SPD
MCID: SYN012
MIFTS: 38

Synpolydactyly (SPD)

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

Aliases & Classifications for Synpolydactyly

MalaCards integrated aliases for Synpolydactyly:

Name: Synpolydactyly 12 73 20 58 36 54 15
Syndactyly Type 2 12 73 20 58
Syndactyly, Type 2 44 70
Spd 20

Characteristics:

Orphanet epidemiological data:

58
syndactyly type 2
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0060242
KEGG 36 H00459
MeSH 44 C538153
NCIt 50 C75005
SNOMED-CT 67 715724002
MESH via Orphanet 45 C538153
ICD10 via Orphanet 33 Q70.0 Q70.2
UMLS via Orphanet 71 C2699746
Orphanet 58 ORPHA93403
UMLS 70 C2699746

Summaries for Synpolydactyly

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 93403 Definition Syndactyly type 2 or synpolydactyly (SPD) is a rare congenital distal limb malformation characterized by the combination of syndactyly and polydactyly. Epidemiology The prevalence is unknown. Clinical description In most cases, SPD affects the 3rd and 4th fingers and the 4th and 5th toes, bilaterally. Additional features include 5th finger clinodactyly, camptodactyly and/or brachydactyly. Etiology Three loci have been identified: SPD1( HOXD13 gene, 2q31 locus), SPD2 ( FBLN1 gene; 22q13.31) and SPD3 (14q11.2-q12). Genetic counseling SPD is inherited in an autosomal dominant manner.

MalaCards based summary : Synpolydactyly, also known as syndactyly type 2, is related to synpolydactyly 1 and brachydactyly-syndactyly syndrome. An important gene associated with Synpolydactyly is HOXD13 (Homeobox D13). Related phenotypes are sandal gap and clinodactyly of the 5th finger

Disease Ontology : 12 A syndactyly characterized by an increased number of digits; often a result of a mutation in the HOXD13 gene.

KEGG : 36 Synpolydactyly (SPD) is a dominantly inherited congenital limb malformation showing digit duplication and webbing of third and fourth fingers. Mutation in HOXD13 induces synpolydactyly. Synpolydactyly 2 is associated with metacarpal and metatarsal synostoses. Synpolydactyly 2 is very rare and caused by mutations in FBLN1.

Wikipedia : 73 Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some... more...

Related Diseases for Synpolydactyly

Diseases in the Synpolydactyly family:

Synpolydactyly 1 Synpolydactyly 2
Synpolydactyly 3

Diseases related to Synpolydactyly via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 123)
# Related Disease Score Top Affiliating Genes
1 synpolydactyly 1 32.9 HOXD13 CHST11
2 brachydactyly-syndactyly syndrome 31.2 HOXD13 HOXD12 HOXD11 HOXD10
3 polydactyly 30.1 LMBR1 HOXD13 HOXA13 GLI3
4 brachydactyly 29.7 HOXD9 HOXD13 HOXD12 HOXD11 HOXD10 CHST11
5 greig cephalopolysyndactyly syndrome 29.6 LMBR1 GLI3
6 chromosome 2q35 duplication syndrome 29.3 LMBR1 HOXD9 HOXD13 HOXD12 HOXD11 HOXA13
7 synpolydactyly 2 11.5
8 subcorneal pustular dermatosis 11.3
9 synpolydactyly 3 11.3
10 spondyloperipheral dysplasia 11.3
11 isolated delta-storage pool disease 11.1
12 pfeiffer syndrome 11.0
13 jawad syndrome 10.9
14 schizoid personality disorder 10.9
15 brachydactyly, type a3 10.3 HOXD13 EVX2
16 brachydactyly, type a4 10.3 HOXD13 HOXD12
17 acrorenal syndrome 10.2 HOXD13 GLI3
18 congenital limb malformation 10.2
19 brachydactyly, type e1 10.2 HOXD13 HOXD12
20 brachydactyly, type d 10.2 HOXD13 HOXD12 EVX2
21 hepatocellular carcinoma 10.1
22 status epilepticus 10.1
23 anus, imperforate 10.1 HOXD13 GLI3
24 townes-brocks syndrome 10.1 HOXD13 HOXD11 GLI3
25 diffuse large b-cell lymphoma 10.1
26 b-cell lymphoma 10.1
27 currarino syndrome 10.1 HOXD@ HOXD13
28 isolated growth hormone deficiency type iii 10.0 HOXD13 HOXA13
29 pancreatic cancer 10.0
30 follicular lymphoma 10.0
31 cystic echinococcosis 10.0
32 echinococcosis 10.0
33 hepatitis b 10.0
34 hepatitis 10.0
35 glioma 10.0
36 glial tumor 10.0
37 metacarpal 4-5 fusion 10.0 LMBR1 HOXD12
38 scoliosis 10.0
39 hypospadias 10.0
40 skin tag 10.0 LMBR1 GLI3
41 vertical talus, congenital 10.0 HOXD12 HOXD11 HOXD10
42 bone development disease 9.9 LMBR1 HOXD13 GLI3
43 systemic lupus erythematosus 9.9
44 ovarian cancer 9.9
45 rheumatoid arthritis 9.9
46 neural tube defects 9.9
47 storage pool platelet disease 9.9
48 lung cancer 9.9
49 acute pancreatitis 9.9
50 glioblastoma 9.9

