DEE75
MCID: DVL099
MIFTS: 27

Developmental and Epileptic Encephalopathy 75 (DEE75)

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 75

MalaCards integrated aliases for Developmental and Epileptic Encephalopathy 75:

Name: Developmental and Epileptic Encephalopathy 75 57 12
Developmental and Epileptic Encephalopathy, 75 29 6
Epileptic Encephalopathy, Early Infantile, 75 57 72
Eiee75 57 72
Dee75 57 12
Epileptic Encephalopathy, Early Infantile, 75; Eiee75 57
Early Infantile Epileptic Encephalopathy 75 12

Characteristics:

OMIM®:

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

Miscellaneous:
early death may occur
onset in first months of life


HPO:

31
developmental and epileptic encephalopathy 75:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Developmental and Epileptic Encephalopathy 75

OMIM® : 57 Developmental and epileptic encephalopathy-75 (DEE75) is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by onset of severe refractory seizures in the first months of life. Patients often have global developmental delay before the onset of seizures, and thereafter achieve few milestones. EEG usually shows multifocal spikes and hypsarrhythmia, consistent with a clinical diagnosis of West syndrome. They have severely impaired intellectual development with inability to walk, absent speech, and hypotonia with axial hyperreflexia. Brain imaging shows progressive cerebral atrophy, frontal lobe atrophy, white matter abnormalities, and delayed myelination. Since the disorder is due to mitochondrial dysfunction, some patients may develop other organ involvement, including cardiomyopathy or liver and renal dysfunction. Death may occur in childhood (summary by Yin et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. (618437) (Updated 05-Apr-2021)

MalaCards based summary : Developmental and Epileptic Encephalopathy 75, is also known as developmental and epileptic encephalopathy, 75. An important gene associated with Developmental and Epileptic Encephalopathy 75 is PARS2 (Prolyl-TRNA Synthetase 2, Mitochondrial). Affiliated tissues include liver and cerebellum, and related phenotypes are global developmental delay and feeding difficulties in infancy

Disease Ontology : 12 A developmental and epileptic encephalopathy characterized by onset in the first months of life of severe refractory seizures, multifocal spikes and hypsarrhythmia on EEG, severely impaired intellectual development with inability to walk, absent speech, and hypotonia with axial hyperreflexia that has material basis in homozygous or compound heterozygous mutation in PARS2 on chromosome 1p32.3.

UniProtKB/Swiss-Prot : 72 Epileptic encephalopathy, early infantile, 75: A form of epileptic encephalopathy, a heterogeneous group of severe early-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. EIEE75 is an autosomal recessive form characterized by onset of severe refractory seizures in the first months of life.

Related Diseases for Developmental and Epileptic Encephalopathy 75

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 91 Developmental and Epileptic Encephalopathy 57
Developmental and Epileptic Encephalopathy 92 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 93
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

Symptoms & Phenotypes for Developmental and Epileptic Encephalopathy 75

Human phenotypes related to Developmental and Epileptic Encephalopathy 75:

31 (showing 31, show less)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 very rare (1%) HP:0001263
2 feeding difficulties in infancy 31 very rare (1%) HP:0008872
3 absent speech 31 very rare (1%) HP:0001344
4 prolonged neonatal jaundice 31 very rare (1%) HP:0006579
5 cardiomyopathy 31 very rare (1%) HP:0001638
6 postnatal microcephaly 31 very rare (1%) HP:0005484
7 hypsarrhythmia 31 very rare (1%) HP:0002521
8 decreased liver function 31 very rare (1%) HP:0001410
9 seizure 31 very rare (1%) HP:0001250
10 spasticity 31 HP:0001257
11 hyperreflexia 31 HP:0001347
12 hypertelorism 31 HP:0000316
13 wide nasal bridge 31 HP:0000431
14 short nose 31 HP:0003196
15 anteverted nares 31 HP:0000463
16 optic atrophy 31 HP:0000648
17 open mouth 31 HP:0000194
18 upslanted palpebral fissure 31 HP:0000582
19 proptosis 31 HP:0000520
20 short philtrum 31 HP:0000322
21 profound global developmental delay 31 HP:0012736
22 babinski sign 31 HP:0003487
23 sloping forehead 31 HP:0000340
24 hypoplasia of the corpus callosum 31 HP:0002079
25 optic disc pallor 31 HP:0000543
26 frontal cortical atrophy 31 HP:0006913
27 muscular hypotonia of the trunk 31 HP:0008936
28 cerebral visual impairment 31 HP:0100704
29 short chin 31 HP:0000331
30 epileptic encephalopathy 31 HP:0200134
31 cns hypomyelination 31 HP:0003429

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
spasticity
hyperreflexia
absent speech
cerebral atrophy
frontal cortical atrophy
more
Head And Neck Eyes:
optic atrophy
pale optic disks
cortical visual impairment

