SYNS2
MCID: MLT060
MIFTS: 28

Multiple Synostoses Syndrome 2 (SYNS2)

Categories: Bone diseases, Ear diseases, Fetal diseases, Genetic diseases, Rare diseases, Smell/Taste diseases
Data Licensing
For inquiries, contact:

Aliases & Classifications for Multiple Synostoses Syndrome 2

MalaCards integrated aliases for Multiple Synostoses Syndrome 2:

Name: Multiple Synostoses Syndrome 2 57 19 73 28 5 71
Syns2 57 19 73

Characteristics:


Inheritance:

Autosomal dominant 57

Classifications:



External Ids:

OMIM® 57 610017
OMIM Phenotypic Series 57 PS186500
MeSH 43 D013580
MedGen 40 C1832708
UMLS 71 C1832708

Summaries for Multiple Synostoses Syndrome 2

OMIM®: 57 Multiple synostoses syndrome-2 (SYNS2) is an autosomal dominant disorder characterized by progressive joint fusions of the fingers, wrists, ankles, and cervical spine; characteristic facies, including a broad hemicylindrical nose; and progressive conductive hearing loss (summary by Dawson et al., 2006). For a general phenotypic description and a discussion of genetic heterogeneity of multiple synostoses syndrome, see SYNS1 (186500). (610017) (Updated 08-Dec-2022)

MalaCards based summary: Multiple Synostoses Syndrome 2, also known as syns2, is related to brachydactyly, type a1 and contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a. An important gene associated with Multiple Synostoses Syndrome 2 is GDF5 (Growth Differentiation Factor 5). Affiliated tissues include bone, and related phenotypes are talipes equinovarus and brachydactyly

GARD: 19 Multiple synostoses syndrome-2 (SYNS2) is an autosomal dominant disorder characterized by progressive joint fusions of the fingers, wrists, ankles, and cervical spine; characteristic facies, including a broad hemicylindrical nose; and progressive conductive hearing loss (summary by Dawson et al., 2006).For a general phenotypic description and a discussion of genetic heterogeneity of multiple synostoses syndrome, see SYNS1 (186500).

UniProtKB/Swiss-Prot: 73 A bone disease characterized by multiple progressive joint fusions that commonly involve proximal interphalangeal, tarsal-carpal, humeroradial and cervical spine joints. Additional features can include progressive conductive deafness and facial dysmorphism.

Related Diseases for Multiple Synostoses Syndrome 2

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 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 brachydactyly, type a1 10.0
2 contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a 10.0
3 brachydactyly 10.0
4 multiple synostoses syndrome 10.0
5 symphalangism, proximal, 1b 9.7 GDF5-AS1 GDF5
6 brachydactyly, type a1, c 9.7 GDF5-AS1 GDF5
7 acromesomelic dysplasia 2a 9.7 GDF5-AS1 GDF5
8 acromesomelic dysplasia 2b 9.6 GDF5-AS1 GDF5
9 brachydactyly, type c 9.6 GDF5-AS1 GDF5
10 brachydactyly, type a2 9.5 GDF5-AS1 GDF5

Graphical network of the top 20 diseases related to Multiple Synostoses Syndrome 2:



Diseases related to Multiple Synostoses Syndrome 2

Symptoms & Phenotypes for Multiple Synostoses Syndrome 2

Human phenotypes related to Multiple Synostoses Syndrome 2:

30 (show all 9)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 talipes equinovarus 30 Occasional (7.5%) HP:0001762
2 brachydactyly 30 HP:0001156
3 vertebral fusion 30 HP:0002948
4 wide nose 30 HP:0000445
5 carpal synostosis 30 HP:0009702
6 humeroradial synostosis 30 HP:0003041
7 finger symphalangism 30 HP:0009700
8 proximal symphalangism 30 HP:0100264
9 tarsal synostosis 30 HP:0008368

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Skeletal Hands:
brachydactyly
proximal symphalangism
carpal fusions
carpal coalition
progressive symphalangism

Skeletal Feet:
talipes equinovarus (in some patients)
tarsal fusions
tarsal coalition

Head And Neck Nose:
broad hemicyclindrical nose

Skeletal Limbs:
humeroradial synostosis

Skeletal Spine:
vertebral fusions

Clinical features from OMIM®:

610017 (Updated 08-Dec-2022)

Drugs & Therapeutics for Multiple Synostoses Syndrome 2

Search Clinical Trials, NIH Clinical Center for Multiple Synostoses Syndrome 2

Genetic Tests for Multiple Synostoses Syndrome 2

Genetic tests related to Multiple Synostoses Syndrome 2:

# Genetic test Affiliating Genes
1 Multiple Synostoses Syndrome 2 28 GDF5

Anatomical Context for Multiple Synostoses Syndrome 2

Organs/tissues related to Multiple Synostoses Syndrome 2:

