HLD18
MCID: LKD031
MIFTS: 25

Leukodystrophy, Hypomyelinating, 18 (HLD18)

Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 18

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 18:

Name: Leukodystrophy, Hypomyelinating, 18 57 73 29 6
Hld18 57 73

Characteristics:

OMIM®:

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

Miscellaneous:
variable severity
progressive disorder
early death may occur
onset in first months or years of life


HPO:

31
leukodystrophy, hypomyelinating, 18:
Inheritance autosomal recessive inheritance
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 05-Mar-2021)

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 and eye, and related phenotypes are spasticity and failure to thrive

UniProtKB/Swiss-Prot : 73 Leukodystrophy, hypomyelinating, 18: 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:

31 (show all 23)
# Description HPO Frequency HPO Source Accession
1 spasticity 31 very rare (1%) HP:0001257
2 failure to thrive 31 very rare (1%) HP:0001508
3 nystagmus 31 very rare (1%) HP:0000639
4 global developmental delay 31 very rare (1%) HP:0001263
5 decreased nerve conduction velocity 31 very rare (1%) HP:0000762
6 absent speech 31 very rare (1%) HP:0001344
7 postnatal microcephaly 31 very rare (1%) HP:0005484
8 gastrostomy tube feeding in infancy 31 very rare (1%) HP:0011471
9 demyelinating peripheral neuropathy 31 very rare (1%) HP:0007108
10 abnormal motor nerve conduction velocity 31 very rare (1%) HP:0040131
11 seizure 31 very rare (1%) HP:0001250
12 scoliosis 31 HP:0002650
13 dysarthria 31 HP:0001260
14 flexion contracture 31 HP:0001371
15 spastic tetraplegia 31 HP:0002510
16 dysmetria 31 HP:0001310
17 dystonia 31 HP:0001332
18 severe global developmental delay 31 HP:0011344
19 progressive spasticity 31 HP:0002191
20 babinski sign 31 HP:0003487
21 cerebellar atrophy 31 HP:0001272
22 abnormality of the periventricular white matter 31 HP:0002518
23 atrophy/degeneration affecting the brainstem 31 HP:0007366

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
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 05-Mar-2021)

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 29 DEGS1

Anatomical Context for Leukodystrophy, Hypomyelinating, 18

MalaCards organs/tissues related to Leukodystrophy, Hypomyelinating, 18:

40
Cerebellum, Eye

Publications for Leukodystrophy, Hypomyelinating, 18

Articles related to Leukodystrophy, Hypomyelinating, 18:

# Title Authors PMID Year
1
DEGS1 variant causes neurological disorder. 57 6
31186544 2019
2
Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy. 57 6
30620337 2019
3
DEGS1-associated aberrant sphingolipid metabolism impairs nervous system function in humans. 6 57
30620338 2019

Variations for Leukodystrophy, Hypomyelinating, 18

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 18:

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

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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