.1111/j.1528-1167.2012.03548.x. Epub 2012 Jun 18.
19	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.
20	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.
21	Heterogeneous expression and biological function of SOX18 in osteosaroma.J Cell Biochem. 2018 May;119(5):4184-4192. doi: 10.1002/jcb.26635. Epub 2018 Jan 22.
22	Titanium particles suppress expression of osteoblastic phenotype in human mesenchymal stem cells.J Orthop Res. 2002 Nov;20(6):1175-84. doi: 10.1016/S0736-0266(02)00076-1.
23	In vitro production of Spodoptera exigua multiple nucleopolyhedrovirus with enhanced insecticidal activity using a genotypically defined virus inoculum.J Biotechnol. 2017 Oct 10;259:19-25. doi: 10.1016/j.jbiotec.2017.08.001. Epub 2017 Aug 2.
24	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.
25	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.
26	Lentiviral Vector-Mediated SHC3 Silencing Exacerbates Oxidative Stress Injury in Nigral Dopamine Neurons by Regulating the PI3K-AKT-FoxO Signaling Pathway in Rats with Parkinson's Disease.Cell Physiol Biochem. 2018;49(3):971-984. doi: 10.1159/000493228. Epub 2018 Sep 5.
27	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.
28	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.