LEUDEN
MCID: LKN030
MIFTS: 24

Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Syndrome (LEUDEN)

Categories: Genetic diseases, Mental diseases, Neuronal diseases
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Aliases & Classifications for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic...

MalaCards integrated aliases for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Syndrome:

Name: Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Syndrome 57 73 28 5 38
Leuden Syndrome 57 73
Leuden 57 73

Characteristics:


Inheritance:

Autosomal dominant 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
onset in infancy
progressive disorder
de novo mutation
episodic neurologic regression is associated with fever or illness


Classifications:



Summaries for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic...

OMIM®: 57 Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome (LEUDEN) is characterized by global developmental delay apparent in early childhood, followed by episodic neurologic regression or decompensation associated with systemic stress, such as febrile infection. Affected individuals have hypotonia, gait difficulties or ataxia, poor or absent speech with dysarthria, and variable motor abnormalities, including spasticity, dystonia, extrapyramidal signs, and tremor. Many patients have seizures. Brain imaging shows diffuse white matter abnormalities, poor myelination, thin corpus callosum, and generalized cerebral atrophy with enlarged ventricles. The clinical features of the disorder and the abnormal brain imaging findings are progressive (summary by Mao et al., 2020). (618877) (Updated 08-Dec-2022)

MalaCards based summary: Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Syndrome, is also known as leuden syndrome. An important gene associated with Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Syndrome is EIF2AK2 (Eukaryotic Translation Initiation Factor 2 Alpha Kinase 2). Affiliated tissues include brain and spinal cord, and related phenotypes are seizure and spasticity

UniProtKB/Swiss-Prot: 73 An autosomal dominant disorder characterized by global developmental delay apparent in early childhood, cognitive impairment, ataxia, poor or absent speech with dysarthria, hypotonia, hypertonia, extrapyramidal signs, tremor, and abnormal involuntary movements. Affected individuals also exhibit neurological regression in the setting of febrile illness or infection. Many patients have seizures. Brain imaging shows diffuse white matter abnormalities with poor myelination.

Related Diseases for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic...

Symptoms & Phenotypes for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic...

Human phenotypes related to Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Syndrome:

30 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizure 30 Very rare (1%) HP:0001250
2 spasticity 30 Very rare (1%) HP:0001257
3 dysarthria 30 Very rare (1%) HP:0001260
4 hypotonia 30 Very rare (1%) HP:0001252
5 bowel incontinence 30 Very rare (1%) HP:0002607
6 microcephaly 30 Very rare (1%) HP:0000252
7 myoclonus 30 Very rare (1%) HP:0001336
8 absent speech 30 Very rare (1%) HP:0001344
9 mask-like facies 30 Very rare (1%) HP:0000298
10 dystonia 30 Very rare (1%) HP:0001332
11 hemiballismus 30 Very rare (1%) HP:0100248
12 polymicrogyria 30 Very rare (1%) HP:0002126
13 gait ataxia 30 Very rare (1%) HP:0002066
14 rigidity 30 Very rare (1%) HP:0002063
15 choreoathetosis 30 Very rare (1%) HP:0001266
16 gastroparesis 30 Very rare (1%) HP:0002578
17 urinary incontinence 30 Very rare (1%) HP:0000020
18 parkinsonism 30 Very rare (1%) HP:0001300
19 truncal ataxia 30 Very rare (1%) HP:0002078
20 bradykinesia 30 Very rare (1%) HP:0002067
21 head titubation 30 Very rare (1%) HP:0002599
22 inability to walk 30 Very rare (1%) HP:0002540
23 delayed cns myelination 30 Very rare (1%) HP:0002188
24 cerebral atrophy 30 HP:0002059
25 hypoplasia of the corpus callosum 30 HP:0002079

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
spasticity
ataxia
dysarthria
tremor
hypotonia
more
Growth Other:
intrauterine growth retardation
poor overall growth

Skeletal Hands:
fifth finger clinodactyly

Head And Neck Head:
decreased head circumference, progressive (in some patients)

Head And Neck Eyes:
nystagmus
strabismus
hypotelorism
astigmatism
epicanthal folds

Head And Neck Face:
micrognathia
short philtrum
dysmorphic facial features, variable (in some patients)

Skeletal Feet:
fifth toe clinodactyly

Skeletal:
contractures, progressive (in some patients)

Clinical features from OMIM®:

618877 (Updated 08-Dec-2022)

Drugs & Therapeutics for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic...