MalaCards : Bone

Publications for Multiple Synostoses Syndrome 2

Articles related to Multiple Synostoses Syndrome 2:

# Title Authors PMID Year
1
GDF5 is a second locus for multiple-synostosis syndrome. 57 5
16532400 2006
2
Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. 5
16127465 2005
3
Improved bone defect healing by a superagonistic GDF5 variant derived from a patient with multiple synostoses syndrome. 62
25543012 2015
4
A GDF5 point mutation strikes twice--causing BDA1 and SYNS2. 62
24098149 2013

Variations for Multiple Synostoses Syndrome 2

ClinVar genetic disease variations for Multiple Synostoses Syndrome 2:

5 (show all 41)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.1313G>T (p.Arg438Leu) SNV Pathogenic
8386 rs74315388 GRCh37: 20:34021900-34021900
GRCh38: 20:35434102-35434102
2 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.1424G>A (p.Ser475Asn) SNV Pathogenic
8388 rs121909347 GRCh37: 20:34021789-34021789
GRCh38: 20:35433991-35433991
3 LOC109461476, GDF5 NM_000557.5(GDF5):c.-220C>T SNV Uncertain Significance
338327 rs886056643 GRCh37: 20:34025928-34025928
GRCh38: 20:35438148-35438148
4 GDF5 NM_000557.5(GDF5):c.226G>T (p.Ala76Ser) SNV Uncertain Significance
895672 rs768978933 GRCh37: 20:34025483-34025483
GRCh38: 20:35437703-35437703
5 LOC109461476, GDF5 NM_000557.5(GDF5):c.-97T>C SNV Uncertain Significance
895743 rs960967052 GRCh37: 20:34025805-34025805
GRCh38: 20:35438025-35438025
6 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.*166G>A SNV Uncertain Significance
338315 rs569761315 GRCh37: 20:34021541-34021541
GRCh38: 20:35433743-35433743
7 GDF5 NM_000557.5(GDF5):c.506C>A (p.Pro169His) SNV Uncertain Significance
895610 rs2062477372 GRCh37: 20:34025203-34025203
GRCh38: 20:35437423-35437423
8 GDF5 NM_000557.5(GDF5):c.182G>A (p.Gly61Glu) SNV Uncertain Significance
897084 rs1601074882 GRCh37: 20:34025527-34025527
GRCh38: 20:35437747-35437747
9 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.1374C>G (p.Pro458=) SNV Uncertain Significance
896867 rs776415223 GRCh37: 20:34021839-34021839
GRCh38: 20:35434041-35434041
10 GDF5 NM_000557.5(GDF5):c.483G>A (p.Pro161=) SNV Uncertain Significance
897014 rs752789551 GRCh37: 20:34025226-34025226
GRCh38: 20:35437446-35437446
11 GDF5 NM_000557.5(GDF5):c.57G>T (p.Leu19=) SNV Uncertain Significance
897561 rs746980493 GRCh37: 20:34025652-34025652
GRCh38: 20:35437872-35437872
12 GDF5 NM_000557.5(GDF5):c.25T>C (p.Phe9Leu) SNV Uncertain Significance
595155 rs373973964 GRCh37: 20:34025684-34025684
GRCh38: 20:35437904-35437904
13 LOC109461476, GDF5 NM_000557.5(GDF5):c.-236G>A SNV Uncertain Significance
898778 rs1190526111 GRCh37: 20:34025944-34025944
GRCh38: 20:35438164-35438164
14 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.1067A>G (p.Asn356Ser) SNV Uncertain Significance
895535 rs367914931 GRCh37: 20:34022146-34022146
GRCh38: 20:35434348-35434348
15 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.1104C>T (p.Thr368=) SNV Likely Benign
338317 rs748907807 GRCh37: 20:34022109-34022109
GRCh38: 20:35434311-35434311
16 GDF5 NM_000557.5(GDF5):c.206C>G (p.Ala69Gly) SNV Likely Benign
895673 rs542574339 GRCh37: 20:34025503-34025503
GRCh38: 20:35437723-35437723
17 GDF5 NM_000557.5(GDF5):c.168C>A (p.Asn56Lys) SNV Likely Benign
338323 rs199666386 GRCh37: 20:34025541-34025541
GRCh38: 20:35437761-35437761
18 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.*259G>C SNV Benign
895466 rs150833046 GRCh37: 20:34021448-34021448
GRCh38: 20:35433650-35433650
19 GDF5 NM_000557.5(GDF5):c.631+6G>A SNV Benign
895609 rs768697784 GRCh37: 20:34025072-34025072
GRCh38: 20:35437292-35437292
20 LOC109461476, GDF5 NM_000557.5(GDF5):c.-134C>G SNV Benign
896024 rs144924248 GRCh37: 20:34025842-34025842
GRCh38: 20:35438062-35438062
21 LOC109461476, GDF5 NM_000557.5(GDF5):c.-39C>T SNV Benign
