SWILS
MCID: SLW006
MIFTS: 44

Saul-Wilson Syndrome (SWILS)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Saul-Wilson Syndrome

MalaCards integrated aliases for Saul-Wilson Syndrome:

Name: Saul-Wilson Syndrome 57 11 24 42 73 14
Microcephalic Osteodysplastic Dysplasia, Saul-Wilson Type 11 58 28 5
Microcephalic Osteodysplastic Dysplasia 57 24 42 73
Swils 57 11 73
Microcephalic Osteodysplastic Dysplasia Saul Wilson Type 42

Characteristics:


Inheritance:

Saul-Wilson Syndrome: Autosomal dominant 57
Microcephalic Osteodysplastic Dysplasia, Saul-Wilson Type: Autosomal recessive 58

Prevelance:

Microcephalic Osteodysplastic Dysplasia, Saul-Wilson Type: <1/1000000 (Worldwide) 58

Age Of Onset:

Microcephalic Osteodysplastic Dysplasia, Saul-Wilson Type: Neonatal 58

GeneReviews:

24
Penetrance Penetrance is thought to be 100%.

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Saul-Wilson Syndrome

MedlinePlus Genetics: 42 Saul-Wilson syndrome is characterized by short stature (dwarfism) and other skeletal abnormalities. The growth problems in Saul-Wilson syndrome are called primordial, which means they begin before birth; affected individuals show slow prenatal growth (intrauterine growth retardation). After birth, affected individuals continue to grow at a very slow rate, with the average adult height being 3 feet, 6 inches (107 centimeters).Individuals with Saul-Wilson syndrome have distinctive facial features that often include a prominent forehead, sparse scalp hair and eyebrows, prominent scalp veins, a narrow nasal bridge, a beaked nose, a wide area separating the nostrils (broad columella), a thin upper lip, and a small lower jaw (micrognathia). This combination of facial features can give affected individuals an appearance of premature aging, particularly in infancy, that is sometimes described as progeroid.Additional skeletal abnormalities in Saul-Wilson syndrome include abnormalities in the structure of the long bones, short fingers and toes, an inward- and downward-turning foot (clubfoot), an abnormality of the hip joint that causes a decreased angle between the head and shaft of the upper leg bones (coxa vara), or flattened bones of the spine (platyspondyly) and other spinal abnormalities. Some affected individuals have bones that are unusually fragile, resulting in bone fractures that occur with little or no trauma. Adults with Saul-Wilson syndrome may experience joint pain (osteoarthritis) due to breakdown (degeneration) of the joints.Children with Saul-Wilson syndrome often have hearing loss, clouding of the lenses of the eyes (cataracts), or a blue tint to the whites of the eyes (blue sclerae). They may also have retinitis pigmentosa, in which breakdown of the light-sensitive layer (retina) at the back of the eye can cause vision loss. Individuals with Saul-Wilson syndrome may have early delay of speech and motor development, but they usually have normal intelligence.In Saul-Wilson syndrome, levels of white blood cells can vary from normal to low (intermittent neutropenia). Neutropenia makes it more difficult for the body to fight off foreign invaders such as bacteria and viruses, and may contribute to recurrent respiratory infections that occur in childhood in some individuals with Saul-Wilson syndrome.

MalaCards based summary: Saul-Wilson Syndrome, also known as microcephalic osteodysplastic dysplasia, saul-wilson type, is related to osteochondrodysplasia and clubfoot. An important gene associated with Saul-Wilson Syndrome is COG4 (Component Of Oligomeric Golgi Complex 4), and among its related pathways/superpathways are Vesicle-mediated transport and Golgi-to-ER retrograde transport. Affiliated tissues include bone, eye and retina, and related phenotypes are frontal bossing and cataract

