DESMOS
MCID: DSM002
MIFTS: 34

Desmosterolosis (DESMOS)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Desmosterolosis

MalaCards integrated aliases for Desmosterolosis:

Name: Desmosterolosis 58 54 26 60 76 38 30 13 56 6 41 74
Deficiency of 3beta-Hydroxysterol Delta24-Reductase 26
Desmos 76

Characteristics:

Orphanet epidemiological data:

60
desmosterolosis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Infancy,Neonatal; Age of death: any age,stillbirth;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
patients from 4 unrelated families have been reported (as of october 2011)
dysmorphic facial features may not be present


HPO:

33
desmosterolosis:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Desmosterolosis

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 35107Disease definitionDesmosterolosis is a very rare sterol biosynthesis disorder characterized by multiple congenital anomalies, failure to thrive, and intellectual disability, with elevated levels of desmosterol.EpidemiologyOnly 9 cases have been reported in the literature to date.Clinical descriptionDesmosterolosis presents at birth with growth restriction, spasticity with variable degrees of hand contractures, either microcephaly or relative macrocephaly, and microretrognathia. Transient neonatal seizures, nystagmus, strabismus and failure to thrive are also seen in most cases. Intellectual disability occurs in all patients and is first noted by delayed milestones for speech and adaptive, fine and gross motor development. Less common manifestations reported include hirsutism, facial dysmorphism (downslanting palpebral fissures, bilateral epicanthal folds, submucous cleft palate, and thick alveolar ridges), sensorineural hearing loss, patent arterial duct, ambiguous genitalia, bilateral clubfeet, muscle wasting, and cutis aplasia. Optic atrophy, corpus callosum agenesis and loss of white matter are also noted.EtiologyDesmosterolosis is due to mutations in the DHCR24 gene (1p32.3) encoding 3-beta-hydroxysterol delta-24-reductase. This enzyme catalyzes the conversion of desmosterol (the cholesterol precursor) to cholesterol, which is highly involved in embryonic development and morphogenesis. Reduced enzyme activity leads to the accumulation of desmosterol and a lack of cholesterol, disrupting antenatal and postnatal development.Genetic counselingDesmosterolosis is inherited in an autosomal recessive manner and genetic counseling is possible.Visit the Orphanet disease page for more resources.

MalaCards based summary : Desmosterolosis, also known as deficiency of 3beta-hydroxysterol delta24-reductase, is related to greenberg dysplasia and smith-lemli-opitz syndrome, and has symptoms including seizures and muscle spasticity. An important gene associated with Desmosterolosis is DHCR24 (24-Dehydrocholesterol Reductase), and among its related pathways/superpathways are Steroid biosynthesis and Metabolic pathways. Affiliated tissues include brain, bone and skin, and related phenotypes are agenesis of corpus callosum and intellectual disability

Genetics Home Reference : 26 Desmosterolosis is a condition that is characterized by neurological problems, such as brain abnormalities and developmental delay, and can also include other signs and symptoms.

OMIM : 58 Desmosterolosis is a rare autosomal recessive disorder characterized by multiple congenital anomalies and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells (summary by Waterham et al., 2001). (602398)

UniProtKB/Swiss-Prot : 76 Desmosterolosis: Rare autosomal recessive disorder characterized by multiple congenital anomalies and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells.

Wikipedia : 77 Desmosterolosis is a defect in cholesterol biosynthesis. It results in an accumulation of... more...

Related Diseases for Desmosterolosis

Diseases related to Desmosterolosis via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 greenberg dysplasia 11.1
2 smith-lemli-opitz syndrome 11.1
3 osteoblastoma 10.3
4 ameloblastoma 10.1
5 corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia 10.1
6 microcephaly 10.1
7 spasticity 10.1

Graphical network of the top 20 diseases related to Desmosterolosis:



Diseases related to Desmosterolosis

Symptoms & Phenotypes for Desmosterolosis

Human phenotypes related to Desmosterolosis:

