MCID: MLT072
MIFTS: 40

Multiple Synostoses Syndrome

Categories: Bone diseases, Ear diseases, Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Multiple Synostoses Syndrome

MalaCards integrated aliases for Multiple Synostoses Syndrome:

Name: Multiple Synostoses Syndrome 12 58 15
Symphalangism-Brachydactyly Syndrome 58 71
Deafness-Hermann Type Symphalangism Syndrome 58
Multiple Synostosis Syndrome 71
Facio-Audio-Symphalangism 58
Wl Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
multiple synostoses syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

Classifications:

Orphanet: 58  
Rare otorhinolaryngological diseases
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0050794
ICD10 via Orphanet 33 Q78.8
UMLS via Orphanet 72 C0175700 C0342282
Orphanet 58 ORPHA3237
UMLS 71 C0175700 C0342282

Summaries for Multiple Synostoses Syndrome

Disease Ontology : 12 A dysostosis that is characterized by premature joint ankylosis and has material basis in autosomal dominant inhertitance.

MalaCards based summary : Multiple Synostoses Syndrome, also known as symphalangism-brachydactyly syndrome, is related to multiple synostoses syndrome 2 and brachydactyly, and has symptoms including waddling gait An important gene associated with Multiple Synostoses Syndrome is GDF5 (Growth Differentiation Factor 5), and among its related pathways/superpathways are Akt Signaling and PAK Pathway. Affiliated tissues include bone and heart, and related phenotypes are joint stiffness and brachydactyly

Related Diseases for Multiple Synostoses Syndrome

Diseases in the Multiple Synostoses Syndrome family:

Multiple Synostoses Syndrome 1 Multiple Synostoses Syndrome 2
Multiple Synostoses Syndrome 3 Multiple Synostoses Syndrome 4

Diseases related to Multiple Synostoses Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 50)
# Related Disease Score Top Affiliating Genes
1 multiple synostoses syndrome 2 34.9 GDF5-AS1 GDF5
2 brachydactyly 30.4 NOG GDF5-AS1 GDF5 FGF9 BMPR1B BMPR1A
3 proximal symphalangism 29.6 YIPF2 PAEP NOG GDF6 GDF5 FGF9
4 multiple synostoses syndrome 3 12.8
5 multiple synostoses syndrome 4 12.8
6 multiple synostoses syndrome 1 12.8
7 photomyoclonus, diabetes mellitus, deafness, nephropathy, and cerebral dysfunction 11.5
8 symphalangism, proximal, 1b 10.5 GDF5-AS1 GDF5
9 leber congenital amaurosis 17 10.4 GDF6 GDF5
10 wildervanck syndrome 10.4
11 synovial chondromatosis 10.4 NOG FGF9
12 chromosome 10q23 deletion syndrome 10.4 BMPR1B BMPR1A
13 sugarman brachydactyly 10.4 NOG GDF5 BMPR1B
14 acromesomelic dysplasia, hunter-thompson type 10.4 GDF5 BMPR1B
15 acromesomelic dysplasia 10.3 GDF5-AS1 GDF5 BMPR1B
16 microphthalmia, isolated 4 10.3 PAEP GDF6 GDF5
17 pulmonary arterial hypertension associated with congenital heart disease 10.3 BMPR2 BMPR1B BMPR1A
18 branchiootic syndrome 1 10.3
19 lacrimoauriculodentodigital syndrome 10.3 GDF5 FGF9 FGF16
20 chondrodysplasia, grebe type 10.3 GDF5 BMPR1B
21 juvenile polyposis syndrome 10.3 NOG BMPR1B BMPR1A
22 submucous uterine fibroid 10.3 PAEP BMPR2
23 brachydactyly, type b2 10.3 YIPF2 NOG GDF5
24 brachydactyly, type b1 10.3 NOG GDF5
25 fibrodysplasia ossificans progressiva 10.3 NOG BMPR1A ACVR2A
26 bilateral renal aplasia 10.3 FGF9 FGF20
27 brachydactyly, type a1, c 10.3 NOG GDF6 GDF5-AS1 GDF5
28 tarsal-carpal coalition syndrome 10.3 YIPF2 NOG
29 deafness, autosomal recessive 71 10.3 FGF20 FGF16
30 brachydactyly, type a1, b 10.2 NOG GDF5 BMPR1B BMPR1A
31 chromosome 2q35 duplication syndrome 10.2 NOG GDF5 BMPR1B BMPR1A
32 heritable pulmonary arterial hypertension 10.2 BMPR2 BMPR1B
33 bone disease 10.2 NOG GDF6 GDF5 FGF9
34 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.2
35 acromesomelic dysplasia, maroteaux type 10.1 GDF5 BMPR1B
36 male infertility with azoospermia or oligozoospermia due to single gene mutation 10.1 SYCE1 NANOS1
37 fibular hypoplasia and complex brachydactyly 10.1 PAEP NOG GDF5-AS1 GDF5 BMPR1B
38 synostoses, tarsal, carpal, and digital 10.0 YIPF2 NOG GDF5 FGF9 BMPR1B
39 humeroradial synostosis 10.0
40 synostosis 10.0
41 otosclerosis 10.0
42 skeletal dysplasias 10.0
43 pectus carinatum 10.0
44 osteochondroma 10.0 FGF9 BMPR1B
45 brachydactyly, type a1 10.0 NOG GDF6 GDF5-AS1 GDF5 BMPR1B BMPR1A
46 d-bifunctional protein deficiency 9.8 LARS2 HSD17B4 CLPP
47 brachydactyly, type a2 9.8 PAEP NOG GDF6 GDF5 BMPR2 BMPR1B
48 perrault syndrome 9.7 LARS2 HSD17B4 EIF2B2 CLPP
49 46 xx gonadal dysgenesis 9.6 SYCE1 LARS2 HSD17B4 CLPP
50 premature ovarian failure 1 9.2 SYCE1 PAEP LARS2 HSD17B4 EIF2B2 CLPP