Search Clinical Trials, NIH Clinical Center for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Syndrome

Genetic Tests for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic...

Genetic tests related to Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Syndrome:

# Genetic test Affiliating Genes
1 Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Syndrome 28 EIF2AK2

Anatomical Context for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic...

Organs/tissues related to Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Syndrome:

MalaCards : Brain, Spinal Cord

Publications for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic...

Articles related to Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Syndrome:

# Title Authors PMID Year
1
De novo EIF2AK1 and EIF2AK2 Variants Are Associated with Developmental Delay, Leukoencephalopathy, and Neurologic Decompensation. 57 5
32197074 2020
2
EIF2AK2-related Neurodevelopmental Disorder With Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Mimics Pelizaeus-Merzbacher Disease. 62
33553620 2021

Variations for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic...

ClinVar genetic disease variations for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Syndrome:

5 (show all 12)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 EIF2AK2 NM_001135651.3(EIF2AK2):c.452A>G (p.Gln151Arg) SNV Likely Pathogenic
1174083 GRCh37: 2:37366838-37366838
GRCh38: 2:37139695-37139695
2 EIF2AK2 NM_001135651.3(EIF2AK2):c.1382C>G (p.Ser461Cys) SNV Conflicting Interpretations Of Pathogenicity
818200 rs1572996700 GRCh37: 2:37336434-37336434
GRCh38: 2:37109291-37109291
3 EIF2AK2 NM_001135651.3(EIF2AK2):c.325G>T (p.Ala109Ser) SNV Uncertain Significance
872962 rs1675334390 GRCh37: 2:37368760-37368760
GRCh38: 2:37141617-37141617
4 EIF2AK2 NM_001135651.3(EIF2AK2):c.95A>G (p.Asn32Ser) SNV Uncertain Significance
872963 rs1675604381 GRCh37: 2:37374855-37374855
GRCh38: 2:37147712-37147712
5 EIF2AK2 NM_001135651.3(EIF2AK2):c.290C>T (p.Ser97Phe) SNV Uncertain Significance
813275 rs1573031939 GRCh37: 2:37368795-37368795
GRCh38: 2:37141652-37141652
6 EIF2AK2 NM_001135651.3(EIF2AK2):c.326C>T (p.Ala109Val) SNV Uncertain Significance
813274 rs1573031858 GRCh37: 2:37368759-37368759
GRCh38: 2:37141616-37141616
7 EIF2AK2 NM_001135651.3(EIF2AK2):c.971A>G (p.Asn324Ser) SNV Uncertain Significance
1342569 GRCh37: 2:37349745-37349745
GRCh38: 2:37122602-37122602
8 EIF2AK2 NM_001135651.3(EIF2AK2):c.268A>G (p.Thr90Ala) SNV Uncertain Significance
1696435 GRCh37: 2:37368817-37368817
GRCh38: 2:37141674-37141674
9 EIF2AK2 NM_001135651.3(EIF2AK2):c.31A>C (p.Met11Leu) SNV Uncertain Significance
804246 rs1363544084 GRCh37: 2:37374919-37374919
GRCh38: 2:37147776-37147776
10 EIF2AK2 NM_001135651.3(EIF2AK2):c.398A>T (p.Tyr133Phe) SNV Uncertain Significance
804253 rs1573029592 GRCh37: 2:37366892-37366892
GRCh38: 2:37139749-37139749
11 EIF2AK2 NM_001135651.3(EIF2AK2):c.1631A>G (p.Glu544Gly) SNV Uncertain Significance
1707617 GRCh37: 2:37334441-37334441
GRCh38: 2:37107298-37107298
12 EIF2AK2 NM_001135651.3(EIF2AK2):c.973G>A (p.Gly325Ser) SNV Uncertain Significance
818084 rs1573010519 GRCh37: 2:37349743-37349743
GRCh38: 2:37122600-37122600

Expression for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic...

Search GEO for disease gene expression data for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Syndrome.

Pathways for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic...

GO Terms for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic...

Sources for Leukoencephalopathy, Developmental Delay, and Episodic Neurologic...

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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