60 33 (show top 50) (show all 76)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 agenesis of corpus callosum 60 33 hallmark (90%) Very frequent (99-80%) HP:0001274
2 intellectual disability 60 33 hallmark (90%) Very frequent (99-80%) HP:0001249
3 spasticity 60 33 hallmark (90%) Very frequent (99-80%) HP:0001257
4 failure to thrive 60 33 hallmark (90%) Very frequent (99-80%) HP:0001508
5 microcephaly 60 33 very rare (1%) Very frequent (99-80%) HP:0000252
6 micrognathia 60 33 very rare (1%) Very frequent (99-80%) HP:0000347
7 feeding difficulties 60 33 hallmark (90%) Very frequent (99-80%) HP:0011968
8 retrognathia 60 33 hallmark (90%) Very frequent (99-80%) HP:0000278
9 intrauterine growth retardation 60 33 hallmark (90%) Very frequent (99-80%) HP:0001511
10 muscle stiffness 60 33 hallmark (90%) Very frequent (99-80%) HP:0003552
11 rigidity 60 33 hallmark (90%) Very frequent (99-80%) HP:0002063
12 severe short stature 60 33 hallmark (90%) Very frequent (99-80%) HP:0003510
13 absent septum pellucidum 60 33 hallmark (90%) Very frequent (99-80%) HP:0001331
14 bifid uvula 60 33 hallmark (90%) Very frequent (99-80%) HP:0000193
15 submucous cleft hard palate 60 33 hallmark (90%) Very frequent (99-80%) HP:0000176
16 nystagmus 60 33 frequent (33%) Frequent (79-30%) HP:0000639
17 depressed nasal bridge 60 33 frequent (33%) Frequent (79-30%) HP:0005280
18 short nose 60 33 frequent (33%) Frequent (79-30%) HP:0003196
19 strabismus 60 33 frequent (33%) Frequent (79-30%) HP:0000486
20 ventriculomegaly 60 33 frequent (33%) Frequent (79-30%) HP:0002119
21 status epilepticus 60 33 frequent (33%) Frequent (79-30%) HP:0002133
22 low-set, posteriorly rotated ears 60 33 frequent (33%) Frequent (79-30%) HP:0000368
23 narrow mouth 60 33 frequent (33%) Frequent (79-30%) HP:0000160
24 large earlobe 60 33 frequent (33%) Frequent (79-30%) HP:0009748
25 macrocephaly 60 33 very rare (1%) Occasional (29-5%) HP:0000256
26 frontal bossing 60 33 very rare (1%) Occasional (29-5%) HP:0002007
27 hydrocephalus 60 33 occasional (7.5%) Occasional (29-5%) HP:0000238
28 splenomegaly 60 33 occasional (7.5%) Occasional (29-5%) HP:0001744
29 prominent forehead 60 33 occasional (7.5%) Occasional (29-5%) HP:0011220
30 patent ductus arteriosus 60 33 very rare (1%) Occasional (29-5%) HP:0001643
31 micromelia 60 33 occasional (7.5%) Occasional (29-5%) HP:0002983
32 epicanthus 60 33 very rare (1%) Occasional (29-5%) HP:0000286
33 metatarsus adductus 60 33 occasional (7.5%) Occasional (29-5%) HP:0001840
34 downslanted palpebral fissures 60 33 very rare (1%) Occasional (29-5%) HP:0000494
35 intestinal malrotation 60 33 occasional (7.5%) Occasional (29-5%) HP:0002566
36 ambiguous genitalia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000062
37 pachygyria 60 33 occasional (7.5%) Occasional (29-5%) HP:0001302
38 polymicrogyria 60 33 occasional (7.5%) Occasional (29-5%) HP:0002126
39 talipes 60 33 occasional (7.5%) Occasional (29-5%) HP:0001883
40 renal agenesis 60 33 occasional (7.5%) Occasional (29-5%) HP:0000104
41 osteopetrosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0011002
42 anomalous pulmonary venous return 60 33 occasional (7.5%) Occasional (29-5%) HP:0010772
43 dermal atrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0004334
44 macrogyria 60 33 occasional (7.5%) Occasional (29-5%) HP:0007227
45 low-set ears 60 33 very rare (1%) Frequent (79-30%) HP:0000369
46 cleft palate 60 33 very rare (1%) Very frequent (99-80%) HP:0000175
47 global developmental delay 33 very rare (1%) HP:0001263
48 generalized osteosclerosis 33 very rare (1%) HP:0005789
49 rhizomelia 33 very rare (1%) HP:0008905
50 aplasia/hypoplasia of the corpus callosum 33 very rare (1%) HP:0007370

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Ears:
low-set ears
posteriorly rotated ears

Neurologic Central Nervous System:
hydrocephalus
seizures
spasticity
ventriculomegaly
delayed psychomotor development, severe
more
Growth Other:
failure to thrive

