HLD18
MCID: LKD031
MIFTS: 26

Leukodystrophy, Hypomyelinating, 18 (HLD18)

Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Muscle diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Leukodystrophy, Hypomyelinating, 18

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 18:

Name: Leukodystrophy, Hypomyelinating, 18 57 73 28 5 38
Hld18 57 73

Characteristics:


Inheritance:

Autosomal recessive 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
variable severity
progressive disorder
early death may occur
onset in first months or years of life


HPO:

30
leukodystrophy, hypomyelinating, 18:
Onset and clinical course variable expressivity progressive


Classifications:



Summaries for Leukodystrophy, Hypomyelinating, 18

OMIM®: 57 Hypomyelinating leukodystrophy-18 (HLD18) is an autosomal recessive neurologic disorder characterized by onset of global developmental delay usually in early infancy. Affected individuals have very poor psychomotor development, including inability to sit or walk independently in the more severe cases, as well as poor or absent speech, dystonia, and spasticity. A subset of patients may develop seizures. Brain imaging shows hypomyelinating leukodystrophy affecting various brain regions; some patients may also have progressive atrophy of the corpus callosum, thalami, and cerebellum (summary by Pant et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080. (618404) (Updated 08-Dec-2022)

MalaCards based summary: Leukodystrophy, Hypomyelinating, 18, is also known as hld18. An important gene associated with Leukodystrophy, Hypomyelinating, 18 is DEGS1 (Delta 4-Desaturase, Sphingolipid 1). Affiliated tissues include cerebellum, brain and eye, and related phenotypes are seizure and spasticity

UniProtKB/Swiss-Prot: 73 An autosomal recessive disorder characterized by hypomyelinating leukodystrophy with progressive atrophy of the corpus callosum, thalami and cerebellum, and peripheral neuropathy. Clinical features include very poor psychomotor development, dystonia, severe spasticity, seizures, and failure to thrive.

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 18

Human phenotypes related to Leukodystrophy, Hypomyelinating, 18:

30 (show all 23)
# 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 failure to thrive 30 Very rare (1%) HP:0001508
4 nystagmus 30 Very rare (1%) HP:0000639
5 global developmental delay 30 Very rare (1%) HP:0001263
6 decreased nerve conduction velocity 30 Very rare (1%) HP:0000762
7 absent speech 30 Very rare (1%) HP:0001344
8 gastrostomy tube feeding in infancy 30 Very rare (1%) HP:0011471
9 demyelinating peripheral neuropathy 30 Very rare (1%) HP:0007108
10 abnormal motor nerve conduction velocity 30 Very rare (1%) HP:0040131
11 secondary microcephaly 30 Very rare (1%) HP:0005484
12 scoliosis 30 HP:0002650
13 dysarthria 30 HP:0001260
14 flexion contracture 30 HP:0001371
15 spastic tetraplegia 30 HP:0002510
16 dysmetria 30 HP:0001310
17 dystonia 30 HP:0001332
18 severe global developmental delay 30 HP:0011344
19 progressive spasticity 30 HP:0002191
20 babinski sign 30 HP:0003487
21 cerebellar atrophy 30 HP:0001272
22 atrophy/degeneration affecting the brainstem 30 HP:0007366
23 abnormal periventricular white matter morphology 30 HP:0002518

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Growth Other:
failure to thrive

Head And Neck Eyes:
nystagmus
abnormal eye movements

Muscle Soft Tissue:
hypertonia
neurogenic atrophy seen on muscle biopsy

Skeletal:
joint contractures

Head And Neck Head:
acquired microcephaly (in some patients)

Skeletal Spine:
scoliosis

Neurologic Central Nervous System:
dysarthria
spastic tetraplegia
dysmetria
dystonia
cerebellar atrophy
more
Abdomen Gastrointestinal:
feeding difficulties
tube feeding

Neurologic Peripheral Nervous System:
decreased nerve conduction velocities (in some patients)
demyelinating peripheral neuropathy (in some patients)
sural nerve biopsy shows thin myelin sheaths

Laboratory Abnormalities:
increased plasma dihydroceramide (dhcer)

Clinical features from OMIM®:

618404 (Updated 08-Dec-2022)

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 18

Search Clinical Trials, NIH Clinical Center for Leukodystrophy, Hypomyelinating, 18

Genetic Tests for Leukodystrophy, Hypomyelinating, 18

Genetic tests related to Leukodystrophy, Hypomyelinating, 18:

