Details of Disease

General Information of Disease (ID: DISISEI2)

Disease Name Undetermined early-onset epileptic encephalopathy
Synonyms undetermined early-onset epileptic encephalopathy; undetermined EOEE
Definition
A rare infantile epilepsy syndrome characterized by early onset of seizures of variable type and severity, potentially associated with a spectrum of clinical signs and symptoms including delay or lack of psychomotor development, intellectual disability, poor or absent speech development, behavioral abnormalities, hypotonia, movement disorders, spasticity, microcephaly, and dysmorphic facial features, among others. Brain imaging findings are also variable and may include cerebral atrophy or white matter abnormalities.
Disease Hierarchy
DISD715V: Hereditary neurological disease
DIS1BLHT: Inborn disorder of amino acid transport
DISTEZKR: Infantile epilepsy syndrome
DISH73EI: Neonatal epilepsy syndrome
DISISEI2: Undetermined early-onset epileptic encephalopathy
Disease Identifiers
MONDO ID
MONDO_0018614
UMLS CUI
C5680057
MedGen ID
1826068
Orphanet ID
442835

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 41 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
UBA5 OTJ322WE Supportive Autosomal dominant [1]
WWOX OTBDGSMG Supportive Autosomal dominant [2]
YWHAG OTYQTMPI Supportive Autosomal dominant [3]
ACTL6B OTO7EJIS Supportive Autosomal dominant [20]
AP3B2 OT7BFBLP Supportive Autosomal dominant [21]
ATP6V1A OTYZ2S9E Supportive Autosomal dominant [4]
CACNA1B OTRM0XDW Supportive Autosomal dominant [16]
CDK19 OTVMM0CP Supportive Autosomal dominant [5]
CELF2 OTLJJ4VT Supportive Autosomal dominant [22]
CLTC OTBFASMA Supportive Autosomal dominant [8]
CNKSR2 OTAGERJ2 Supportive Autosomal dominant [23]
CYFIP2 OTCAY35T Supportive Autosomal dominant [24]
DALRD3 OTU79VIP Supportive Autosomal dominant [25]
DHDDS OTVLYBUS Supportive Autosomal dominant [8]
DNM1 OTI8X2WQ Supportive Autosomal dominant [26]
EEF1A2 OT9Z23K5 Supportive Autosomal dominant [27]
FGF12 OTBM9QIO Supportive Autosomal dominant [28]
FGF13 OTHNNVSG Supportive Autosomal dominant [29]
GABRA2 OT9TZ2E0 Supportive Autosomal dominant [6]
GABRA5 OTBIKWQT Supportive Autosomal dominant [7]
GABRB2 OTAOZIGX Supportive Autosomal dominant [8]
GABRG2 OTGNDWUO Supportive Autosomal dominant [9]
GRIN2D OTTEKYKQ Supportive Autosomal dominant [10]
HCN1 OTVOWKQ7 Supportive Autosomal dominant [11]
KCNB1 OTLCU4FR Supportive Autosomal dominant [12]
NECAP1 OTH49JRW Supportive Autosomal dominant [30]
NTRK2 OTD557PU Supportive Autosomal dominant [8]
NUS1 OT4DQ82L Supportive Autosomal dominant [8]
PARS2 OTMBBH7K Supportive Autosomal dominant [31]
PPP3CA OT58PUEN Supportive Autosomal dominant [13]
SCN3A OT4C2LCB Supportive Autosomal dominant [14]
SCN8A OT0JGIZN Supportive Autosomal dominant [17]
SLC13A5 OTPH1TA7 Supportive Autosomal dominant [18]
SLC1A2 OTEP3QGN Supportive Autosomal dominant [19]
STXBP1 OTRYA8C3 Supportive Autosomal dominant [32]
SYNJ1 OTTE02XC Supportive Autosomal dominant [33]
SZT2 OTB4FVP4 Supportive Autosomal dominant [34]
TRAK1 OTMQVYNP Supportive Autosomal dominant [35]
KCNA2 OT18SUP8 Strong Autosomal dominant [15]
AARS1 OTW8D813 Definitive Autosomal recessive [36]
CACNA1A OTY08SIX Definitive Autosomal dominant [19]
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⏷ Show the Full List of 41 DOT(s)
This Disease Is Related to 13 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
ATP6V1A TTL2PXZ Supportive Autosomal dominant [4]
CDK19 TTNABU9 Supportive Autosomal dominant [5]