Head And Neck Head:
microcephaly
macrocephaly, relative

Genitourinary External Genitalia Male:
ambiguous genitalia

Skeletal Limbs:
rhizomelic shortening

Skeletal Hands:
contractures of the hands

Laboratory Abnormalities:
elevated plasma desmosterol

Head And Neck Face:
frontal bossing
micrognathia

Head And Neck Eyes:
nystagmus
strabismus

Head And Neck Nose:
short nose
anteverted nares
hypoplastic nasal bridge

Head And Neck Mouth:
cleft palate
thick alveolar ridges
gingival nodules

Genitourinary External Genitalia Female:
ambiguous genitalia

Skeletal:
osteosclerosis
arthrogryposis

Cardiovascular Heart:
total anomalous pulmonary venous drainage (1 patient)

Clinical features from OMIM:

602398

UMLS symptoms related to Desmosterolosis:


seizures, muscle spasticity

Drugs & Therapeutics for Desmosterolosis

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of Inborn Errors of Cholesterol Synthesis and Related Disorders Recruiting NCT00046202

Search NIH Clinical Center for Desmosterolosis

Genetic Tests for Desmosterolosis

Genetic tests related to Desmosterolosis:

# Genetic test Affiliating Genes
1 Desmosterolosis 30 DHCR24

Anatomical Context for Desmosterolosis

MalaCards organs/tissues related to Desmosterolosis:

42
Brain, Bone, Skin

Publications for Desmosterolosis

Articles related to Desmosterolosis:

(show all 11)
# Title Authors Year
1
Desmosterolosis and desmosterol homeostasis in the developing mouse brain. ( 30891795 )
2019
2
Desmosterolosis presenting with multiple congenital anomalies. ( 29175559 )
2018
3
Desmosterolosis: an illustration of diagnostic ambiguity of cholesterol synthesis disorders. ( 24961299 )
2014
4
The desmosterolosis phenotype: spasticity, microcephaly and micrognathia with agenesis of corpus callosum and loss of white matter. ( 21559050 )
2011
5
Desmosterolosis-phenotypic and molecular characterization of a third case and review of the literature. ( 21671375 )
2011
6
Differential effects of cholesterol and desmosterol on the ligand binding function of the hippocampal serotonin(1A) receptor: implications in desmosterolosis. ( 19616511 )
2009
7
Desmosterolosis presenting with multiple congenital anomalies and profound developmental delay. ( 12457401 )
2002
8
Mutations in the 3beta-hydroxysterol delta24-reductase gene cause desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis. ( 11519011 )
2001
9
Retinal structure and function in an animal model that replicates the biochemical hallmarks of desmosterolosis. ( 10905631 )
2000
10
Clinical phenotype of desmosterolosis. ( 9450875 )
1998
11
Desmosterolosis: a new inborn error of cholesterol biosynthesis. ( 8709748 )
1996

Variations for Desmosterolosis

UniProtKB/Swiss-Prot genetic disease variations for Desmosterolosis:

76
# Symbol AA change Variation ID SNP ID
1 DHCR24 p.Glu191Lys VAR_012732 rs119475041
2 DHCR24 p.Asn294Thr VAR_012733 rs281797257
3 DHCR24 p.Lys306Asn VAR_012734 rs281797256
4 DHCR24 p.Tyr471Ser VAR_012735 rs28939092

ClinVar genetic disease variations for Desmosterolosis:

6 (show top 50) (show all 134)
# Gene Variation Type Significance SNP ID Assembly Location
1 DHCR24 NM_014762.4(DHCR24): c.1412A> C (p.Tyr471Ser) single nucleotide variant Pathogenic rs28939092 GRCh37 Chromosome 1, 55318045: 55318045
2 DHCR24 NM_014762.4(DHCR24): c.1412A> C (p.Tyr471Ser) single nucleotide variant Pathogenic rs28939092 GRCh38 Chromosome 1, 54852372: 54852372
3 DHCR24 NM_014762.4(DHCR24): c.881A> C (p.Asn294Thr) single nucleotide variant no interpretation for the single variant rs281797257 GRCh37 Chromosome 1, 55331115: 55331115
4 DHCR24 NM_014762.4(DHCR24): c.881A> C (p.Asn294Thr) single nucleotide variant no interpretation for the single variant rs281797257 GRCh38 Chromosome 1, 54865442: 54865442
5 DHCR24 NM_014762.4(DHCR24): c.571G> A (p.Glu191Lys) single nucleotide variant Likely pathogenic rs119475041 GRCh37 Chromosome 1, 55340807: 55340807
6 DHCR24 NM_014762.4(DHCR24): c.571G> A (p.Glu191Lys) single nucleotide variant Likely pathogenic rs119475041 GRCh38 Chromosome 1, 54875134: 54875134
7 DHCR24 NM_014762.4(DHCR24): c.918G> C (p.Lys306Asn) single nucleotide variant no interpretation for the single variant rs281797256 GRCh37 Chromosome 1, 55331078: 55331078
8 DHCR24 NM_014762.4(DHCR24): c.918G> C (p.Lys306Asn) single nucleotide variant no interpretation for the single variant rs281797256 GRCh38 Chromosome 1, 54865405: 54865405
9 DHCR24 NM_014762.4(DHCR24): c.307C> T (p.Arg103Cys) single nucleotide variant Pathogenic rs387906938 GRCh37 Chromosome 1, 55349371: 55349371
10 DHCR24 NM_014762.4(DHCR24): c.307C> T (p.Arg103Cys) single nucleotide variant Pathogenic rs387906938 GRCh38 Chromosome 1, 54883698: 54883698
11 DHCR24 NM_014762.4(DHCR24): c.281G> A (p.Arg94His) single nucleotide variant Pathogenic rs387906939 GRCh37 Chromosome 1, 55349397: 55349397
12 DHCR24 NM_014762.4(DHCR24): c.281G> A (p.Arg94His) single nucleotide variant Pathogenic rs387906939 GRCh38 Chromosome 1, 54883724: 54883724
13 DHCR24 NM_014762.4(DHCR24): c.1438G> A (p.Glu480Lys) single nucleotide variant Pathogenic rs387906940 GRCh37 Chromosome 1, 55318019: 55318019
14 DHCR24 NM_014762.4(DHCR24): c.1438G> A (p.Glu480Lys) single nucleotide variant Pathogenic rs387906940 GRCh38 Chromosome 1, 54852346: 54852346
15 DHCR24 NM_014762.4(DHCR24): c.81C> T (p.Leu27=) single nucleotide variant Conflicting interpretations of pathogenicity rs140995590 GRCh37 Chromosome 1, 55352712: 55352712
16 DHCR24 NM_014762.4(DHCR24): c.81C> T (p.Leu27=) single nucleotide variant Conflicting interpretations of pathogenicity rs140995590 GRCh38 Chromosome 1, 54887039: 54887039
17 DHCR24 NM_014762.4(DHCR24): c.*2503C> T single nucleotide variant Uncertain significance rs886046412 GRCh38 Chromosome 1, 54849730: 54849730
18 DHCR24 NM_014762.4(DHCR24): c.*2503C> T single nucleotide variant Uncertain significance rs886046412 GRCh37 Chromosome 1, 55315403: 55315403
19 DHCR24 NM_014762.4(DHCR24): c.*2119C> T single nucleotide variant Uncertain significance rs886046414 GRCh38 Chromosome 1, 54850114: 54850114
20 DHCR24 NM_014762.4(DHCR24): c.*2119C> T single nucleotide variant Uncertain significance rs886046414 GRCh37 Chromosome 1, 55315787: 55315787
21 DHCR24 NM_014762.4(DHCR24): c.*1264T> C single nucleotide variant Uncertain significance rs553462271 GRCh38 Chromosome 1, 54850969: 54850969
22 DHCR24 NM_014762.4(DHCR24): c.*1264T> C single nucleotide variant Uncertain significance rs553462271 GRCh37 Chromosome 1, 55316642: 55316642
23 DHCR24 NM_014762.4(DHCR24): c.*944C> T single nucleotide variant Uncertain significance rs79299252 GRCh38 Chromosome 1, 54851289: 54851289
24 DHCR24 NM_014762.4(DHCR24): c.*944C> T single nucleotide variant Uncertain significance rs79299252 GRCh37 Chromosome 1, 55316962: 55316962
25 DHCR24 NM_014762.4(DHCR24): c.*914G> A single nucleotide variant Uncertain significance rs140759061 GRCh38 Chromosome 1, 54851319: 54851319
26 DHCR24 NM_014762.4(DHCR24): c.*914G> A single nucleotide variant Uncertain significance rs140759061 GRCh37 Chromosome 1, 55316992: 55316992
