Details of Disease

Disease Name

Infantile epileptic-dyskinetic encephalopathy

Definition

Infantile epileptic-dyskinetic encephalopathy is a monogenic disease with epilepsy characterized by developmental delay and infantile spasms in the first months of life, followed by chorea and generalized dystonia and progressing to quadriplegic dyskinesia, recurrent status dystonicus, intractable focal epilepsy and severe intellectual disability.

Disease Hierarchy

DISD44TL: Combined dystonia

DISD2ZNC: Infantile epileptic-dyskinetic encephalopathy

Disease Identifiers

MONDO ID

MONDO_0018226

MESH ID

C567924

UMLS CUI

C4552072

MedGen ID

1637882

Orphanet ID

364063

SNOMED CT ID

771223000

General Information of Disease (ID: DISD2ZNC)

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	[1]
HCN1	TTNB6UQ	Disputed	Genetic Variation	[2]
KCNQ2	TTPXI3S	Strong	Genetic Variation	[3]
KCNT1	TTGJFK1	Strong	Genetic Variation	[4]
PLCB1	TTLPGU7	Strong	Genetic Variation	[5]
SCN1A	TTANOZH	Strong	Biomarker	[6]
SCN2A	TTLJTUF	Strong	Genetic Variation	[7]
SCN8A	TT54ERL	Strong	Biomarker	[8]
DNM1	TTE3JW9	Definitive	Biomarker	[9]
GNAO1	TTAXD8Z	Definitive	Biomarker	[10]
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⏷ 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	Genetic Variation	[11]
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This Disease Is Related to 26 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CAMK2G	OTHD9KJG	Limited	Biomarker	[12]
ARX	OTBGYH25	Supportive	X-linked	[13]
KLHL17	OTUWIJIQ	moderate	Genetic Variation	[14]
ATP1A3	OTM8EG6H	Strong	Biomarker	[15]
BRAT1	OT5ABVYX	Strong	Genetic Variation	[16]
BSCL2	OT73V6Y4	Strong	Genetic Variation	[17]
CASK	OT8EF7ZF	Strong	Genetic Variation	[18]
CCDC88A	OT3SSYYC	Strong	Biomarker	[19]
CDKL5	OTGL5HRV	Strong	Genetic Variation	[20]
CYFIP2	OTCAY35T	Strong	Biomarker	[21]
DMXL2	OTB4JWN3	Strong	Genetic Variation	[22]
HNRNPU	OTLQN1E2	Strong	Genetic Variation	[23]
KCNAB1	OT25GJE9	Strong	Genetic Variation	[24]
LIPT1	OT2KCI00	Strong	Biomarker	[25]
NECAP1	OTH49JRW	Strong	Genetic Variation	[26]
NEUROD2	OTJMMX9K	Strong	Genetic Variation	[27]
NSF	OTKRJ2ZT	Strong	Genetic Variation	[28]
PCDH19	OTSOW3MV	Strong	Biomarker	[29]
PIGP	OTGYAH4X	Strong	Genetic Variation	[30]
PIGQ	OTOD93DQ	Strong	Biomarker	[31]
SCN1B	OTGD78J3	Strong	Genetic Variation	[32]
SPTAN1	OT6VY3A3	Strong	Genetic Variation	[33]
SRGAP2	OTUWFMCQ	Strong	Genetic Variation	[34]
SRGAP3	OT9ZS72C	Strong	Genetic Variation	[34]
TBC1D24	OTKZUSMD	Strong	Genetic Variation	[35]
TRIO	OT71X1AK	Strong	Genetic Variation	[36]
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⏷ Show the Full List of 26 DOT(s)