Graphical network of the top 20 diseases related to Synpolydactyly:



Diseases related to Synpolydactyly

Symptoms & Phenotypes for Synpolydactyly

Human phenotypes related to Synpolydactyly:

58 (show all 12)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 sandal gap 58 Occasional (29-5%)
2 clinodactyly of the 5th finger 58 Frequent (79-30%)
3 abnormality of the metacarpal bones 58 Frequent (79-30%)
4 symphalangism affecting the phalanges of the hand 58 Frequent (79-30%)
5 camptodactyly of finger 58 Frequent (79-30%)
6 short foot 58 Frequent (79-30%)
7 postaxial foot polydactyly 58 Frequent (79-30%)
8 short palm 58 Frequent (79-30%)
9 preaxial foot polydactyly 58 Occasional (29-5%)
10 2-3 toe syndactyly 58 Very frequent (99-80%)
11 3-4 finger syndactyly 58 Very frequent (99-80%)
12 mesoaxial polydactyly 58 Occasional (29-5%)

MGI Mouse Phenotypes related to Synpolydactyly:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 10.2 CHST11 EVX2 FBLN1 GLI3 HOXA13 HOXD10
2 limbs/digits/tail MP:0005371 10.18 CHST11 EVX2 FBLN1 GLI3 HOXA13 HOXD10
3 endocrine/exocrine gland MP:0005379 10.01 CHST11 FBLN1 GLI3 HOXA13 HOXD13 HOXD9
4 muscle MP:0005369 9.8 CHST11 FBLN1 HOXD10 HOXD12 HOXD13 HOXD9
5 renal/urinary system MP:0005367 9.76 CHST11 FBLN1 GLI3 HOXA13 HOXD10 HOXD11
6 reproductive system MP:0005389 9.73 EVX2 GLI3 HOXA13 HOXD10 HOXD11 HOXD12
7 skeleton MP:0005390 9.47 CHST11 EVX2 FBLN1 GLI3 HOXA13 HOXD10

Drugs & Therapeutics for Synpolydactyly

Search Clinical Trials , NIH Clinical Center for Synpolydactyly

Cochrane evidence based reviews: syndactyly, type 2

Genetic Tests for Synpolydactyly

Anatomical Context for Synpolydactyly

Publications for Synpolydactyly

Articles related to Synpolydactyly:

(show top 50) (show all 115)
# Title Authors PMID Year
1
Fork stalling and template switching as a mechanism for polyalanine tract expansion affecting the DYC mutant of HOXD13, a new murine model of synpolydactyly. 54 61
19546318 2009
2
Polyalanine repeat expansion mutations in the HOXD13 gene in Pakistani families with synpolydactyly. 61 54
19686284 2009
3
A G220V substitution within the N-terminal transcription regulating domain of HOXD13 causes a variant synpolydactyly phenotype. 61 54
19060004 2009
4
Association of hypospadias with hypoplastic synpolydactyly and role of HOXD13 gene mutations. 61 54
17656229 2007
5
Mutations in HOXD13 underlie syndactyly type V and a novel brachydactyly-syndactyly syndrome. 61 54
17236141 2007
6
Mutation analysis of HOXD13 gene in a Chinese pedigree with synpolydactyly. 61 54
15952114 2005
7
The pathophysiology of HOX genes and their role in cancer. 61 54
15643670 2005
8
[Genetic analysis of a Chinese pedigree with congenital synpolydactyly]. 61 54
14669516 2003
9
An acceptor splice site mutation in HOXD13 results in variable hand, but consistent foot malformations. 54 61
12900906 2003
10
Missense mutations in the homeodomain of HOXD13 are associated with brachydactyly types D and E. 54 61
12649808 2003
11
An I47L substitution in the HOXD13 homeodomain causes a novel human limb malformation by producing a selective loss of function. 54 61
12620993 2003
12
The mouse Hoxd13(spdh) mutation, a polyalanine expansion similar to human type II synpolydactyly (SPD), disrupts the function but not the expression of other Hoxd genes. 61 54
11543619 2001
13
Physical map of a 1.5 mb region on 12p11.2 harbouring a synpolydactyly associated chromosomal breakpoint. 61 54
10951517 2000
14
A new spontaneous mouse mutation of Hoxd13 with a polyalanine expansion and phenotype similar to human synpolydactyly. 54 61
9580668 1998
15
Physical mapping of the t(12;22) translocation breakpoints in a family with a complex type of 3/3'/4 synpolydactyly. 61 54
9730609 1998
16
Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract. 61 54
9207113 1997
17
Synpolydactyly in mice with a targeted deficiency in the HoxD complex. 54 61
8900279 1996
18
Genomic structure of HOXD13 gene: a nine polyalanine duplication causes synpolydactyly in two unrelated families. 61 54
8817328 1996
19
Altered growth and branching patterns in synpolydactyly caused by mutations in HOXD13. 61 54
8614804 1996
20
A large Turkish kindred with syndactyly type II (synpolydactyly). 1. Field investigation, clinical and pedigree data. 61 54
7666393 1995
21
Biallelic truncating variants in MAPKAPK5 cause a new developmental disorder involving neurological, cardiac, and facial anomalies combined with synpolydactyly. 61
33442026 2021
22
Unblending of Transcriptional Condensates in Human Repeat Expansion Disease. 61
32386547 2020
23
Biallelic variants in EFEMP1 in a man with a pronounced connective tissue phenotype. 61
31792352 2020
24
A Review of the Phenotype of Synpolydactyly Type 1 in Homozygous Patients: Defining the Relatively Long and Medially Deviated Big Toe with/without Cupping of the Forefoot as a Pathognomonic Feature in the Phenotype. 61
32509852 2020
25
A heterozygous duplication variant of the HOXD13 gene caused synpolydactyly type 1 with variable expressivity in a Chinese family. 61
31870337 2019
26
A novel missense in GLI3 possibly affecting one of the zinc finger domains may lead to postaxial synpolydactyly: case report. 61
31706290 2019
27
A Nonsense Mutation in HOXD13 Gene from A Chinese Family with Non-Syndromic Synpolydactyly. 61
31611522 2019
28
A rare TTC30B variant is identified as a candidate for synpolydactyly in a Chinese pedigree. 61
31306809 2019
29
Homozygous CHST11 mutation in chondrodysplasia, brachydactyly, overriding digits, clino-symphalangism and synpolydactyly. 61
29514872 2018
30
Classification of synpolydactyly: experience in 10 children. 61
29022776 2018
31
Composition and dosage of a multipartite enhancer cluster control developmental expression of Ihh (Indian hedgehog). 61
28846100 2017
32
Occurrence of Synpolydactyly and Omphalocele in a Fetus with a HOXD13 Mutation. 61
28794915 2017
33
[A novel mutation of GLI3 gene underlying synpolydactyly in a family]. 61
28777844 2017
34
Homozygous microdeletion of the ERI1 and MFHAS1 genes in a patient with intellectual disability, limb abnormalities, and cardiac malformation. 61
28488351 2017
35
Mutations in ARMC9, which Encodes a Basal Body Protein, Cause Joubert Syndrome in Humans and Ciliopathy Phenotypes in Zebrafish. 61
28625504 2017
36
Exome sequencing identifies a novel nonsense mutation of HOXD13 in a Chinese family with synpolydactyly. 61
27254532 2017
37
The Role of Hox in Pisiform and Calcaneus Growth Plate Formation and the Nature of the Zeugopod/Autopod Boundary. 61
27507801 2016
38
Familial pseudotail, scoliosis and synpolydactyly syndrome. 61
26525682 2016
39
A homozygous HOXD13 missense mutation causes a severe form of synpolydactyly with metacarpal to carpal transformation. 61
26581570 2016
40
Synpolydactyly of the hand: a radiographic classification. 61
26269507 2016
41
Homozygosity mapping identified a novel protein truncating mutation (p.Ser100Leufs*24) of the BBS9 gene in a consanguineous Pakistani family with Bardet Biedl syndrome. 61
26846096 2016
42
[Mutation analysis of HOXD13 gene in a Chinese family affected with autosomal dominant synpolydactyly]. 61
26252089 2015
43
Functional classification and mutation analysis of a synpolydactyly kindred. 61
25289061 2014
44
Long bone development requires a threshold of Hox function. 61
24930703 2014
45
Regulation of cell polarity in the cartilage growth plate and perichondrium of metacarpal elements by HOXD13 and WNT5A. 61
24161848 2014
46
Venturing into the overlap between pediatric orthopaedics and hand surgery. 61
24720302 2014
47
Mutations in the homeodomain of HOXD13 cause syndactyly type 1-c in two Chinese families. 61
24789103 2014
48
Joining the fingers: a HOXD13 Story. 61
24038517 2014
49
A splice donor site mutation in HOXD13 underlies synpolydactyly with cortical bone thinning. 61
24055421 2013
50
A novel mutation outside homeodomain of HOXD13 causes synpolydactyly in a Chinese family. 61
23948678 2013

