SQSD
MCID: SQL002
MIFTS: 27

Squalene Synthase Deficiency (SQSD)

Categories: Genetic diseases, Nephrological diseases, Neuronal diseases

Aliases & Classifications for Squalene Synthase Deficiency

MalaCards integrated aliases for Squalene Synthase Deficiency:

Name: Squalene Synthase Deficiency 57 25 72 29 6 17
Neurodevelopmental Disorder with Low Cholesterol and Abnormal Urine Organic Acids 57 72
Sqsd 57 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
phenotypic variability
based on one report of 2 siblings and one unrelated boy (last curated october 2018)

Inheritance:
autosomal recessive


HPO:

31
squalene synthase deficiency:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Squalene Synthase Deficiency

OMIM® : 57 Squalene synthase deficiency is an autosomal recessive disorder characterized by profound developmental delay, brain abnormalities, 2/3 syndactyly of the toes, and facial dysmorphisms, as well as low total and LDL-cholesterol and abnormal urine organic acids (Coman et al., 2018). Squalene synthase deficiency has been reported in 3 patients from 2 families. (618156) (Updated 20-May-2021)

MalaCards based summary : Squalene Synthase Deficiency, also known as neurodevelopmental disorder with low cholesterol and abnormal urine organic acids, is related to optic nerve hypoplasia, bilateral and chromosome 2q35 duplication syndrome. An important gene associated with Squalene Synthase Deficiency is FDFT1 (Farnesyl-Diphosphate Farnesyltransferase 1). Affiliated tissues include bone, and related phenotypes are constipation and depressed nasal bridge

UniProtKB/Swiss-Prot : 72 Squalene synthase deficiency: An autosomal recessive disorder characterized by profound developmental delay, brain abnormalities, 2/3 syndactyly of the toes, facial dysmorphisms, low total and LDL-cholesterol, and abnormal urine organic acids.

GeneReviews: NBK553533

Related Diseases for Squalene Synthase Deficiency

Diseases related to Squalene Synthase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 optic nerve hypoplasia, bilateral 10.0
2 chromosome 2q35 duplication syndrome 10.0
3 cryptorchidism, unilateral or bilateral 10.0
4 smith-lemli-opitz syndrome 10.0
5 opitz gbbb syndrome, type i 10.0
6 alacrima, achalasia, and mental retardation syndrome 10.0
7 hypospadias 10.0
8 constipation 10.0
9 sleep disorder 10.0
10 dysphagia 10.0
11 seizure disorder 10.0
12 spasticity 10.0
13 cerebral visual impairment 10.0

Graphical network of the top 20 diseases related to Squalene Synthase Deficiency:



Diseases related to Squalene Synthase Deficiency

Symptoms & Phenotypes for Squalene Synthase Deficiency

Human phenotypes related to Squalene Synthase Deficiency:

31 (show all 31)
# Description HPO Frequency HPO Source Accession
1 constipation 31 very rare (1%) HP:0002019
2 depressed nasal bridge 31 very rare (1%) HP:0005280
3 macrotia 31 very rare (1%) HP:0000400
4 dry skin 31 very rare (1%) HP:0000958
5 intrauterine growth retardation 31 very rare (1%) HP:0001511
6 retrognathia 31 very rare (1%) HP:0000278
7 micrognathia 31 very rare (1%) HP:0000347
8 failure to thrive in infancy 31 very rare (1%) HP:0001531
9 epicanthus 31 very rare (1%) HP:0000286
10 bicuspid aortic valve 31 very rare (1%) HP:0001647
11 irritability 31 very rare (1%) HP:0000737
12 slender long bone 31 very rare (1%) HP:0003100
13 elbow flexion contracture 31 very rare (1%) HP:0002987
14 low-set, posteriorly rotated ears 31 very rare (1%) HP:0000368
15 hypospadias 31 very rare (1%) HP:0000047
16 cutaneous photosensitivity 31 very rare (1%) HP:0000992
17 polymicrogyria 31 very rare (1%) HP:0002126
18 profound global developmental delay 31 very rare (1%) HP:0012736
19 hypocholesterolemia 31 very rare (1%) HP:0003146
20 decreased ldl cholesterol concentration 31 very rare (1%) HP:0003563
21 hypoplasia of the corpus callosum 31 very rare (1%) HP:0002079
22 knee flexion contracture 31 very rare (1%) HP:0006380
23 gastrostomy tube feeding in infancy 31 very rare (1%) HP:0011471
24 optic nerve hypoplasia 31 very rare (1%) HP:0000609
25 cerebral visual impairment 31 very rare (1%) HP:0100704
26 2-3 toe syndactyly 31 very rare (1%) HP:0004691
27 bilateral cryptorchidism 31 very rare (1%) HP:0008689
28 seizure 31 very rare (1%) HP:0001250
29 increased circulating farnesol concentration 31 very rare (1%) HP:0033083
30 abnormality of hair pigmentation 31 HP:0009887
31 elevated circulating methylsuccinic acid concentration 31 HP:0033146