# Genetic test Affiliating Genes
1 Leukodystrophy, Hypomyelinating, 18 28 DEGS1

Anatomical Context for Leukodystrophy, Hypomyelinating, 18

Organs/tissues related to Leukodystrophy, Hypomyelinating, 18:

MalaCards : Cerebellum, Brain, Eye

Publications for Leukodystrophy, Hypomyelinating, 18

Articles related to Leukodystrophy, Hypomyelinating, 18:

# Title Authors PMID Year
1
DEGS1 variant causes neurological disorder. 57 5
31186544 2019
2
Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy. 57 5
30620337 2019
3
DEGS1-associated aberrant sphingolipid metabolism impairs nervous system function in humans. 57 5
30620338 2019

Variations for Leukodystrophy, Hypomyelinating, 18

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 18:

5 (show all 13)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 DEGS1 NM_003676.4(DEGS1):c.341_342del (p.Leu114fs) DEL Pathogenic
626327 rs1558209947 GRCh37: 1:224377537-224377538
GRCh38: 1:224189835-224189836
2 DEGS1 NM_003676.4(DEGS1):c.604del (p.Tyr202fs) DEL Pathogenic
626328 rs1558210191 GRCh37: 1:224377799-224377799
GRCh38: 1:224190097-224190097
3 DEGS1 NM_003676.4(DEGS1):c.852_855del (p.Tyr283_Tyr284insTer) DEL Pathogenic
1172541 GRCh37: 1:224380060-224380063
GRCh38: 1:224192358-224192361
4 DEGS1 NM_003676.4(DEGS1):c.764A>G (p.Asn255Ser) SNV Pathogenic
625852 rs768180196 GRCh37: 1:224377960-224377960
GRCh38: 1:224190258-224190258
5 DEGS1 NM_003676.4(DEGS1):c.337A>G (p.Asn113Asp) SNV Likely Pathogenic
626329 rs1280845604 GRCh37: 1:224377533-224377533
GRCh38: 1:224189831-224189831
6 DEGS1 NM_003676.4(DEGS1):c.320G>A (p.Trp107Ter) SNV Likely Pathogenic
626330 rs1382083552 GRCh37: 1:224377516-224377516
GRCh38: 1:224189814-224189814
7 DEGS1 NM_003676.4(DEGS1):c.839C>T (p.Ala280Val) SNV Likely Pathogenic
626324 rs1558211070 GRCh37: 1:224380047-224380047
GRCh38: 1:224192345-224192345
8 DEGS1 NM_003676.4(DEGS1):c.517C>T (p.Arg173Ter) SNV Likely Pathogenic
805858 rs932183417 GRCh37: 1:224377713-224377713
GRCh38: 1:224190011-224190011
9 DEGS1 NM_003676.4(DEGS1):c.397C>T (p.Arg133Trp) SNV Likely Pathogenic
805859 rs1367958450 GRCh37: 1:224377593-224377593
GRCh38: 1:224189891-224189891
10 DEGS1 NM_003676.4(DEGS1):c.565A>G (p.Asn189Asp) SNV Conflicting Interpretations Of Pathogenicity
805860 rs771864122 GRCh37: 1:224377761-224377761
GRCh38: 1:224190059-224190059
11 DEGS1 NM_003676.4(DEGS1):c.395A>G (p.His132Arg) SNV Uncertain Significance
626325 rs1558209997 GRCh37: 1:224377591-224377591
GRCh38: 1:224189889-224189889
12 DEGS1 NM_003676.4(DEGS1):c.110T>C (p.Met37Thr) SNV Uncertain Significance
805856 rs1388884067 GRCh37: 1:224377306-224377306
GRCh38: 1:224189604-224189604
13 DEGS1 NM_003676.4(DEGS1):c.878G>A (p.Trp293Ter) SNV Uncertain Significance
805857 rs1572045183 GRCh37: 1:224380086-224380086
GRCh38: 1:224192384-224192384

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 18:

73
# Symbol AA change Variation ID SNP ID
1 DEGS1 p.Asn113Asp VAR_082596
2 DEGS1 p.Arg133Trp VAR_082598
3 DEGS1 p.Asn255Ser VAR_082601
4 DEGS1 p.Ala280Val VAR_082602

Expression for Leukodystrophy, Hypomyelinating, 18

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 18.

Pathways for Leukodystrophy, Hypomyelinating, 18

GO Terms for Leukodystrophy, Hypomyelinating, 18

Sources for Leukodystrophy, Hypomyelinating, 18

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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