Graphical network of the top 20 diseases related to Multiple Synostoses Syndrome:



Diseases related to Multiple Synostoses Syndrome

Symptoms & Phenotypes for Multiple Synostoses Syndrome

Human phenotypes related to Multiple Synostoses Syndrome:

58 31 (show all 10)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint stiffness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001387
2 brachydactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001156
3 short palm 58 31 hallmark (90%) Very frequent (99-80%) HP:0004279
4 conductive hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000405
5 symphalangism affecting the phalanges of the hand 58 31 hallmark (90%) Very frequent (99-80%) HP:0009773
6 broad thumb 58 31 frequent (33%) Frequent (79-30%) HP:0011304
7 cone-shaped epiphysis 58 31 frequent (33%) Frequent (79-30%) HP:0010579
8 bilateral single transverse palmar creases 58 31 frequent (33%) Frequent (79-30%) HP:0007598
9 abnormality of the nail 58 31 occasional (7.5%) Occasional (29-5%) HP:0001597
10 facial asymmetry 58 31 occasional (7.5%) Occasional (29-5%) HP:0000324

UMLS symptoms related to Multiple Synostoses Syndrome:


waddling gait

GenomeRNAi Phenotypes related to Multiple Synostoses Syndrome according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased human cytomegalovirus (HCMV) strain AD169 replication GR00248-A 8.92 ACVR2A BMPR1A BMPR1B BMPR2

MGI Mouse Phenotypes related to Multiple Synostoses Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.97 ACVR2A BMPR1A BMPR1B BMPR2 CLPP FGF16
2 craniofacial MP:0005382 9.91 ACVR2A BMPR1A BMPR1B FGF16 FGF9 GDF6
3 reproductive system MP:0005389 9.85 ACVR2A BMPR1A BMPR1B CLPP FGF16 FGF9
4 hearing/vestibular/ear MP:0005377 9.8 BMPR1A FGF16 FGF20 FGF9 GDF6 HSD17B4
5 skeleton MP:0005390 9.65 ACVR2A BMPR1A BMPR1B BMPR2 CLPP FGF9
6 vision/eye MP:0005391 9.23 ACVR2A BMPR1A BMPR1B BMPR2 FGF9 GDF6

Drugs & Therapeutics for Multiple Synostoses Syndrome

Search Clinical Trials , NIH Clinical Center for Multiple Synostoses Syndrome

Genetic Tests for Multiple Synostoses Syndrome

Anatomical Context for Multiple Synostoses Syndrome

MalaCards organs/tissues related to Multiple Synostoses Syndrome:

40
Bone, Heart

Publications for Multiple Synostoses Syndrome

Articles related to Multiple Synostoses Syndrome:

(show all 30)
# Title Authors PMID Year
1
Facioaudiosymphalangism syndrome and growth acceleration associated with a heterozygous NOG mutation. 61 6
20503332 2010
2
Multiple synostoses syndrome is due to a missense mutation in exon 2 of FGF9 gene. 61 6
19589401 2009
3
Mutations of the NOG gene in individuals with proximal symphalangism and multiple synostosis syndrome. 61 6
11846737 2001
4
Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis. 61 6
10080184 1999
5
FGF9 mutation causes craniosynostosis along with multiple synostoses. 6
28730625 2017
6
Noggin suppression enhances in vitro osteogenesis and accelerates in vivo bone formation. 6
17609215 2007
7
GDF5 is a second locus for multiple-synostosis syndrome. 6
16532400 2006
8
Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. 6
16127465 2005
9
The facio-audio-symphalangism syndrome in a four generation family with a nonsense mutation in the NOG-gene. 6
15770128 2005
10
Symphalangism and its introduction into Hawaii: a pedigree. 6
3667255 1987
11
Conductive deafness, symphalangism, and facial abnormalities: the WL syndrome in a Japanese family. 6
6638061 1983
12
Modified French Osteotomy for Humeroradial Synostosis in a Child with Multiple Synostoses Syndrome: A Case Report. 61
31467654 2019
13
A Novel GDF6 Mutation in a Family with Multiple Synostoses Syndrome without Hearing Loss. 61
30733656 2019
14
Further delineation of the GDF6 related multiple synostoses syndrome. 61
29130651 2018
15
A point mutation in Fgf9 impedes joint interzone formation leading to multiple synostoses syndrome. 61
28169396 2017
16
A New Subtype of Multiple Synostoses Syndrome Is Caused by a Mutation in GDF6 That Decreases Its Sensitivity to Noggin and Enhances Its Potency as a BMP Signal. 61
26643732 2016
17
Novel NOG mutation in Japanese patients with stapes ankylosis with broad thumbs and toes. 61
26211601 2015
18
Improved bone defect healing by a superagonistic GDF5 variant derived from a patient with multiple synostoses syndrome. 61
25543012 2015
19
A mutation in the heparin-binding site of noggin as a novel mechanism of proximal symphalangism and conductive hearing loss. 61
24735539 2014
20
Multiple synostoses syndrome in three members of a family displaying a novel mutation in NOGGIN gene. 61
23732071 2013
21
Negative mutation screening of the NOG, BMPR1B, GDF5, and FGF9 genes indicates further genetic heterogeneity of the facioaudiosymphalangism syndrome. 61
22968293 2013
22
A GDF5 point mutation strikes twice--causing BDA1 and SYNS2. 61
24098149 2013
23
New insights into the molecular mechanism of multiple synostoses syndrome (SYNS): mutation within the GDF5 knuckle epitope causes noggin-resistance. 61
21976273 2012
24
A comprehensive review of reported heritable noggin-associated syndromes and proposed clinical utility of one broadly inclusive diagnostic term: NOG-related-symphalangism spectrum disorder (NOG-SSD). 61
21538686 2011
25
Otosclerosis or congenital stapes ankylosis? The diagnostic role of genetic analysis. 61
19471170 2009
26
Autosomal dominant stapes ankylosis with broad thumbs and toes, hyperopia, and skeletal anomalies is caused by heterozygous nonsense and frameshift mutations in NOG, the gene encoding noggin. 61
12089654 2002
27
Localization of a multiple synostoses-syndrome disease gene to chromosome 17q21-22. 61
9634519 1998
28
A case of multiple synostoses syndrome. 61
7401380 1980
29
The multiple synostoses syndrome. A plea for simplicity. 61
709952 1978
30
Symphalangism and brachydactyly syndrome: report of the WL symphalangism-brachydactyly syndrome: review of literature and classification. 61
4469994 1974

Variations for Multiple Synostoses Syndrome

Expression for Multiple Synostoses Syndrome

Search GEO for disease gene expression data for Multiple Synostoses Syndrome.

Pathways for Multiple Synostoses Syndrome

Pathways related to Multiple Synostoses Syndrome according to GeneCards Suite gene sharing:

(show all 13)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.17 GDF6 GDF5 FGF20 FGF16 BMPR2 BMPR1B
2
Show member pathways
13.07 GDF6 GDF5 FGF20 FGF16 BMPR2 BMPR1B
3
Show member pathways
12.28 NOG BMPR2 BMPR1A ACVR2A
4
Show member pathways
12.16 NOG BMPR2 BMPR1B BMPR1A ACVR2A
5
Show member pathways
12.03 GDF6 GDF5 FGF20 FGF16
6 11.85 BMPR2 BMPR1B BMPR1A ACVR2A
7 11.81 BMPR2 BMPR1B BMPR1A ACVR2A
8 11.74 GDF6 GDF5 BMPR2 BMPR1B BMPR1A
9 11.5 GDF6 GDF5 FGF20 FGF16
10
Show member pathways
11.37 FGF9 FGF20 FGF16
11
Show member pathways
11.21 NOG BMPR2 BMPR1B BMPR1A ACVR2A
12 11.14 NOG GDF6 GDF5 BMPR2 BMPR1B BMPR1A
13 10.78 BMPR2 BMPR1B BMPR1A

GO Terms for Multiple Synostoses Syndrome

Cellular components related to Multiple Synostoses Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 receptor complex GO:0043235 9.26 BMPR2 BMPR1B BMPR1A ACVR2A
2 HFE-transferrin receptor complex GO:1990712 8.62 BMPR1B BMPR1A

