SPD1
MCID: SYN084
MIFTS: 36

Synpolydactyly 1 (SPD1)

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

Aliases & Classifications for Synpolydactyly 1

MalaCards integrated aliases for Synpolydactyly 1:

Name: Synpolydactyly 1 57 72 29 6 70
Spd1 57 58 72
Synpolydactyly, Vordingborg Type 58
Syndactyly, Type Ii; Sdty2 57
Synpolydactyly, Type 1 39
Synpolydactyly Type 1 58
Sd2, Vordingborg Type 58
Spd, Vordingborg Type 58
Syndactyly, Type Ii 57
Syndactyly Type 2 72
Sdty2 57
Sdyt2 72
Sd2a 58

Characteristics:

Orphanet epidemiological data:

58
synpolydactyly type 1
Inheritance: Autosomal dominant;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
marked intrafamilial variability, with homozygotes exhibiting a more severe phenotype and heterozygotes showing milder features


HPO:

31
synpolydactyly 1:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

OMIM® 57 186000
ICD10 via Orphanet 33 Q70.0 Q70.2
UMLS via Orphanet 71 C1861367
Orphanet 58 ORPHA295195
UMLS 70 C1861367

Summaries for Synpolydactyly 1

OMIM® : 57 Synpolydactyly (SPD), or syndactyly type II, is defined as a connection between the middle and ring fingers and fourth and fifth toes, variably associated with postaxial polydactyly in the same digits. Minor local anomalies and various metacarpal or metatarsal abnormalities may be present (summary by Merlob and Grunebaum, 1986). In some families with SPD, the foot anomalies are characterized by preaxial as well as postaxial polydactyly, and appear to be fully penetrant. The more severe features of classic SPD, involving 3/4 synpolydactyly in the hands and 4/5 synpolydactyly in the feet, also occur, but at reduced penetrance. This foot phenotype is not seen in patients with classic SPD due to HOXD13 polyalanine tract expansions (Goodman et al., 1998). Malik (2012) reviewed the syndactylies, noting that the extreme phenotypic heterogeneity observed in SPD families consists of approximately 18 clinical variants that can be 'lumped' into 3 categories: typical SPD features, minor variants, and unusual phenotypes. (186000) (Updated 05-Apr-2021)

MalaCards based summary : Synpolydactyly 1, also known as spd1, is related to synpolydactyly and brachydactyly. An important gene associated with Synpolydactyly 1 is HOXD13 (Homeobox D13). Affiliated tissues include bone, breast and t cells, and related phenotypes are 2-3 toe syndactyly and 3-4 finger syndactyly

UniProtKB/Swiss-Prot : 72 Synpolydactyly 1: Limb malformation that shows a characteristic manifestation in both hands and feet. This condition is inherited as an autosomal dominant trait with reduced penetrance.

Related Diseases for Synpolydactyly 1

Diseases in the Synpolydactyly family:

Synpolydactyly 1 Synpolydactyly 2
Synpolydactyly 3

Diseases related to Synpolydactyly 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 synpolydactyly 29.3 HOXD13 CHST11
2 brachydactyly 29.2 HOXD13 CHST11
3 pfeiffer syndrome 11.0
4 synpolydactyly 2 10.1
5 chromosome 2q35 duplication syndrome 10.0
6 polydactyly 10.0
7 greig cephalopolysyndactyly syndrome 9.9

Graphical network of the top 20 diseases related to Synpolydactyly 1:



Diseases related to Synpolydactyly 1

Symptoms & Phenotypes for Synpolydactyly 1

Human phenotypes related to Synpolydactyly 1:

31 (show all 21)
# Description HPO Frequency HPO Source Accession
1 2-3 toe syndactyly 31 hallmark (90%) HP:0004691
2 3-4 finger syndactyly 31 hallmark (90%) HP:0006097
3 clinodactyly of the 5th finger 31 frequent (33%) HP:0004209
4 abnormality of the metacarpal bones 31 frequent (33%) HP:0001163
5 symphalangism affecting the phalanges of the hand 31 frequent (33%) HP:0009773
6 camptodactyly of finger 31 frequent (33%) HP:0100490
7 short foot 31 frequent (33%) HP:0001773
8 postaxial foot polydactyly 31 frequent (33%) HP:0001830
9 short palm 31 frequent (33%) HP:0004279
10 sandal gap 31 occasional (7.5%) HP:0001852
11 preaxial foot polydactyly 31 occasional (7.5%) HP:0001841
12 mesoaxial polydactyly 31 occasional (7.5%) HP:0100260
13 finger syndactyly 31 HP:0006101
14 short middle phalanx of the 5th finger 31 HP:0004220
15 mesoaxial hand polydactyly 31 HP:0006159
16 6 metacarpals 31 HP:0001501
17 2nd-5th toe middle phalangeal hypoplasia 31 HP:0008083
18 broad hallux 31 HP:0010055
19 contracture of the proximal interphalangeal joint of the 5th finger 31 HP:0009185
20 y-shaped metacarpals 31 HP:0006042
21 4-5 toe syndactyly 31 HP:0004692

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal Hands:
6 metacarpals
mesoaxial polydactyly
y-shaped metacarpals
brachydactyly (in some patients)
syndactyly, 3rd-4th finger
more
Skin Nails Hair Nails:
absent or underdeveloped nails (in some patients)
absent or rudimentary nails in syndactylous web (in some patients)

