SYNS1
MCID: MLT059
MIFTS: 32

Multiple Synostoses Syndrome 1 (SYNS1)

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

Aliases & Classifications for Multiple Synostoses Syndrome 1

MalaCards integrated aliases for Multiple Synostoses Syndrome 1:

Name: Multiple Synostoses Syndrome 1 57 20 72
Symphalangism-Brachydactyly Syndrome 57 72 29 6 70
Syns1 57 20 72 54
Deafness-Symphalangism Syndrome of Herrmann 57 20 72
Facioaudiosymphalangism Syndrome 57 20 72
Wl Syndrome 57 20 72
Synostoses Multiple with Brachydactyly 20 72
Synostoses, Multiple, with Brachydactyly 57
Syndrome, Synostoses, Multiple, Type 1 39
Symphalangism Brachydactyly Syndrome 20

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
waddling gait
allelic to proximal symphalangism , stapes ankylosis syndrome without symphalangism , and tarsal-carpal coalition syndrome

Inheritance:
autosomal dominant


HPO:

31
multiple synostoses syndrome 1:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Multiple Synostoses Syndrome 1

OMIM® : 57 Multiple synostoses syndrome is characterized by multiple joint fusions, usually commencing in the hands, conductive deafness, and characteristic facial features, including a broad, tubular-shaped nose and a thin upper vermilion. Other features include brachydactyly, hypoplastic or absent middle phalanges, radial head dislocation, and pectus carinatum (summary by Takahashi et al., 2001). (186500) (Updated 05-Apr-2021)

MalaCards based summary : Multiple Synostoses Syndrome 1, also known as symphalangism-brachydactyly syndrome, is related to multiple synostoses syndrome and photomyoclonus, diabetes mellitus, deafness, nephropathy, and cerebral dysfunction, and has symptoms including waddling gait An important gene associated with Multiple Synostoses Syndrome 1 is NOG (Noggin). Affiliated tissues include bone, and related phenotypes are abnormal vertebral morphology and strabismus

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 3237 Definition Multiple synostoses syndrome (MSS) is a rare developmental bone disorder characterized by proximal symphalangism of the fingers and/or toes often associated with fusion of carpal and tarsal, humeroradial, and cervical spine joints.

UniProtKB/Swiss-Prot : 72 Multiple synostoses syndrome 1: 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 1

Graphical network of the top 20 diseases related to Multiple Synostoses Syndrome 1:



Diseases related to Multiple Synostoses Syndrome 1

Symptoms & Phenotypes for Multiple Synostoses Syndrome 1

Human phenotypes related to Multiple Synostoses Syndrome 1:

31 (show all 38)
# Description HPO Frequency HPO Source Accession
1 abnormal vertebral morphology 31 HP:0003468
2 strabismus 31 HP:0000486
3 short sternum 31 HP:0000879
4 cubitus valgus 31 HP:0002967
5 pectus excavatum 31 HP:0000767
6 waddling gait 31 HP:0002515
7 narrow face 31 HP:0000275
8 brachydactyly 31 HP:0001156
9 thin upper lip vermilion 31 HP:0000219
10 spinal canal stenosis 31 HP:0003416
11 short philtrum 31 HP:0000322
12 short hallux 31 HP:0010109
13 cutaneous finger syndactyly 31 HP:0010554
14 underdeveloped nasal alae 31 HP:0000430
15 short foot 31 HP:0001773
16 tarsal synostosis 31 HP:0008368
17 aplastic/hypoplastic toenail 31 HP:0010624
18 single transverse palmar crease 31 HP:0000954
19 short lower limbs 31 HP:0006385
20 thick upper lip vermilion 31 HP:0000215
21 dislocated radial head 31 HP:0003083
22 radial deviation of finger 31 HP:0009466
23 anonychia 31 HP:0001798
24 short humerus 31 HP:0005792
25 2-3 toe syndactyly 31 HP:0004691
26 stapes ankylosis 31 HP:0000381
27 carpal synostosis 31 HP:0009702
28 lower limb undergrowth 31 HP:0009816
29 aplasia/hypoplasia of the middle phalanges of the hand 31 HP:0009843
30 clinodactyly 31 HP:0030084
31 absent distal interphalangeal creases 31 HP:0001032
32 absent distal phalanges 31 HP:0005807
33 hypoplastic nasal septum 31 HP:0005104
34 progressive conductive hearing impairment 31 HP:0008607
35 enlargement of the costochondral junction 31 HP:0000920
36 proximal symphalangism of hands 31 HP:0006152
37 fusion of midphalangeal joints 31 HP:0006187
38 hypoplastic spinal processes 31 HP:0008460