Biological processes related to Multiple Synostoses Syndrome according to GeneCards Suite gene sharing:

(show all 35)
# Name GO ID Score Top Affiliating Genes
1 cell-cell signaling GO:0007267 9.93 GDF5 FGF9 FGF20 FGF16
2 anterior/posterior pattern specification GO:0009952 9.84 BMPR2 BMPR1A ACVR2A
3 osteoblast differentiation GO:0001649 9.83 NOG HSD17B4 FGF9
4 transforming growth factor beta receptor signaling pathway GO:0007179 9.82 GDF5 BMPR2 BMPR1A
5 fibroblast growth factor receptor signaling pathway GO:0008543 9.81 FGF9 FGF20 FGF16
6 positive regulation of epithelial cell proliferation GO:0050679 9.79 NOG FGF9 BMPR1A
7 cartilage development GO:0051216 9.78 NOG GDF5 BMPR1B BMPR1A
8 outflow tract morphogenesis GO:0003151 9.77 NOG BMPR2 BMPR1A
9 embryonic skeletal system development GO:0048706 9.75 NOG FGF9 ACVR2A
10 dorsal/ventral pattern formation GO:0009953 9.74 NOG BMPR1B BMPR1A
11 cellular response to growth factor stimulus GO:0071363 9.73 BMPR2 BMPR1B BMPR1A ACVR2A
12 positive regulation of osteoblast differentiation GO:0045669 9.71 BMPR2 BMPR1B BMPR1A ACVR2A
13 chondrocyte differentiation GO:0002062 9.7 FGF9 BMPR1B BMPR1A
14 mesoderm formation GO:0001707 9.69 NOG BMPR2 BMPR1A
15 chondrocyte development GO:0002063 9.67 BMPR2 BMPR1B
16 positive regulation of chondrocyte differentiation GO:0032332 9.67 GDF6 GDF5 BMPR1B
17 proteoglycan biosynthetic process GO:0030166 9.66 BMPR2 BMPR1B
18 endocardial cushion morphogenesis GO:0003203 9.65 NOG BMPR1A
19 positive regulation of cartilage development GO:0061036 9.65 BMPR2 BMPR1B
20 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0010862 9.65 GDF6 GDF5 BMPR2 BMPR1A ACVR2A
21 hindlimb morphogenesis GO:0035137 9.64 GDF5 BMPR1A
22 activin receptor signaling pathway GO:0032924 9.63 GDF6 BMPR2 ACVR2A
23 mitral valve morphogenesis GO:0003183 9.62 BMPR2 BMPR1A
24 positive regulation of bone mineralization GO:0030501 9.62 BMPR2 BMPR1B BMPR1A ACVR2A
25 regulation of cardiac muscle cell proliferation GO:0060043 9.61 FGF20 BMPR1A
26 positive regulation of activin receptor signaling pathway GO:0032927 9.61 FGF9 ACVR2A
27 ventricular compact myocardium morphogenesis GO:0003223 9.6 NOG BMPR1A
28 BMP signaling pathway involved in heart development GO:0061312 9.58 NOG BMPR1A
29 negative regulation of chondrocyte proliferation GO:1902731 9.56 BMPR2 BMPR1B
30 endochondral bone morphogenesis GO:0060350 9.55 BMPR2 BMPR1B
31 cellular response to BMP stimulus GO:0071773 9.55 NOG BMPR2 BMPR1B BMPR1A ACVR2A
32 tricuspid valve morphogenesis GO:0003186 9.54 BMPR2 BMPR1A
33 pharyngeal arch artery morphogenesis GO:0061626 9.54 NOG BMPR2 BMPR1A
34 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007178 9.35 GDF5 BMPR2 BMPR1B BMPR1A ACVR2A
35 BMP signaling pathway GO:0030509 9.17 NOG GDF6 GDF5 BMPR2 BMPR1B BMPR1A

Molecular functions related to Multiple Synostoses Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 growth factor activity GO:0008083 9.55 GDF6 GDF5 FGF9 FGF20 FGF16
2 fibroblast growth factor receptor binding GO:0005104 9.43 FGF9 FGF20 FGF16
3 BMP binding GO:0036122 9.37 GDF5 BMPR2
4 transforming growth factor beta receptor activity, type I GO:0005025 9.32 BMPR1B BMPR1A
5 BMP receptor activity GO:0098821 9.13 BMPR2 BMPR1A ACVR2A
6 transmembrane receptor protein serine/threonine kinase activity GO:0004675 8.92 BMPR2 BMPR1B BMPR1A ACVR2A

Sources for Multiple Synostoses Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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