OMIM®: 57 Saul-Wilson syndrome (SWILS) is a rare skeletal dysplasia with characteristic dysmorphic and radiographic findings, as well as early developmental delay, primarily involving speech, with eventual normal cognition. Clinical findings include marked short stature, prominent forehead with an enlarged anterior fontanel, prominent eyes with cataracts, narrow nasal bridge with a convex nasal ridge, micrognathia, clubfoot, brachydactyly, and short distal phalanges of fingers. Radiographic changes include platyspondyly, irregular end plates of vertebral bodies, and hypoplasia of the odontoid process with cervical instability in the spine, coxa valga, overtubulation, metaphyseal flaring and megaepiphyses in the long bones, while the hands and feet exhibit short phalanges, metacarpals and metatarsals, cone-shaped epiphyses of phalanges, and accessory ossification centers of metacarpals and metatarsals (summary by Ferreira et al., 2018). (618150) (Updated 24-Oct-2022)

UniProtKB/Swiss-Prot: 73 A rare skeletal dysplasia with characteristic dysmorphic and radiographic findings, as well as early developmental delay, primarily involving speech, with eventual normal cognition. Clinical findings include marked short stature, prominent forehead with an enlarged anterior fontanel, prominent eyes with cataracts, narrow nasal bridge with a convex nasal ridge, micrognathia, clubfoot, brachydactyly, and short distal phalanges of fingers. Radiographic changes include platyspondyly, irregular end plates of vertebral bodies, and hypoplasia of the odontoid process with cervical instability in the spine, coxa valga, overtubulation, metaphyseal flaring and megaepiphyses in the long bones, while the hands and feet exhibit short phalanges, metacarpals and metatarsals, cone-shaped epiphyses of phalanges, and accessory ossification centers of metacarpals and metatarsals.

Orphanet: 58 Microcephalic osteodysplastic dysplasia, Saul-Wilson type is a skeletal dysplasia characterized by a distinct facial phenotype, short stature, brachydactyly, clubfoot deformities, cataracts, and microcephaly. It has been described in four patients. Facial features include frontal bossing with a depression over the metopic suture, a narrow nasal root with a beaked nose, and midfacial hypoplasia with prominent eyes. Characteristic radiographic findings are observed (irregularities of the vertebral bodies, hypoplasia of the odontoid process, short phalanges, coning several epiphyses etc.).

Disease Ontology: 11 A bone development disease characterized by early developmental delay primarily involving speech, distinct facial features, short stature, brachydactyly, clubfoot deformities, cataracts, and microcephaly that has material basis in heterozygous mutation in COG4 on chromosome 16q22.1.