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
strabismus

Skeletal Limbs:
cubitus valgus
dislocated radial head
short legs
short upper arms
limited forearm pronation/supination

Skeletal Hands:
brachydactyly
clinodactyly
fusion of midphalangeal joints
proximal symphalangism (2,3,4)
cutaneous syndactyly (2,3,4)
more
Head And Neck Ears:
stapes ankylosis
progressive conductive deafness

Head And Neck Nose:
hypoplastic nasal septum
hypoplastic alae nasi
hemicylindrical nose

Skin Nails Hair Skin:
single palmar creases
absence of skin creases over proximal interphalangeal (pip) joints
absence of skin creases over distal interphalangeal (dip) joints

Chest Ribs Sternum Clavicles And Scapulae:
short sternum
pectus excavatum
anteriorly positioned shoulders
prominent costochondral junction

Head And Neck Face:
narrow face
short philtrum

Skeletal Spine:
spinal canal stenosis
vertebral anomalies
hypoplastic spinal processes (cervical vertebrae)

Skeletal Feet:
absent distal phalanges
short feet
short halluces
tarsal fusions
cutaneous 2,3 toe syndactyly
more
Head And Neck Mouth:
thin vermilion border of upper lip

Skin Nails Hair Nails:
aplastic/hypoplastic fingernails
aplastic/hypoplastic toenails

Clinical features from OMIM®:

186500 (Updated 05-Apr-2021)

UMLS symptoms related to Multiple Synostoses Syndrome 1:


waddling gait

Drugs & Therapeutics for Multiple Synostoses Syndrome 1

Search Clinical Trials , NIH Clinical Center for Multiple Synostoses Syndrome 1

Genetic Tests for Multiple Synostoses Syndrome 1

Genetic tests related to Multiple Synostoses Syndrome 1:

# Genetic test Affiliating Genes
1 Symphalangism-Brachydactyly Syndrome 29 NOG

Anatomical Context for Multiple Synostoses Syndrome 1

MalaCards organs/tissues related to Multiple Synostoses Syndrome 1:

40
Bone

Publications for Multiple Synostoses Syndrome 1

Articles related to Multiple Synostoses Syndrome 1:

(show all 27)
# Title Authors PMID Year
1
Facioaudiosymphalangism syndrome and growth acceleration associated with a heterozygous NOG mutation. 6 57 54
20503332 2010
2
Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis. 6 57 61
10080184 1999
3
Noggin suppression enhances in vitro osteogenesis and accelerates in vivo bone formation. 6 57
17609215 2007
4
GDF5 is a second locus for multiple-synostosis syndrome. 6 57
16532400 2006
5
The facio-audio-symphalangism syndrome in a four generation family with a nonsense mutation in the NOG-gene. 6 57
15770128 2005
6
Mutations of the NOG gene in individuals with proximal symphalangism and multiple synostosis syndrome. 57 6
11846737 2001
7
Symphalangism and its introduction into Hawaii: a pedigree. 57 6
3667255 1987
8
Conductive deafness, symphalangism, and facial abnormalities: the WL syndrome in a Japanese family. 6 57
6638061 1983
9
A new subtype of brachydactyly type B caused by point mutations in the bone morphogenetic protein antagonist NOGGIN. 57
17668388 2007
10
Herrmann multiple synostosis syndrome with neurological complications caused by spinal canal stenosis. 57
11078560 2000
11
Localization of a multiple synostoses-syndrome disease gene to chromosome 17q21-22. 57
9634519 1998
12
The facio-audio-symphalangism syndrome: report of a case and review of the literature. 57
4028502 1985
13
Multiple synostosis syndrome: study of a large Brazilian kindred. 57
6465200 1984
14
[Multiple synostosis disease]. 57
4648959 1972
15
[Dominant hereditary bilateral dysplasia and synostosis of the elbow joint, with symmetrical brachymesophalangy and brachymetacarpy as well as synostoses in the finger, carpal and tarsal region]. 57
5986056 1966
16
Hereditary Anchylosis of the Proximal Phalan-Geal Joints (Symphalangism). 57
17245852 1916
17
P35S mutation in the NOG gene associated with Teunissen-Cremers syndrome and features of multiple NOG joint-fusion syndromes. 54 61
18440889 2008
18
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. 54 61
12089654 2002
19
Human disease-causing NOG missense mutations: effects on noggin secretion, dimer formation, and bone morphogenetic protein binding. 61 54
11562478 2001
20
Multiple synostoses syndrome: Clinical report and retrospective analysis. 61
32259393 2020
21
Further delineation of facioaudiosymphalangism syndrome: Description of a family with a novel NOG mutation and without hearing loss. 61
26994744 2016
22
Novel NOG mutation in Japanese patients with stapes ankylosis with broad thumbs and toes. 61
26211601 2015
23
Identification of two novel mutations in the NOG gene associated with congenital stapes ankylosis and symphalangism. 61
25391606 2015
24
Mutations in the NOG gene are commonly found in congenital stapes ankylosis with symphalangism, but not in otosclerosis. 61
22288654 2012
25
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
26
Congenital conductive hearing loss and multiple synostosis syndrome with analysis of temporal bone CT scan findings. 61
20870298 2010
27
Stapes ankylosis in a family with a novel NOG mutation: otologic features of the facioaudiosymphalangism syndrome. 54
16151340 2005

Variations for Multiple Synostoses Syndrome 1

ClinVar genetic disease variations for Multiple Synostoses Syndrome 1:

