DEE28
MCID: DVL054
MIFTS: 32

Developmental and Epileptic Encephalopathy 28 (DEE28)

Categories: Cancer diseases, Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Liver diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Developmental and Epileptic Encephalopathy 28

MalaCards integrated aliases for Developmental and Epileptic Encephalopathy 28:

Name: Developmental and Epileptic Encephalopathy 28 57 12
Epileptic Encephalopathy, Early Infantile, 28 57 73 29 6
Early Infantile Epileptic Encephalopathy 28 12 15
Eiee28 57 73
Dee28 57 12
Epileptic Encephalopathy, Early Infantile, 28; Eiee28 57
Encephalopathy, Epileptic, Early Infantile, Type 28 39

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset in first months of life
premature death may occur


HPO:

31
developmental and epileptic encephalopathy 28:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:



Summaries for Developmental and Epileptic Encephalopathy 28

OMIM® : 57 Developmental and epileptic encephalopathy-28 (DEE28) is an autosomal recessive severe neurologic disorder characterized by the onset of refractory seizures in the first months of life. Affected individuals have severe axial hypotonia and profoundly impaired psychomotor development. More severely affected patients have acquired microcephaly, poor or absent visual contact, and retinal degeneration; early death may occur (summary by Mignot et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. (616211) (Updated 05-Mar-2021)

MalaCards based summary : Developmental and Epileptic Encephalopathy 28, also known as epileptic encephalopathy, early infantile, 28, is related to colon small cell carcinoma, and has symptoms including muscle rigidity and muscle spasticity. An important gene associated with Developmental and Epileptic Encephalopathy 28 is WWOX (WW Domain Containing Oxidoreductase). Related phenotypes are optic atrophy and abnormal electroretinogram

Disease Ontology : 12 A developmental and epileptic encephalopathy characterized by onset in the first months of life of refractory seizures, severe axial hypotonia, and profoundly impaired psychomotor development that has material basis in homozygous or compound heterozygous mutation in the WWOX gene on chromosome 16q23.

UniProtKB/Swiss-Prot : 73 Epileptic encephalopathy, early infantile, 28: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent.

Related Diseases for Developmental and Epileptic Encephalopathy 28

Diseases in the Developmental and Epileptic Encephalopathy family:

Developmental and Epileptic Encephalopathy 9 Developmental and Epileptic Encephalopathy 8
Developmental and Epileptic Encephalopathy 2 Developmental and Epileptic Encephalopathy 36
Developmental and Epileptic Encephalopathy 90 Developmental and Epileptic Encephalopathy 1
Developmental and Epileptic Encephalopathy 3 Developmental and Epileptic Encephalopathy 4
Developmental and Epileptic Encephalopathy 39 Developmental and Epileptic Encephalopathy 5
Developmental and Epileptic Encephalopathy 7 Developmental and Epileptic Encephalopathy 11
Developmental and Epileptic Encephalopathy 12 Developmental and Epileptic Encephalopathy 13
Developmental and Epileptic Encephalopathy 14 Developmental and Epileptic Encephalopathy 15
Developmental and Epileptic Encephalopathy 16 Developmental and Epileptic Encephalopathy 17
Developmental and Epileptic Encephalopathy 18 Developmental and Epileptic Encephalopathy 19
Developmental and Epileptic Encephalopathy 21 Developmental and Epileptic Encephalopathy 23
Developmental and Epileptic Encephalopathy 24 Developmental and Epileptic Encephalopathy 26
Developmental and Epileptic Encephalopathy 27 Developmental and Epileptic Encephalopathy 28
Developmental and Epileptic Encephalopathy 29 Developmental and Epileptic Encephalopathy 30
Developmental and Epileptic Encephalopathy 31 Developmental and Epileptic Encephalopathy 32
Developmental and Epileptic Encephalopathy 33 Developmental and Epileptic Encephalopathy 50
Developmental and Epileptic Encephalopathy 34 Developmental and Epileptic Encephalopathy 35
Developmental and Epileptic Encephalopathy 37 Developmental and Epileptic Encephalopathy 38
Developmental and Epileptic Encephalopathy 40 Developmental and Epileptic Encephalopathy 41
Developmental and Epileptic Encephalopathy 42 Developmental and Epileptic Encephalopathy 43
Developmental and Epileptic Encephalopathy 44 Developmental and Epileptic Encephalopathy 45
Developmental and Epileptic Encephalopathy 46 Developmental and Epileptic Encephalopathy 47
Developmental and Epileptic Encephalopathy 48 Developmental and Epileptic Encephalopathy 49
Developmental and Epileptic Encephalopathy 51 Developmental and Epileptic Encephalopathy 52
Developmental and Epileptic Encephalopathy 53 Developmental and Epileptic Encephalopathy 54
Developmental and Epileptic Encephalopathy 55 Developmental and Epileptic Encephalopathy 56
Developmental and Epileptic Encephalopathy 57 Developmental and Epileptic Encephalopathy 58
Developmental and Epileptic Encephalopathy 59 Developmental and Epileptic Encephalopathy 60
Developmental and Epileptic Encephalopathy 61 Developmental and Epileptic Encephalopathy 62
Developmental and Epileptic Encephalopathy 63 Developmental and Epileptic Encephalopathy 64
Developmental and Epileptic Encephalopathy 65 Developmental and Epileptic Encephalopathy 66
Developmental and Epileptic Encephalopathy 67 Developmental and Epileptic Encephalopathy 68
Developmental and Epileptic Encephalopathy 69 Developmental and Epileptic Encephalopathy 70
Developmental and Epileptic Encephalopathy 71 Developmental and Epileptic Encephalopathy 72
Developmental and Epileptic Encephalopathy 73 Developmental and Epileptic Encephalopathy 74
Developmental and Epileptic Encephalopathy 75 Developmental and Epileptic Encephalopathy 76
Developmental and Epileptic Encephalopathy 78 Developmental and Epileptic Encephalopathy 79
Developmental and Epileptic Encephalopathy 80 Developmental and Epileptic Encephalopathy 81
Developmental and Epileptic Encephalopathy 82 Developmental and Epileptic Encephalopathy 83
Developmental and Epileptic Encephalopathy 84 Developmental and Epileptic Encephalopathy 86
Developmental and Epileptic Encephalopathy 87 Developmental and Epileptic Encephalopathy 88
Developmental and Epileptic Encephalopathy 89

Diseases related to Developmental and Epileptic Encephalopathy 28 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 colon small cell carcinoma 9.4 MSI2 GBX2

Symptoms & Phenotypes for Developmental and Epileptic Encephalopathy 28

Human phenotypes related to Developmental and Epileptic Encephalopathy 28:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 optic atrophy 31 occasional (7.5%) HP:0000648
2 abnormal electroretinogram 31 occasional (7.5%) HP:0000512
3 hypoplasia of the corpus callosum 31 occasional (7.5%) HP:0002079
4 cerebral atrophy 31 occasional (7.5%) HP:0002059
5 retinal degeneration 31 occasional (7.5%) HP:0000546
6 delayed myelination 31 occasional (7.5%) HP:0012448
7 spasticity 31 HP:0001257
8 hyperreflexia 31 HP:0001347
9 global developmental delay 31 HP:0001263
10 rigidity 31 HP:0002063
11 muscular hypotonia of the trunk 31 HP:0008936
12 hypokinesia 31 HP:0002375
13 epileptic encephalopathy 31 HP:0200134
14 progressive microcephaly 31 HP:0000253
15 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Central Nervous System:
spasticity
hyperreflexia
rigidity
hypokinesia
epileptic encephalopathy
more
Muscle Soft Tissue:
axial hypotonia

Head And Neck Eyes:
optic atrophy (in some patients)
retinal degeneration (in some patients)
poor or lack of visual contact (in some patients)
abnormal electroretinogram (in some patients)

Head And Neck Head:
microcephaly, progressive (in some patients)

Clinical features from OMIM®:

616211 (Updated 05-Mar-2021)

UMLS symptoms related to Developmental and Epileptic Encephalopathy 28:


muscle rigidity, muscle spasticity

GenomeRNAi Phenotypes related to Developmental and Epileptic Encephalopathy 28 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.1 SOX21 WWOX
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.1 LAMA5 SOX21 WWOX
3 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-3 9.1 SOX21

Drugs & Therapeutics for Developmental and Epileptic Encephalopathy 28

Search Clinical Trials , NIH Clinical Center for Developmental and Epileptic Encephalopathy 28