GeneReviews: NBK554080

Related Diseases for Saul-Wilson Syndrome

Diseases related to Saul-Wilson Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 39)
# Related Disease Score Top Affiliating Genes
1 osteochondrodysplasia 30.3 DCN COG4 CHST3 CHST14
2 clubfoot 30.2 COG4 CHST3 CHST14
3 congenital disorder of glycosylation, type iij 29.7 CRYAA COG7 COG5 COG4 COG3 COG1
4 isolated growth hormone deficiency, type ia 10.3
5 microcephaly 10.3
6 brachydactyly 10.3
7 cataract 10.3
8 spinal muscular atrophy, distal, autosomal recessive, 3 10.2 COG4 COG1
9 congenital disorder of glycosylation, type iig 10.2 COG5 COG1
10 retinitis pigmentosa 10.1
11 odontoid hypoplasia 10.1
12 seckel syndrome 10.1
13 cone dystrophy 10.1
14 spondyloepimetaphyseal dysplasia 10.1
15 neutropenia 10.1
16 fundus dystrophy 10.1
17 hip subluxation 10.1
18 progressive cone dystrophy 10.1
19 inherited retinal disorder 10.1
20 cone-rod dystrophy, x-linked, 2 10.0 COG5 COG4 COG3 COG1
21 larsen-like syndrome b3gat3 type 10.0 CHST3 CHST14
22 juvenile glaucoma 10.0 TGDS CRYAA
23 macular dystrophy, corneal 10.0 DCN CHST3
24 desbuquois dysplasia 10.0 CHST3 CHST14
25 marinesco-sjogren syndrome 10.0 TMCO4 CRYAA COG4
26 congenital disorder of glycosylation, type iii 9.9 COG7 COG5 COG4 COG1
27 temtamy preaxial brachydactyly syndrome 9.9 TGDS CHST3 CHST14
28 granulomatous disease, chronic, x-linked 9.9 COG7 COG1
29 congenital disorder of glycosylation, type iil 9.8 COG7 COG5 COG4 COG3 COG1
30 congenital disorder of glycosylation, type iih 9.8 COG7 COG5 COG4 COG3 COG1
31 ehlers-danlos syndrome, musculocontractural type, 2 9.8 MIR3922 CHST14
32 immunodeficiency 47 9.8 COG7 COG5 COG4 COG3 COG1
33 geroderma osteodysplasticum 9.7 DCN COG7 COG4 COG3 CHST14
34 brachyolmia 9.7 MIR3922 CHST3
35 keipert syndrome 9.7 MIR3922 GPC2 CRYAA
36 ehlers-danlos syndrome, musculocontractural type, 1 9.7 MIR3922 CHST3 CHST14
37 congenital disorder of glycosylation, type in 9.5 LMAN1 COG7 COG5 COG4 COG3 COG1
38 larsen syndrome 9.4 TGDS MIR3922 COG4 CHST3 CHST14
39 spondyloepiphyseal dysplasia with congenital joint dislocations 9.2 TGDS MIR3922 DCN COG4 CHST3 CHST14

Graphical network of the top 20 diseases related to Saul-Wilson Syndrome:



Diseases related to Saul-Wilson Syndrome

Symptoms & Phenotypes for Saul-Wilson Syndrome

Human phenotypes related to Saul-Wilson Syndrome:

58 30 (show all 35)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 frontal bossing 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002007
2 cataract 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000518
3 microcephaly 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000252
4 short stature 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0004322
5 talipes equinovarus 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001762
6 platyspondyly 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000926
7 proptosis 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000520
8 malar flattening 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000272
9 convex nasal ridge 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000444
10 small hand 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0200055
11 narrow nasal bridge 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000446
12 short palm 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0004279
13 cone-shaped epiphyses of the phalanges of the hand 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0010230
14 hypoplasia of the odontoid process 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0003311
15 irregularity of vertebral bodies 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0004582
16 overhanging nasal tip 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0011833
17 global developmental delay 30 HP:0001263
18 delayed speech and language development 30 HP:0000750
19 pectus carinatum 30 HP:0000768
20 prominent forehead 30 HP:0011220
21 intrauterine growth retardation 30 HP:0001511
22 postnatal growth retardation 30 HP:0008897
23 micrognathia 30 HP:0000347
24 pectus excavatum 30 HP:0000767
25 motor delay 30 HP:0001270
26 nyctalopia 30 HP:0000662
27 neutropenia 30 HP:0001875
28 short distal phalanx of finger 30 HP:0009882
29 coxa valga 30 HP:0002673
30 blue sclerae 30 HP:0000592
31 wide anterior fontanel 30 HP:0000260
32 short metacarpal 30 HP:0010049
33 short metatarsal 30 HP:0010743
34 flared metaphysis 30 HP:0003015
35 prominent superficial veins 30 HP:0001015

Symptoms via clinical synopsis from OMIM®:

57 (Updated 24-Oct-2022)
Chest External Features:
pectus carinatum
pectus excavatum

Head And Neck Head:
prominent forehead
large anterior fontanel

Head And Neck Face:
micrognathia
progeroid appearance
prominent veins

Skeletal Spine:
platyspondyly
dens hypoplasia

Head And Neck Nose:
convex nasal ridge
narrow nasal bridge

Head And Neck Eyes:
blue sclerae
cataracts
night blindness
prominent eyes
retinal pigmentary changes

Skeletal Feet:
short metatarsals
talipes equinovarus (clubfoot)