6 (show all 28)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NOG NM_005450.5(NOG):c.649T>G (p.Trp217Gly) SNV Pathogenic 6693 rs104894603 GRCh37: 17:54672233-54672233
GRCh38: 17:56594872-56594872
2 NOG NOG, 1-BP DEL Deletion Pathogenic 6701 GRCh37:
GRCh38:
3 NOG NM_005450.5(NOG):c.614G>A (p.Trp205Ter) SNV Pathogenic 6706 rs1567745119 GRCh37: 17:54672198-54672198
GRCh38: 17:56594837-56594837
4 NOG NM_005450.5(NOG):c.615G>C (p.Trp205Cys) SNV Pathogenic 6707 rs104894615 GRCh37: 17:54672199-54672199
GRCh38: 17:56594838-56594838
5 NOG NM_005450.5(NOG):c.696C>G (p.Cys232Trp) SNV Pathogenic 30290 rs387906844 GRCh37: 17:54672280-54672280
GRCh38: 17:56594919-56594919
6 NOG NM_005450.6(NOG):c.64dup (p.Ala22fs) Duplication Pathogenic 827845 rs1597919829 GRCh37: 17:54671645-54671646
GRCh38: 17:56594284-56594285
7 NOG NM_005450.5(NOG):c.611G>A (p.Arg204Gln) SNV Likely pathogenic 375295 rs104894610 GRCh37: 17:54672195-54672195
GRCh38: 17:56594834-56594834
8 FGF9 NM_002010.3(FGF9):c.-37dup Duplication Uncertain significance 311420 rs752566182 GRCh37: 13:22246014-22246015
GRCh38: 13:21671875-21671876
9 FGF9 NM_002010.3(FGF9):c.*435C>T SNV Uncertain significance 311443 rs886050052 GRCh37: 13:22276009-22276009
GRCh38: 13:21701870-21701870
10 FGF9 NM_002010.3(FGF9):c.*2210del Deletion Uncertain significance 311465 rs577984328 GRCh37: 13:22277775-22277775
GRCh38: 13:21703636-21703636
11 FGF9 NM_002010.3(FGF9):c.*2463dup Duplication Uncertain significance 311468 rs757466207 GRCh37: 13:22278024-22278025
GRCh38: 13:21703885-21703886
12 FGF9 NM_002010.3(FGF9):c.*479_*482CTTA[1] Microsatellite Uncertain significance 311445 rs886050053 GRCh37: 13:22276053-22276056
GRCh38: 13:21701914-21701917
13 FGF9 NM_002010.3(FGF9):c.*274_*275del Deletion Uncertain significance 311434 rs886050049 GRCh37: 13:22275847-22275848
GRCh38: 13:21701708-21701709
14 FGF9 NM_002010.3(FGF9):c.*276_*277GT[14] Microsatellite Uncertain significance 311437 rs61706549 GRCh37: 13:22275849-22275850
GRCh38: 13:21701710-21701711
15 FGF9 NM_002010.3(FGF9):c.-335del Deletion Uncertain significance 311411 rs886050042 GRCh37: 13:22245710-22245710
GRCh38: 13:21671571-21671571
16 FGF9 NM_002010.3(FGF9):c.*274_*279del Deletion Uncertain significance 311432 rs886050047 GRCh37: 13:22275843-22275848
GRCh38: 13:21701704-21701709
17 FGF9 NM_002010.3(FGF9):c.*276_*277GT[16] Microsatellite Uncertain significance 311435 rs61706549 GRCh37: 13:22275848-22275849
GRCh38: 13:21701709-21701710
18 FGF9 NM_002010.3(FGF9):c.*1507A>G SNV Uncertain significance 311458 rs886050057 GRCh37: 13:22277081-22277081
GRCh38: 13:21702942-21702942
19 FGF9 NM_002010.3(FGF9):c.-116dup Duplication Uncertain significance 311418 rs1555223891 GRCh37: 13:22245935-22245936
GRCh38: 13:21671796-21671797
20 FGF9 NM_002010.3(FGF9):c.-585dup Duplication Uncertain significance 311407 rs886050040 GRCh37: 13:22245461-22245462
GRCh38: 13:21671322-21671323
21 LOC109461476 , GDF5 NM_000557.5(GDF5):c.-30C>A SNV Uncertain significance 338324 rs375024998 GRCh37: 20:34025738-34025738
GRCh38: 20:35437958-35437958
22 FGF9 NM_002010.3(FGF9):c.*276_*277GT[19] Microsatellite Uncertain significance 311436 rs61706549 GRCh37: 13:22275848-22275849
GRCh38: 13:21701709-21701710
23 FGF9 NM_002010.3(FGF9):c.*266_*267GT[5] Microsatellite Uncertain significance 311430 rs761639029 GRCh37: 13:22275839-22275840
GRCh38: 13:21701700-21701701
24 FGF9 NM_002010.3(FGF9):c.*274_*277del Deletion Uncertain significance 311433 rs201279299 GRCh37: 13:22275845-22275848
GRCh38: 13:21701706-21701709
25 FGF9 NM_002010.3(FGF9):c.-118_-117insC Insertion Likely benign 311417 rs1555223896 GRCh37: 13:22245934-22245935
GRCh38: 13:21671795-21671796
26 FGF9 NM_002010.3(FGF9):c.*2497del Deletion Likely benign 311469 rs148832636 GRCh37: 13:22278070-22278070
GRCh38: 13:21703931-21703931
27 FGF9 NM_002010.3(FGF9):c.-118_-117dup Duplication Benign 311416 rs10624265 GRCh37: 13:22245927-22245928
GRCh38: 13:21671788-21671789
28 FGF9 NM_002010.3(FGF9):c.-117dup Duplication Benign 311415 rs10624265 GRCh37: 13:22245927-22245928
GRCh38: 13:21671788-21671789

UniProtKB/Swiss-Prot genetic disease variations for Multiple Synostoses Syndrome 1:

72
# Symbol AA change Variation ID SNP ID
1 NOG p.Trp217Gly VAR_011363 rs104894603
2 NOG p.Cys232Trp VAR_064541 rs387906844

Expression for Multiple Synostoses Syndrome 1

Search GEO for disease gene expression data for Multiple Synostoses Syndrome 1.

Pathways for Multiple Synostoses Syndrome 1

GO Terms for Multiple Synostoses Syndrome 1

Sources for Multiple Synostoses Syndrome 1

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