GABRA2 TTBMV1G Supportive Autosomal dominant [6]
GABRA5 TTNZPQ1 Supportive Autosomal dominant [7]
GABRB2 TTZA1NY Supportive Autosomal dominant [8]
GABRG2 TT06RH5 Supportive Autosomal dominant [9]
GRIN2D TT5POTG Supportive Autosomal dominant [10]
HCN1 TTNB6UQ Supportive Autosomal dominant [11]
KCNB1 TT5OEKU Supportive Autosomal dominant [12]
NTRK2 TTKN7QR Supportive Autosomal dominant [8]
PPP3CA TTA4LDE Supportive Autosomal dominant [13]
SCN3A TTAXZ0K Supportive Autosomal dominant [14]
KCNA2 TTVFB0O Strong Autosomal dominant [15]
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⏷ Show the Full List of 13 DTT(s)
This Disease Is Related to 5 DTP Molecule(s)
Gene Name DTP ID Evidence Level Mode of Inheritance REF
CACNA1B DTMKD76 Supportive Autosomal dominant [16]
SCN8A DTIMSBJ Supportive Autosomal dominant [17]
SLC13A5 DTFPWJ9 Supportive Autosomal dominant [18]
SLC1A2 DT0VAI5 Supportive Autosomal dominant [19]
CACNA1A DTYKGPB Definitive Autosomal dominant [19]
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References

1 Biallelic Variants in UBA5 Link Dysfunctional UFM1?Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy. Am J Hum Genet. 2016 Sep 1;99(3):683-694. doi: 10.1016/j.ajhg.2016.06.020. Epub 2016 Aug 18.
2 WWOX-related encephalopathies: delineation of the phenotypical spectrum and emerging genotype-phenotype correlation. J Med Genet. 2015 Jan;52(1):61-70. doi: 10.1136/jmedgenet-2014-102748. Epub 2014 Nov 19.
3 De Novo Mutations in YWHAG Cause Early-Onset Epilepsy. Am J Hum Genet. 2017 Aug 3;101(2):300-310. doi: 10.1016/j.ajhg.2017.07.004.
4 De novo mutations of the ATP6V1A gene cause developmental encephalopathy with epilepsy. Brain. 2018 Jun 1;141(6):1703-1718. doi: 10.1093/brain/awy092.
5 De Novo Variants in CDK19 Are Associated with a Syndrome Involving Intellectual Disability and Epileptic Encephalopathy. Am J Hum Genet. 2020 May 7;106(5):717-725. doi: 10.1016/j.ajhg.2020.04.001. Epub 2020 Apr 23.
6 Novel GABRA2 variants in epileptic encephalopathy and intellectual disability with seizures. Brain. 2019 May 1;142(5):e15. doi: 10.1093/brain/awz079.
7 Altered inhibitory synapses in de novo GABRA5 and GABRA1 mutations associated with early onset epileptic encephalopathies. Brain. 2019 Jul 1;142(7):1938-1954. doi: 10.1093/brain/awz123.
8 High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies. Am J Hum Genet. 2017 Nov 2;101(5):664-685. doi: 10.1016/j.ajhg.2017.09.008.
9 De novo GABRG2 mutations associated with epileptic encephalopathies. Brain. 2017 Jan;140(1):49-67. doi: 10.1093/brain/aww272. Epub 2016 Nov 17.
10 GRIN2D Recurrent De Novo Dominant Mutation Causes a Severe Epileptic Encephalopathy Treatable with NMDA Receptor Channel Blockers. Am J Hum Genet. 2016 Oct 6;99(4):802-816. doi: 10.1016/j.ajhg.2016.07.013. Epub 2016 Sep 8.
11 De novo mutations in HCN1 cause early infantile epileptic encephalopathy. Nat Genet. 2014 Jun;46(6):640-5. doi: 10.1038/ng.2952. Epub 2014 Apr 20.
12 De novo KCNB1 mutations in epileptic encephalopathy. Ann Neurol. 2014 Oct;76(4):529-540. doi: 10.1002/ana.24263. Epub 2014 Sep 19.
13 De Novo Mutations in PPP3CA Cause Severe Neurodevelopmental Disease with Seizures. Am J Hum Genet. 2017 Oct 5;101(4):516-524. doi: 10.1016/j.ajhg.2017.08.013. Epub 2017 Sep 21.
14 Mutations in SCN3A cause early infantile epileptic encephalopathy. Ann Neurol. 2018 Apr;83(4):703-717. doi: 10.1002/ana.25188. Epub 2018 Mar 30.
15 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.