Head And Neck Ears:
hearing loss, sensorineural, mixed or conductive

Growth Height:
short stature

Growth Other:
postnatal growth retardation
prenatal growth retardation

Neurologic Central Nervous System:
motor delay
developmental delay
speech delay
normal cognition

Hematology:
neutropenia

Skeletal Pelvis:
coxa valga

Skeletal Hands:
short metacarpals
short distal phalanges
cone-shaped epiphyses of phalanges

Skeletal Limbs:
metaphyseal flaring of long bones
overtubulation of long bones
megaepiphyses of the long bones
dysplastic proximal radius

Clinical features from OMIM®:

618150 (Updated 24-Oct-2022)

Drugs & Therapeutics for Saul-Wilson Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Primordial Registry at Nemours/Alfred I. duPont Hospital for Children Recruiting NCT04569149

Search NIH Clinical Center for Saul-Wilson Syndrome

Genetic Tests for Saul-Wilson Syndrome

Genetic tests related to Saul-Wilson Syndrome:

# Genetic test Affiliating Genes
1 Microcephalic Osteodysplastic Dysplasia, Saul-Wilson Type 28 COG4

Anatomical Context for Saul-Wilson Syndrome

Organs/tissues related to Saul-Wilson Syndrome:

MalaCards : Bone, Eye, Retina

Publications for Saul-Wilson Syndrome

Articles related to Saul-Wilson Syndrome:

(show all 20)
# Title Authors PMID Year
1
A Recurrent De Novo Heterozygous COG4 Substitution Leads to Saul-Wilson Syndrome, Disrupted Vesicular Trafficking, and Altered Proteoglycan Glycosylation. 62 24 57 5
30290151 2018
2
Microcephalic osteodysplastic dysplasia. 62 24 57 5
8074143 1994
3
A "new" skeletal dysplasia in two unrelated boys. 24 57 5
2309787 1990
4
Defining the clinical phenotype of Saul-Wilson syndrome. 62 24
31949312 2020
5
Progressive hip joint subluxation in Saul-Wilson syndrome. 62 24
26239279 2015
6
Best practices in peri-operative management of patients with skeletal dysplasias. 24
28763154 2017
7
Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study. 24
21917867 2011
8
Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children. 24
20103654 2010
9
Severe Cranio-Cervical Stenosis in a Child with Saul-Wilson Syndrome: A Case Report. 62
35455576 2022
10
Corrigendum: Saul-Wilson Syndrome Missense Allele Does Not Show Obvious Golgi Defects in a C. elegans Model. 62
33791595 2021
11
Saul-Wilson Syndrome Missense Allele Does Not Show Obvious Golgi Defects in a C. elegans Model. 62
33688625 2021
12
A Dominant Heterozygous Mutation in COG4 Causes Saul-Wilson Syndrome, a Primordial Dwarfism, and Disrupts Zebrafish Development via Wnt Signaling. 62
34595172 2021
13
Development and Initial Characterization of Cellular Models for COG Complex-Related CDG-II Diseases. 62
34603392 2021
14
Growth in individuals with Saul-Wilson syndrome. 62
32652690 2020
15
Saul-Wilson Syndrome 62
32078278 2020
16
Anesthetic Considerations in Saul-Wilson Syndrome, a Rare Skeletal Dysplasia: A Case Report. 62
30907751 2019
17
COMMENTARY-The Saul-Wilson syndrome from its early days until now. 62
30548960 2019
18
Two coexisting liquid phases in switchable ionic liquids. 62
28664967 2017
19
Total shoulder arthroplasty in a patient with microcephalic osteodysplastic dysplasia: a case report with 4-year outcomes. 62
26927438 2016
20
Safety words inventory and literacy screener: standardization and validation. 62
12462320 2002