Genetic Tests for Developmental and Epileptic Encephalopathy 28

Genetic tests related to Developmental and Epileptic Encephalopathy 28:

# Genetic test Affiliating Genes
1 Epileptic Encephalopathy, Early Infantile, 28 29 WWOX

Anatomical Context for Developmental and Epileptic Encephalopathy 28

Publications for Developmental and Epileptic Encephalopathy 28

Articles related to Developmental and Epileptic Encephalopathy 28:

# Title Authors PMID Year
1
WWOX-related encephalopathies: delineation of the phenotypical spectrum and emerging genotype-phenotype correlation. 57 6
25411445 2015
2
The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration. 6 57
24456803 2014
3
A spontaneous mutation of the Wwox gene and audiogenic seizures in rats with lethal dwarfism and epilepsy. 57
19500159 2009
4
WWOX Loss of Function in Neurodevelopmental and Neurodegenerative Disorders. 61
33255508 2020
5
Wwox deletion leads to reduced GABA-ergic inhibitory interneuron numbers and activation of microglia and astrocytes in mouse hippocampus. 61
30290271 2019

Variations for Developmental and Epileptic Encephalopathy 28

ClinVar genetic disease variations for Developmental and Epileptic Encephalopathy 28:

6 (show all 36)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 WWOX NM_016373.4(WWOX):c.160C>T (p.Arg54Ter) SNV Pathogenic 120325 rs587777248 16:78142372-78142372 16:78108475-78108475
2 WWOX NM_016373.3(WWOX):c.-366-?_516+?del Deletion Pathogenic 180246 16:78133327-78198186 16:78099413-78164289
3 WWOX NM_016373.3(WWOX):c.517-?_605+?del Deletion Pathogenic 180247 16:78420757-78420845 16:78342602-78424602
4 WWOX-AS1 NM_016373.2(WWOX):c.517-?_605+?del Deletion Pathogenic 180248 16:78260521-78417344 16:78226624-78383447
5 WWOX NM_016373.4(WWOX):c.46_49del (p.Asp16fs) Deletion Pathogenic 180250 rs730880291 16:78133720-78133723 16:78099823-78099826
6 WWOX GRCh37/hg19 16q23.1(chr16:78143268-78154701) copy number loss Pathogenic 625675 16:78143268-78154701
7 WWOX GRCh37/hg19 16q23.1(chr16:78409180-78431277) copy number loss Pathogenic 625676 16:78409180-78431277
8 WWOX GRCh37/hg19 16q23.1(chr16:78458774-78463512) copy number loss Pathogenic 625820 16:78458774-78463512
9 WWOX NM_016373.4(WWOX):c.107+1G>A SNV Pathogenic 689796 rs1300924648 16:78133783-78133783 16:78099886-78099886
10 WWOX GRCh37/hg19 16q23.1(chr16:78458767-78458953) copy number loss Pathogenic 915975 16:78458767-78458953
11 WWOX NM_016373.4(WWOX):c.184G>T (p.Gly62Ter) SNV Pathogenic 976436 16:78143686-78143686 16:78109789-78109789
12 WWOX Deletion Pathogenic 978033 16:78152047-78188346
13 WWOX NM_016373.4(WWOX):c.790C>T (p.Arg264Ter) SNV Pathogenic 241105 rs756762196 16:78458951-78458951 16:78425054-78425054
14 WWOX NM_016373.4(WWOX):c.1005G>A (p.Trp335Ter) SNV Pathogenic 180249 rs730880290 16:78466598-78466598 16:78432701-78432701
15 WWOX NM_016373.4(WWOX):c.140C>G (p.Pro47Arg) SNV Pathogenic 180251 rs730880292 16:78142352-78142352 16:78108455-78108455
16 WWOX NM_016373.4(WWOX):c.689A>C (p.Gln230Pro) SNV Pathogenic/Likely pathogenic 813767 16:78458850-78458850 16:78424953-78424953
17 WWOX GRCh37/hg19 16q23.1(chr16:78198080-78198186) copy number loss Likely pathogenic 813331 16:78198080-78198186
18 WWOX NM_016373.4(WWOX):c.918del (p.Glu306fs) Deletion Likely pathogenic 373950 rs1057518795 16:78466511-78466511 16:78432614-78432614