16 Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia. Am J Hum Genet. 2019 May 2;104(5):948-956. doi: 10.1016/j.ajhg.2019.03.005. Epub 2019 Apr 11.
17 De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP. Am J Hum Genet. 2012 Mar 9;90(3):502-10. doi: 10.1016/j.ajhg.2012.01.006. Epub 2012 Feb 23.
18 Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy with seizure onset in the first days of life. Am J Hum Genet. 2014 Jul 3;95(1):113-20. doi: 10.1016/j.ajhg.2014.06.006.
19 De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies. Am J Hum Genet. 2016 Aug 4;99(2):287-98. doi: 10.1016/j.ajhg.2016.06.003. Epub 2016 Jul 28.
20 Mutations in ACTL6B Cause Neurodevelopmental Deficits and Epilepsy and Lead to Loss of Dendrites in Human Neurons. Am J Hum Genet. 2019 May 2;104(5):815-834. doi: 10.1016/j.ajhg.2019.03.022. Epub 2019 Apr 25.
21 Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy. Am J Hum Genet. 2016 Dec 1;99(6):1368-1376. doi: 10.1016/j.ajhg.2016.10.009. Epub 2016 Nov 23.
22 De novo variants in CELF2 that disrupt the nuclear localization signal cause developmental and epileptic encephalopathy. Hum Mutat. 2021 Jan;42(1):66-76. doi: 10.1002/humu.24130. Epub 2020 Nov 10.
23 Absent CNKSR2 causes seizures and intellectual, attention, and language deficits. Ann Neurol. 2014 Nov;76(5):758-64. doi: 10.1002/ana.24274. Epub 2014 Oct 4.
24 De novo hotspot variants in CYFIP2 cause early-onset epileptic encephalopathy. Ann Neurol. 2018 Apr;83(4):794-806. doi: 10.1002/ana.25208.
25 DALRD3 encodes a protein mutated in epileptic encephalopathy that targets arginine tRNAs for 3-methylcytosine modification. Nat Commun. 2020 May 19;11(1):2510. doi: 10.1038/s41467-020-16321-6.
26 De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies. Am J Hum Genet. 2014 Oct 2;95(4):360-70. doi: 10.1016/j.ajhg.2014.08.013. Epub 2014 Sep 25.
27 Exome sequencing reveals new causal mutations in children with epileptic encephalopathies. Epilepsia. 2013 Jul;54(7):1270-81. doi: 10.1111/epi.12201. Epub 2013 May 3.
28 Gain-of-function FHF1 mutation causes early-onset epileptic encephalopathy with cerebellar atrophy. Neurology. 2016 Jun 7;86(23):2162-70. doi: 10.1212/WNL.0000000000002752. Epub 2016 May 4.
29 Missense variants in the N-terminal domain of the A isoform of FHF2/FGF13 cause an X-linked developmental and epileptic encephalopathy. Am J Hum Genet. 2021 Jan 7;108(1):176-185. doi: 10.1016/j.ajhg.2020.10.017. Epub 2020 Nov 26.
30 NECAP1 loss of function leads to a severe infantile epileptic encephalopathy. J Med Genet. 2014 Apr;51(4):224-8. doi: 10.1136/jmedgenet-2013-102030. Epub 2014 Jan 7.
31 The genotypic and phenotypic spectrum of PARS2-related infantile-onset encephalopathy. J Hum Genet. 2018 Sep;63(9):971-980. doi: 10.1038/s10038-018-0478-z. Epub 2018 Jun 18.
32 STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy. Neurology. 2016 Mar 8;86(10):954-62. doi: 10.1212/WNL.0000000000002457. Epub 2016 Feb 10.
33 Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline. Brain. 2016 Sep;139(Pt 9):2420-30. doi: 10.1093/brain/aww180. Epub 2016 Jul 19.
34 Biallelic SZT2 mutations cause infantile encephalopathy with epilepsy and dysmorphic corpus callosum. Am J Hum Genet. 2013 Sep 5;93(3):524-9. doi: 10.1016/j.ajhg.2013.07.005. Epub 2013 Aug 8.
35 Deleterious variants in TRAK1 disrupt mitochondrial movement and cause fatal encephalopathy. Brain. 2017 Mar 1;140(3):568-581. doi: 10.1093/brain/awx002.
36 Deficient activity of alanyl-tRNA synthetase underlies an autosomal recessive syndrome of progressive microcephaly, hypomyelination, and epileptic encephalopathy. Hum Mutat. 2017 Oct;38(10):1348-1354. doi: 10.1002/humu.23250. Epub 2017 Jun 23.