Head And Neck Face:
sloping forehead
dysmorphic features (in some patients)

Growth Other:
poor overall growth

Abdomen Liver:
liver dysfunction (in some patients)

Genitourinary Kidneys:
renal dysfunction (in some patients)

Laboratory Abnormalities:
serum or csf lactate may be increased, but may be normal

Head And Neck Nose:
anteverted nares
broad nasal bridge

Head And Neck Mouth:
open mouth

Abdomen Gastrointestinal:
poor feeding

Muscle Soft Tissue:
axial hypotonia

Cardiovascular Heart:
cardiomyopathy (in some patients)

Head And Neck Head:
microcephaly (down to -6 sd)

Clinical features from OMIM®:

618437 (Updated 05-Apr-2021)

Drugs & Therapeutics for Developmental and Epileptic Encephalopathy 75

Search Clinical Trials , NIH Clinical Center for Developmental and Epileptic Encephalopathy 75

Genetic Tests for Developmental and Epileptic Encephalopathy 75

Genetic tests related to Developmental and Epileptic Encephalopathy 75:

# Genetic test Affiliating Genes
1 Developmental and Epileptic Encephalopathy, 75 29 PARS2

Anatomical Context for Developmental and Epileptic Encephalopathy 75

MalaCards organs/tissues related to Developmental and Epileptic Encephalopathy 75:

40
Liver, Cerebellum

Publications for Developmental and Epileptic Encephalopathy 75

Articles related to Developmental and Epileptic Encephalopathy 75:

(showing 6, show less)
# Title Authors PMID Year
1
The genotypic and phenotypic spectrum of PARS2-related infantile-onset encephalopathy. 6 57
29915213 2018
2
Clinical and molecular characteristics of newly reported mitochondrial disease entity caused by biallelic PARS2 mutations. 6 57
29410512 2018
3
PARS2 and NARS2 mutations in infantile-onset neurodegenerative disorder. 57 6
28077841 2017
4
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre. 6 57
27290639 2016
5
Whole exome sequencing reveals mutations in NARS2 and PARS2, encoding the mitochondrial asparaginyl-tRNA synthetase and prolyl-tRNA synthetase, in patients with Alpers syndrome. 57 6
25629079 2015
6
Phenotypic and genotypic variability in Alpers syndrome. 6 57
22237560 2012

Variations for Developmental and Epileptic Encephalopathy 75

ClinVar genetic disease variations for Developmental and Epileptic Encephalopathy 75:

6 (showing 9, show less)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PARS2 NM_152268.4(PARS2):c.1130dup (p.Pro377_Lys378insTer) Duplication Pathogenic 183148 rs730882152 GRCh37: 1:55223704-55223705
GRCh38: 1:54758031-54758032
2 PARS2 NM_152268.4(PARS2):c.283G>A (p.Val95Ile) SNV Conflicting interpretations of pathogenicity 432121 rs147227819 GRCh37: 1:55224552-55224552
GRCh38: 1:54758879-54758879
3 PARS2 NM_152268.4(PARS2):c.604C>G (p.Arg202Gly) SNV Uncertain significance 632570 rs141760650 GRCh37: 1:55224231-55224231
GRCh38: 1:54758558-54758558
4 PARS2 NM_152268.4(PARS2):c.836C>T (p.Ser279Leu) SNV Uncertain significance 183149 rs730882153 GRCh37: 1:55223999-55223999
GRCh38: 1:54758326-54758326
5 PARS2 NM_152268.4(PARS2):c.1129C>T (p.Pro377Ser) SNV Uncertain significance 982976 GRCh37: 1:55223706-55223706
GRCh38: 1:54758033-54758033
6 PARS2 NM_152268.4(PARS2):c.340G>A (p.Gly114Ser) SNV Uncertain significance 983148 GRCh37: 1:55224495-55224495
GRCh38: 1:54758822-54758822
7 PARS2 NM_152268.4(PARS2):c.1091C>G (p.Pro364Arg) SNV Uncertain significance 632566 rs35201073 GRCh37: 1:55223744-55223744
GRCh38: 1:54758071-54758071
8 PARS2 NM_152268.4(PARS2):c.239T>C (p.Ile80Thr) SNV Uncertain significance 632567 rs1246773873 GRCh37: 1:55224596-55224596
GRCh38: 1:54758923-54758923
9 PARS2 NM_152268.4(PARS2):c.607G>A (p.Glu203Lys) SNV Uncertain significance 632568 rs1557762729 GRCh37: 1:55224228-55224228
GRCh38: 1:54758555-54758555

Expression for Developmental and Epileptic Encephalopathy 75

Search GEO for disease gene expression data for Developmental and Epileptic Encephalopathy 75.

Pathways for Developmental and Epileptic Encephalopathy 75

GO Terms for Developmental and Epileptic Encephalopathy 75

Sources for Developmental and Epileptic Encephalopathy 75

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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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