Variations for Synpolydactyly

ClinVar genetic disease variations for Synpolydactyly:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FBLN1 NM_006486.3(FBLN1):c.32C>A (p.Pro11Gln) SNV Uncertain significance 1031049 GRCh37: 22:45898897-45898897
GRCh38: 22:45503017-45503017

Expression for Synpolydactyly

Search GEO for disease gene expression data for Synpolydactyly.

Pathways for Synpolydactyly

GO Terms for Synpolydactyly

Cellular components related to Synpolydactyly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin GO:0000785 9.23 HOXD9 HOXD4 HOXD13 HOXD12 HOXD11 HOXD10

Biological processes related to Synpolydactyly according to GeneCards Suite gene sharing:

(show all 23)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription by RNA polymerase II GO:0045944 10.07 SFRP2 HOXD9 HOXD4 HOXD13 HOXD10 HOXA13
2 regulation of transcription by RNA polymerase II GO:0006357 10.07 RBBP8 HOXD9 HOXD4 HOXD13 HOXD12 HOXD11
3 regulation of transcription, DNA-templated GO:0006355 10.06 HOXD9 HOXD4 HOXD13 HOXD12 HOXD11 HOXD10
4 multicellular organism development GO:0007275 9.96 SFRP2 LNPK HOXD9 HOXD4 HOXD13 HOXD12
5 regulation of cell proliferation GO:0042127 9.84 SFRP2 HOXD13 GLI3 CHST11
6 skeletal system development GO:0001501 9.8 HOXD13 HOXD12 HOXD10 HOXA13
7 pattern specification process GO:0007389 9.69 HOXD13 HOXD12 GLI3
8 embryonic forelimb morphogenesis GO:0035115 9.65 LNPK HOXD9 HOXA13
9 proximal/distal pattern formation GO:0009954 9.63 HOXD9 HOXD10 GLI3
10 embryonic limb morphogenesis GO:0030326 9.62 HOXD13 HOXD10 GLI3 CHST11
11 mammary gland development GO:0030879 9.61 HOXD9 GLI3
12 developmental growth GO:0048589 9.61 GLI3 CHST11
13 limb morphogenesis GO:0035108 9.61 HOXD13 GLI3 EVX2
14 chondrocyte development GO:0002063 9.6 SFRP2 CHST11
15 male genitalia development GO:0030539 9.59 HOXD13 HOXA13
16 post-anal tail morphogenesis GO:0036342 9.58 SFRP2 CHST11
17 prostate gland development GO:0030850 9.58 HOXD13 GLI3
18 peripheral nervous system neuron development GO:0048935 9.57 HOXD9 HOXD10
19 hindlimb morphogenesis GO:0035137 9.56 HOXD9 HOXD10
20 forelimb morphogenesis GO:0035136 9.55 HOXD9 HOXD10
21 embryonic skeletal system morphogenesis GO:0048704 9.55 HOXD9 HOXD4 HOXD10 GLI3 CHST11
22 anterior/posterior pattern specification GO:0009952 9.43 SFRP2 HOXD9 HOXD4 HOXD13 HOXD10 GLI3
23 embryonic digit morphogenesis GO:0042733 9.17 SFRP2 LNPK LMBR1 HOXD13 HOXD12 GLI3

Molecular functions related to Synpolydactyly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 9.96 RBBP8 HOXD9 HOXD4 HOXD13 HOXD12 HOXD11
2 DNA-binding transcription factor activity GO:0003700 9.8 HOXD9 HOXD4 HOXD13 HOXD10 HOXA13 GLI3
3 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.76 HOXD9 HOXD4 HOXD13 HOXD11 HOXD10 HOXA13
4 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.73 HOXD4 HOXD13 HOXD10 HOXA13
5 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 9.67 HOXD9 HOXD4 HOXD10 GLI3
6 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.61 HOXD9 HOXD4 HOXD13 HOXD12 HOXD11 HOXD10
7 fibronectin binding GO:0001968 9.4 SFRP2 FBLN1
8 sequence-specific double-stranded DNA binding GO:1990837 9.28 HOXD9 HOXD4 HOXD13 HOXD12 HOXD11 HOXD10

Sources for Synpolydactyly

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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