27 DHCR24 NM_014762.4(DHCR24): c.*731T> C single nucleotide variant Uncertain significance rs116289873 GRCh38 Chromosome 1, 54851502: 54851502
28 DHCR24 NM_014762.4(DHCR24): c.*731T> C single nucleotide variant Uncertain significance rs116289873 GRCh37 Chromosome 1, 55317175: 55317175
29 DHCR24 NM_014762.4(DHCR24): c.*718G> A single nucleotide variant Uncertain significance rs74072035 GRCh38 Chromosome 1, 54851515: 54851515
30 DHCR24 NM_014762.4(DHCR24): c.*718G> A single nucleotide variant Uncertain significance rs74072035 GRCh37 Chromosome 1, 55317188: 55317188
31 DHCR24 NM_014762.4(DHCR24): c.*508T> C single nucleotide variant Uncertain significance rs886046416 GRCh38 Chromosome 1, 54851725: 54851725
32 DHCR24 NM_014762.4(DHCR24): c.*508T> C single nucleotide variant Uncertain significance rs886046416 GRCh37 Chromosome 1, 55317398: 55317398
33 DHCR24 NM_014762.4(DHCR24): c.*480C> T single nucleotide variant Uncertain significance rs576670614 GRCh38 Chromosome 1, 54851753: 54851753
34 DHCR24 NM_014762.4(DHCR24): c.*480C> T single nucleotide variant Uncertain significance rs576670614 GRCh37 Chromosome 1, 55317426: 55317426
35 DHCR24 NM_014762.4(DHCR24): c.*393G> A single nucleotide variant Uncertain significance rs146650872 GRCh38 Chromosome 1, 54851840: 54851840
36 DHCR24 NM_014762.4(DHCR24): c.*393G> A single nucleotide variant Uncertain significance rs146650872 GRCh37 Chromosome 1, 55317513: 55317513
37 DHCR24 NM_014762.4(DHCR24): c.726C> A (p.Phe242Leu) single nucleotide variant Uncertain significance rs138043637 GRCh38 Chromosome 1, 54871500: 54871500
38 DHCR24 NM_014762.4(DHCR24): c.*392C> T single nucleotide variant Uncertain significance rs116490123 GRCh38 Chromosome 1, 54851841: 54851841
39 DHCR24 NM_014762.4(DHCR24): c.*392C> T single nucleotide variant Uncertain significance rs116490123 GRCh37 Chromosome 1, 55317514: 55317514
40 DHCR24 NM_014762.4(DHCR24): c.*316T> G single nucleotide variant Uncertain significance rs74072037 GRCh38 Chromosome 1, 54851917: 54851917
41 DHCR24 NM_014762.4(DHCR24): c.*316T> G single nucleotide variant Uncertain significance rs74072037 GRCh37 Chromosome 1, 55317590: 55317590
42 DHCR24 NM_014762.4(DHCR24): c.726C> A (p.Phe242Leu) single nucleotide variant Uncertain significance rs138043637 GRCh37 Chromosome 1, 55337173: 55337173
43 DHCR24 NM_014762.4(DHCR24): c.639C> T (p.Ala213=) single nucleotide variant Uncertain significance rs143779194 GRCh38 Chromosome 1, 54871587: 54871587
44 DHCR24 NM_014762.4(DHCR24): c.639C> T (p.Ala213=) single nucleotide variant Uncertain significance rs143779194 GRCh37 Chromosome 1, 55337260: 55337260
45 DHCR24 NM_014762.4(DHCR24): c.*2555A> G single nucleotide variant Benign rs657688 GRCh38 Chromosome 1, 54849678: 54849678
46 DHCR24 NM_014762.4(DHCR24): c.*2555A> G single nucleotide variant Benign rs657688 GRCh37 Chromosome 1, 55315351: 55315351
47 DHCR24 NM_014762.4(DHCR24): c.*2514A> G single nucleotide variant Uncertain significance rs532882730 GRCh38 Chromosome 1, 54849719: 54849719
48 DHCR24 NM_014762.4(DHCR24): c.*2514A> G single nucleotide variant Uncertain significance rs532882730 GRCh37 Chromosome 1, 55315392: 55315392
49 DHCR24 NM_014762.4(DHCR24): c.*2442G> T single nucleotide variant Uncertain significance rs115017311 GRCh38 Chromosome 1, 54849791: 54849791
50 DHCR24 NM_014762.4(DHCR24): c.*2442G> T single nucleotide variant Uncertain significance rs115017311 GRCh37 Chromosome 1, 55315464: 55315464

Expression for Desmosterolosis

Search GEO for disease gene expression data for Desmosterolosis.

Pathways for Desmosterolosis

Pathways related to Desmosterolosis according to KEGG:

38
# Name Kegg Source Accession
1 Steroid biosynthesis hsa00100
2 Metabolic pathways hsa01100

GO Terms for Desmosterolosis

Sources for Desmosterolosis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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