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Other:
failure to thrive
iugr

Head And Neck Nose:
depressed nasal bridge
square nasal tip

Neurologic Behavioral Psychiatric Manifestations:
irritability
poor sleep initiation and maintenance

Neurologic Central Nervous System:
polymicrogyria
hypoplastic corpus callosum
developmental delay, profound
cortical visual impairment
white matter loss
more
Head And Neck Mouth:
hypersalivation

Head And Neck Face:
facial dysmorphisms, mild

Skin Nails Hair Skin:
dry skin photosensitivity

Laboratory Abnormalities:
elevated mevalonate lactone, methylsuccinate and multiple branched-chain dicarboxylic acids
low blood total cholesterol (tc)
reduced low-density lipoprotein cholesterol (ldl-c)
elevated blood farnesol

Abdomen Gastrointestinal:
constipation
gastrostomy tube feeding required

Head And Neck Eyes:
visual impairment
optic nerve hypoplasia, bilateral

Genitourinary External Genitalia Male:
hypospadias
cryptorchidism, bilateral

Skeletal Feet:
syndactyly of second and third toes

Skeletal:
gracile bones

Skeletal Limbs:
fixed flexion contractures of knees
flexion deformity of elbows

Skin Nails Hair Hair:
lack of hair pigment seen on light and electron microscopy

Clinical features from OMIM®:

618156 (Updated 20-May-2021)

Drugs & Therapeutics for Squalene Synthase Deficiency

Search Clinical Trials , NIH Clinical Center for Squalene Synthase Deficiency

Genetic Tests for Squalene Synthase Deficiency

Genetic tests related to Squalene Synthase Deficiency:

# Genetic test Affiliating Genes
1 Squalene Synthase Deficiency 29 FDFT1

Anatomical Context for Squalene Synthase Deficiency

MalaCards organs/tissues related to Squalene Synthase Deficiency:

40
Bone

Publications for Squalene Synthase Deficiency

Articles related to Squalene Synthase Deficiency:

# Title Authors PMID Year
1
Squalene Synthase Deficiency: Clinical, Biochemical, and Molecular Characterization of a Defect in Cholesterol Biosynthesis. 25 6 57 61
29909962 2018
2
Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome. 25
30723320 2019
3
Molecular mechanisms involved in farnesol-induced apoptosis. 25
19520495 2010
4
Squalene synthase: a critical enzyme in the cholesterol biosynthesis pathway. 25
19054015 2009
5
Structure and regulation of mammalian squalene synthase. 25
11111077 2000
6
Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis. 25
10896663 2000
7
Gas chromatography-mass spectrometric method for quantitative determination in human urine of dicarboxylic (dioic) acids produced in the body as a consequence of cholesterol biosynthesis inhibition. 25
9657220 1998
8
Localization of the squalene synthase gene (FDFT1) to human chromosome 8p22-p23.1. 25
8020937 1994
9
Conservation between human and fungal squalene synthetases: similarities in structure, function, and regulation. 25
8474436 1993
10
Squalene Synthase Deficiency 61
32027475 2020

Variations for Squalene Synthase Deficiency

ClinVar genetic disease variations for Squalene Synthase Deficiency:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FDFT1 NC_000008.10:g.11667760_11787743del Deletion Pathogenic 587360 GRCh37:
GRCh38:
2 overlap with 4 genes NC_000008.10:g.11667760_11787743del119984 Deletion Likely pathogenic 599353 GRCh37: 8:11667760-11787743
GRCh38: 8:11810251-11930234
3 FDFT1 NM_004462.5(FDFT1):c.899T>A (p.Leu300Ter) SNV Likely pathogenic 996898 GRCh37: 8:11689046-11689046
GRCh38: 8:11831537-11831537
4 FDFT1 NM_004462.5(FDFT1):c.880-24_880-23delinsAG Indel Likely pathogenic 587361 rs1563339323 GRCh37: 8:11689003-11689004
GRCh38: 8:11831494-11831495
5 FDFT1 NM_001287742.1(FDFT1):c.-75+131_-75+146del Deletion Likely pathogenic 587362 rs1563290033 GRCh37: 8:11660095-11660110
GRCh38: 8:11802586-11802601
6 FDFT1 NM_004462.5(FDFT1):c.19C>A (p.Leu7Ile) SNV Uncertain significance 1028763 GRCh37: 8:11660360-11660360
GRCh38: 8:11802851-11802851
7 FDFT1 NM_004462.5(FDFT1):c.670C>G (p.Gln224Glu) SNV Uncertain significance 1028764 GRCh37: 8:11683692-11683692
GRCh38: 8:11826183-11826183

Expression for Squalene Synthase Deficiency

Search GEO for disease gene expression data for Squalene Synthase Deficiency.

Pathways for Squalene Synthase Deficiency

GO Terms for Squalene Synthase Deficiency

Sources for Squalene Synthase Deficiency

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