338325 rs149907722 GRCh37: 20:34025747-34025747
GRCh38: 20:35437967-35437967
22 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.*387T>C SNV Benign
338312 rs553655935 GRCh37: 20:34021320-34021320
GRCh38: 20:35433522-35433522
23 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.*335A>C SNV Benign
338313 rs73611720 GRCh37: 20:34021372-34021372
GRCh38: 20:35433574-35433574
24 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.*389C>T SNV Benign
338311 rs535023630 GRCh37: 20:34021318-34021318
GRCh38: 20:35433520-35433520
25 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.*193G>T SNV Benign
338314 rs114832948 GRCh37: 20:34021514-34021514
GRCh38: 20:35433716-35433716
26 LOC109461476, GDF5 NM_000557.5(GDF5):c.-48= SNV Benign
256712 rs143384 GRCh37: 20:34025756-34025756
GRCh38: 20:35437976-35437976
27 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.*520T>C SNV Benign
338309 rs188252641 GRCh37: 20:34021187-34021187
GRCh38: 20:35433389-35433389
28 LOC109461476, GDF5 NM_000557.5(GDF5):c.-135G>A SNV Benign
338326 rs73094730 GRCh37: 20:34025843-34025843
GRCh38: 20:35438063-35438063
29 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.*425T>C SNV Benign
338310 rs56366915 GRCh37: 20:34021282-34021282
GRCh38: 20:35433484-35433484
30 GDF5 NM_000557.5(GDF5):c.462C>A (p.Pro154=) SNV Benign
193119 rs150686636 GRCh37: 20:34025247-34025247
GRCh38: 20:35437467-35437467
31 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.*468G>A SNV Benign
895403 rs79051206 GRCh37: 20:34021239-34021239
GRCh38: 20:35433441-35433441
32 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.855C>T (p.Gly285=) SNV Benign
338320 rs149593773 GRCh37: 20:34022358-34022358
GRCh38: 20:35434560-35434560
33 GDF5 NM_000557.5(GDF5):c.652A>C (p.Arg218=) SNV Benign
284616 rs116467702 GRCh37: 20:34022561-34022561
GRCh38: 20:35434763-35434763
34 GDF5 NM_000557.5(GDF5):c.349G>T (p.Ala117Ser) SNV Benign
338322 rs151149144 GRCh37: 20:34025360-34025360
GRCh38: 20:35437580-35437580
35 LOC109461476, GDF5 NM_000557.5(GDF5):c.-275= SNV Benign
8390 rs143383 GRCh37: 20:34025983-34025983
GRCh38: 20:35438203-35438203
36 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.1128G>T (p.Gln376His) SNV Benign
338316 rs138130158 GRCh37: 20:34022085-34022085
GRCh38: 20:35434287-35434287
37 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.1017= (p.Lys339=) SNV Benign
256713 rs224330 GRCh37: 20:34022196-34022196
GRCh38: 20:35434398-35434398
38 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.826= (p.Ala276=) SNV Benign
256716 rs224331 GRCh37: 20:34022387-34022387
GRCh38: 20:35434589-35434589
39 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.953G>C (p.Arg318Pro) SNV Benign
338319 rs201590447 GRCh37: 20:34022260-34022260
GRCh38: 20:35434462-35434462
40 GDF5 NM_000557.5(GDF5):c.497C>A (p.Pro166His) SNV Benign
338321 rs61754581 GRCh37: 20:34025212-34025212
GRCh38: 20:35437432-35437432
41 GDF5-AS1, GDF5 NM_000557.5(GDF5):c.1000C>G (p.Arg334Gly) SNV Benign
338318 rs140895068 GRCh37: 20:34022213-34022213
GRCh38: 20:35434415-35434415

UniProtKB/Swiss-Prot genetic disease variations for Multiple Synostoses Syndrome 2:

73
# Symbol AA change Variation ID SNP ID
1 GDF5 p.Leu441Pro VAR_017408 rs28936683
2 GDF5 p.Arg438Leu VAR_026545 rs74315388
3 GDF5 p.Ser475Asn VAR_037982 rs121909347
4 GDF5 p.Trp414Arg VAR_073141
5 GDF5 p.Asn445Lys VAR_073142
6 GDF5 p.Asn445Thr VAR_073143

Expression for Multiple Synostoses Syndrome 2

Search GEO for disease gene expression data for Multiple Synostoses Syndrome 2.

Pathways for Multiple Synostoses Syndrome 2

GO Terms for Multiple Synostoses Syndrome 2

Sources for Multiple Synostoses Syndrome 2

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 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....