19 WWOX NM_016373.4(WWOX):c.183C>A (p.Tyr61Ter) SNV Likely pathogenic 373951 rs759766243 16:78143685-78143685 16:78109788-78109788
20 WWOX NM_016373.4(WWOX):c.606-1G>A SNV Likely pathogenic 183303 rs730882215 16:78458766-78458766 16:78424869-78424869
21 WWOX NM_016373.4(WWOX):c.791+1G>A SNV Likely pathogenic 495112 rs1164465811 16:78458953-78458953 16:78425056-78425056
22 WWOX NM_016373.4(WWOX):c.107+2_107+5del Deletion Likely pathogenic 493191 rs1555532979 16:78133784-78133787 16:78099884-78099887
23 WWOX NM_016373.4(WWOX):c.108-2A>T SNV Likely pathogenic 804478 rs1597207802 16:78142318-78142318 16:78108421-78108421
24 WWOX NM_016373.4(WWOX):c.990C>G (p.Asn330Lys) SNV Uncertain significance 433131 rs117209694 16:78466583-78466583 16:78432686-78432686
25 WWOX NM_016373.4(WWOX):c.341T>C (p.Met114Thr) SNV Uncertain significance 546463 rs761906386 16:78148983-78148983 16:78115086-78115086
26 WWOX NM_016373.4(WWOX):c.562C>A (p.Arg188Ser) SNV Uncertain significance 410086 rs199511589 16:78420802-78420802 16:78386905-78386905
27 WWOX NM_016373.4(WWOX):c.935C>A (p.Ser312Tyr) SNV Uncertain significance 578011 rs79399971 16:78466528-78466528 16:78432631-78432631
28 WWOX NM_016373.4(WWOX):c.1039C>A (p.Pro347Thr) SNV Uncertain significance 569507 rs200699154 16:78466632-78466632 16:78432735-78432735
29 WWOX NM_016373.4(WWOX):c.517-108243C>T SNV Uncertain significance 626053 rs551189075 16:78312514-78312514 16:78278617-78278617
30 WWOX NM_016373.4(WWOX):c.517C>T (p.His173Tyr) SNV Uncertain significance 931133 16:78420757-78420757 16:78386860-78386860
31 WWOX NM_016373.4(WWOX):c.16T>C (p.Tyr6His) SNV Uncertain significance 931445 16:78133691-78133691 16:78099794-78099794
32 WWOX NM_016373.4(WWOX):c.410G>T (p.Gly137Val) SNV Uncertain significance 635056 rs761879076 16:78198080-78198080 16:78164183-78164183
33 WWOX NM_016373.4(WWOX):c.791+18A>T SNV Uncertain significance 931770 16:78458970-78458970 16:78425073-78425073
34 WWOX NM_016373.4(WWOX):c.716T>G (p.Leu239Arg) SNV Uncertain significance 871669 16:78458877-78458877 16:78424980-78424980
35 WWOX NM_016373.4(WWOX):c.605+5G>A SNV Uncertain significance 450592 rs1039151413 16:78420850-78420850 16:78386953-78386953
36 NCF2 NM_000433.3(NCF2):c.1256A>T (p.Asn419Ile) SNV Benign 281211 rs35012521 1:183532364-183532364 1:183563229-183563229

UniProtKB/Swiss-Prot genetic disease variations for Developmental and Epileptic Encephalopathy 28:

73
# Symbol AA change Variation ID SNP ID
1 WWOX p.Pro47Arg VAR_072351 rs730880292

Expression for Developmental and Epileptic Encephalopathy 28

Search GEO for disease gene expression data for Developmental and Epileptic Encephalopathy 28.

Pathways for Developmental and Epileptic Encephalopathy 28

GO Terms for Developmental and Epileptic Encephalopathy 28

Biological processes related to Developmental and Epileptic Encephalopathy 28 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lung development GO:0030324 9.26 LOXL3 LAMA5
2 neural crest cell migration GO:0001755 9.16 LAMA5 GBX2
3 hair follicle development GO:0001942 8.96 SOX21 LAMA5
4 stem cell differentiation GO:0048863 8.62 SOX21 GPM6A

Sources for Developmental and Epileptic Encephalopathy 28

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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