References

1	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.
2	A novel de novo HCN1 loss-of-function mutation in genetic generalized epilepsy causing increased neuronal excitability.Neurobiol Dis. 2018 Oct;118:55-63. doi: 10.1016/j.nbd.2018.06.012. Epub 2018 Jun 21.
3	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.
4	Functional consequences of a KCNT1 variant associated with status dystonicus and early-onset infantile encephalopathy.Ann Clin Transl Neurol. 2019 Sep;6(9):1606-1615. doi: 10.1002/acn3.50847. Epub 2019 Jul 15.
5	Epilepsy is not a mandatory feature of STXBP1 associated ataxia-tremor-retardation syndrome.Eur J Paediatr Neurol. 2016 Jul;20(4):661-5. doi: 10.1016/j.ejpn.2016.04.005. Epub 2016 Apr 28.
6	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.
7	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.
8	Distinct functional alterations in SCN8A epilepsy mutant channels.J Physiol. 2020 Jan;598(2):381-401. doi: 10.1113/JP278952. Epub 2019 Dec 31.
9	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.
10	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.
11	Ohtahara syndrome with emphasis on recent genetic discovery.Brain Dev. 2012 Jun;34(6):459-68. doi: 10.1016/j.braindev.2011.09.004. Epub 2011 Oct 2.
12	Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies.PLoS One. 2017 Apr 7;12(4):e0174964. doi: 10.1371/journal.pone.0174964. eCollection 2017.
13	Expansion of the first PolyA tract of ARX causes infantile spasms and status dystonicus. Neurology. 2007 Jul 31;69(5):427-33. doi: 10.1212/01.wnl.0000266594.16202.c1.
14	Copy number variants and infantile spasms: evidence for abnormalities in ventral forebrain development and pathways of synaptic function.Eur J Hum Genet. 2011 Dec;19(12):1238-45. doi: 10.1038/ejhg.2011.121. Epub 2011 Jun 22.
15	Relapsing encephalopathy with cerebellar ataxia related to an ATP1A3 mutation.Dev Med Child Neurol. 2015 Dec;57(12):1183-6. doi: 10.1111/dmcn.12927. Epub 2015 Sep 23.
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	A de novo heterozygous missense BSCL2 variant in 2 siblings with intractable developmental and epileptic encephalopathy.Seizure. 2019 Oct;71:161-165. doi: 10.1016/j.seizure.2019.07.019. Epub 2019 Jul 25.
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	CCDC88A mutations cause PEHO-like syndrome in humans and mouse. Brain. 2016 Apr;139(Pt 4):1036-44. doi: 10.1093/brain/aww014. Epub 2016 Feb 25.
20	Clinical evolution and epilepsy outcome in three patients with CDKL5-related developmental encephalopathy.Epileptic Disord. 2019 Jun 1;21(3):271-277. doi: 10.1684/epd.2019.1071.
21	Neuronal function and dysfunction of CYFIP2: from actin dynamics to early infantile epileptic encephalopathy.BMB Rep. 2019 May;52(5):304-311. doi: 10.5483/BMBRep.2019.52.5.097.
22	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.
23	Clinical and molecular characterization of de novo loss of function variants in HNRNPU.Am J Med Genet A. 2017 Oct;173(10):2680-2689. doi: 10.1002/ajmg.a.38388. Epub 2017 Aug 16.
24	Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.PLoS One. 2015 Nov 6;10(11):e0141782. doi: 10.1371/journal.pone.0141782. eCollection 2015.
25	LIPT1 deficiency presenting as early infantile epileptic encephalopathy, Leigh disease, and secondary pyruvate dehydrogenase complex deficiency.Am J Med Genet A. 2018 May;176(5):1184-1189. doi: 10.1002/ajmg.a.38654.
26	A novel homozygous truncating variant of NECAP1 in early infantile epileptic encephalopathy: the second case report of EIEE21.J Hum Genet. 2019 Apr;64(4):347-350. doi: 10.1038/s10038-018-0556-2. Epub 2019 Jan 9.
27	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.
28	De novo NSF mutations cause early infantile epileptic encephalopathy. Ann Clin Transl Neurol. 2019 Nov;6(11):2334-2339. doi: 10.1002/acn3.50917. Epub 2019 Nov 1.
29	The Role of Protocadherin 19 (PCDH19) in Neurodevelopment and in the Pathophysiology of Early Infantile Epileptic Encephalopathy-9 (EIEE9).Dev Neurobiol. 2019 Jan;79(1):75-84. doi: 10.1002/dneu.22654. Epub 2019 Jan 18.
30	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.
31	PIGQ glycosylphosphatidylinositol-anchored protein deficiency: Characterizing the phenotype.Am J Med Genet A. 2019 Jul;179(7):1270-1275. doi: 10.1002/ajmg.a.61185. Epub 2019 May 30.
32	SCN1B-linked early infantile developmental and epileptic encephalopathy.Ann Clin Transl Neurol. 2019 Dec;6(12):2354-2367. doi: 10.1002/acn3.50921. Epub 2019 Nov 11.
33	Novel 9q34.11 gene deletions encompassing combinations of four Mendelian disease genes: STXBP1, SPTAN1, ENG, and TOR1A.Genet Med. 2012 Oct;14(10):868-76. doi: 10.1038/gim.2012.65. Epub 2012 Jun 21.
34	Early infantile epileptic encephalopathy associated with the disrupted gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2).Am J Med Genet A. 2012 Jan;158A(1):199-205. doi: 10.1002/ajmg.a.34363. Epub 2011 Nov 21.
35	The phenotypic landscape of a Tbc1d24 mutant mouse includes convulsive seizures resembling human early infantile epileptic encephalopathy.Hum Mol Genet. 2019 May 1;28(9):1530-1547. doi: 10.1093/hmg/ddy445.
36	A de novo SCN8A heterozygous mutation in a child with epileptic encephalopathy: a case report.BMC Pediatr. 2019 Nov 1;19(1):400. doi: 10.1186/s12887-019-1796-9.