Variations for Saul-Wilson Syndrome

ClinVar genetic disease variations for Saul-Wilson Syndrome:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 COG4 NM_015386.3(COG4):c.1546G>A (p.Gly516Arg) SNV Pathogenic
Pathogenic
449730 rs1555575860 GRCh37: 16:70530270-70530270
GRCh38: 16:70496367-70496367
2 COG4 NM_015386.3(COG4):c.373C>T (p.Arg125Cys) SNV Uncertain Significance
1077174 GRCh37: 16:70548409-70548409
GRCh38: 16:70514506-70514506
3 COG4 NM_015386.3(COG4):c.490C>T (p.Arg164Cys) SNV Uncertain Significance
1326920 GRCh37: 16:70548292-70548292
GRCh38: 16:70514389-70514389
4 COG4 NM_015386.3(COG4):c.2026T>C (p.Tyr676His) SNV Uncertain Significance
1341707 GRCh37: 16:70515747-70515747
GRCh38: 16:70481844-70481844
5 COG4 NM_015386.3(COG4):c.646C>T (p.Leu216=) SNV Benign
95699 rs3762171 GRCh37: 16:70546234-70546234
GRCh38: 16:70512331-70512331
6 COG4 NM_015386.3(COG4):c.2142G>A (p.Ser714=) SNV Benign
128810 rs11054 GRCh37: 16:70515355-70515355
GRCh38: 16:70481452-70481452
7 COG4 NM_015386.3(COG4):c.1482-25T>C SNV Benign
1179913 GRCh37: 16:70530359-70530359
GRCh38: 16:70496456-70496456
8 COG4 NM_015386.3(COG4):c.485C>T (p.Thr162Ile) SNV Benign
95697 rs3931036 GRCh37: 16:70548297-70548297
GRCh38: 16:70514394-70514394

UniProtKB/Swiss-Prot genetic disease variations for Saul-Wilson Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 COG4 p.Gly512Arg VAR_081564 rs1555575860

Expression for Saul-Wilson Syndrome

Search GEO for disease gene expression data for Saul-Wilson Syndrome.

Pathways for Saul-Wilson Syndrome

Pathways related to Saul-Wilson Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.98 VPS45 LMAN1 COG7 COG5 COG4 COG3
2
Show member pathways
12.63 COG1 COG3 COG4 COG5 COG7 VPS45
3
Show member pathways
12.55 GPC2 DCN CHST3 CHST14
4
Show member pathways
12.51 LMAN1 COG7 COG5 COG4 COG3 COG1
5
Show member pathways
12.38 GPC2 DCN CHST3 CHST14
6
Show member pathways
12.07 GPC2 DCN CHST3 CHST14
7 11.04 COG7 COG5 COG4 COG3 COG1
8 11.01 DCN CHST3
9 10.74 VPS45 COG7 COG5 COG4 COG3 COG1
10 10.66 CHST3 CHST14

GO Terms for Saul-Wilson Syndrome

Cellular components related to Saul-Wilson Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 10.1 VPS45 LMAN1 COG7 COG5 COG4 COG3
2 Golgi membrane GO:0000139 9.91 CHST14 CHST3 COG1 COG3 COG4 COG5
3 trans-Golgi network membrane GO:0032588 9.85 COG7 COG5 COG4 COG3 COG1
4 Golgi transport complex GO:0017119 9.32 COG7 COG5 COG4 COG3 COG1

Biological processes related to Saul-Wilson Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein transport GO:0015031 9.96 VPS45 LMAN1 COG7 COG5 COG4 COG3
2 Golgi organization GO:0007030 9.93 COG1 COG3 COG4 COG5 COG7 LMAN1
3 retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum GO:0006890 9.85 COG7 COG4 COG3
4 intra-Golgi vesicle-mediated transport GO:0006891 9.8 COG5 COG3 COG1
5 protein localization to organelle GO:0033365 9.71 COG7 COG3
6 glycosylation GO:0070085 9.65 COG7 COG5 COG4 COG3 COG1
7 retrograde transport, vesicle recycling within Golgi GO:0000301 9.32 COG7 COG5 COG4 COG3 COG1

Sources for Saul-Wilson Syndrome

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 24-Oct-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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