Skeletal Feet:
2nd-5th toe middle phalangeal hypoplasia
broad hallux
postaxial polydactyly
4th-5th toe syndactyly
preaxial polydactyly (rare)
more

Clinical features from OMIM®:

186000 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Synpolydactyly 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 limbs/digits/tail MP:0005371 8.62 CHST11 HOXD13

Drugs & Therapeutics for Synpolydactyly 1

Search Clinical Trials , NIH Clinical Center for Synpolydactyly 1

Genetic Tests for Synpolydactyly 1

Genetic tests related to Synpolydactyly 1:

# Genetic test Affiliating Genes
1 Synpolydactyly 1 29 HOXD13

Anatomical Context for Synpolydactyly 1

MalaCards organs/tissues related to Synpolydactyly 1:

40
Bone, Breast, T Cells

Publications for Synpolydactyly 1

Articles related to Synpolydactyly 1:

(show top 50) (show all 96)
# Title Authors PMID Year
1
A splice donor site mutation in HOXD13 underlies synpolydactyly with cortical bone thinning. 61 57 6
24055421 2013
2
A nonsense mutation in the HOXD13 gene underlies synpolydactyly with incomplete penetrance. 61 57 6
21814222 2011
3
A large Turkish kindred with syndactyly type II (synpolydactyly). 1. Field investigation, clinical and pedigree data. 61 6 57
7666393 1995
4
Mutations in the homeodomain of HOXD13 cause syndactyly type 1-c in two Chinese families. 57 6
24789103 2014
5
A novel mutation outside homeodomain of HOXD13 causes synpolydactyly in a Chinese family. 57 6
23948678 2013
6
A novel non-synonymous mutation in the homeodomain of HOXD13 causes synpolydactyly in a Chinese family. 57 6
22374128 2012
7
An N-terminal G11A mutation in HOXD13 causes synpolydactyly and interferes with Gli3R function during limb pre-patterning. 6 57
22373878 2012
8
A G220V substitution within the N-terminal transcription regulating domain of HOXD13 causes a variant synpolydactyly phenotype. 6 57
19060004 2009
9
A 72-year-old Danish puzzle resolved--comparative analysis of phenotypes in families with different-sized HOXD13 polyalanine expansions. 6 57
16222680 2005
10
An acceptor splice site mutation in HOXD13 results in variable hand, but consistent foot malformations. 6 57
12900906 2003
11
Severe digital abnormalities in a patient heterozygous for both a novel missense mutation in HOXD13 and a polyalanine tract expansion in HOXA13. 6 57
12414828 2002
12
Deletions in HOXD13 segregate with an identical, novel foot malformation in two unrelated families. 57 6
9758628 1998
13
Genomic structure of HOXD13 gene: a nine polyalanine duplication causes synpolydactyly in two unrelated families. 6 57
8817328 1996
14
Joining the fingers: a HOXD13 Story. 57
24038517 2014
15
Syndactyly: phenotypes, genetics and current classification. 57
22333904 2012
16
Eight-alanine duplication in homeobox D13 in a Chinese family with synpolydactyly. 57
22406499 2012
17
Type II familial synpolydactyly: report on two families with an emphasis on variations of expression. 57
20717165 2011
18
Synpolydactyly: clinical and molecular advances. 57
18177473 2008
19
Novel mutations of the HOXD13 gene in hand and foot malformations. 6
18399101 2007
20
Mutations in HOXD13 underlie syndactyly type V and a novel brachydactyly-syndactyly syndrome. 57
17236141 2007
21
The other trinucleotide repeat: polyalanine expansion disorders. 6
15917204 2005
22
A molecular pathogenesis for transcription factor associated poly-alanine tract expansions. 6
15333588 2004
23
Alanine tracts: the expanding story of human illness and trinucleotide repeats. 6
14698619 2004
24
HOXD13 polyalanine tract expansion in classical synpolydactyly type Vordingborg. 57
12116248 2002
25
A 117-kb microdeletion removing HOXD9-HOXD13 and EVX2 causes synpolydactyly. 57
11778160 2002
26
Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract. 6
9207113 1997
27
Synpolydactyly in mice with a targeted deficiency in the HoxD complex. 57
8900279 1996
28
Altered growth and branching patterns in synpolydactyly caused by mutations in HOXD13. 57
8614804 1996
29
A mutational analysis of the 5' HoxD genes: dissection of genetic interactions during limb development in the mouse. 6
8620844 1996
30
Localization of the syndactyly type II (synpolydactyly) locus to 2q31 region and identification of tight linkage to HOXD8 intragenic marker. 57
7581388 1995
31
A large Turkish kindred with syndactyly type II (synpolydactyly). 2. Homozygous phenotype? 57
7666394 1995
32
Synpolydactyly (type II syndactyly) with aplasia/hypoplasia of the middle phalanges of the toes: report on a family with eight affected members in four generations. 57
7717427 1995
33
Type II syndactyly or synpolydactyly. 57
3014149 1986
34
Treatment of central polydactyly. 57
4322173 1971
35
Type II syndactyly. 57
4298538 1968
36
Zygodactyly and associated variations in a Utah family. 57
20292747 1947
37
Variation of expression of polydactyly. 57
20985729 1946
38
Serum levels of soluble PD1 in pemphigus vulgaris: A useful marker for disease severity. 61
32920962 2021
39
Correlation of sPD1 with Procalcitonin and C-Reactive Protein Levels in Patients with Sepsis. 61
33650816 2021
40
Eliminating mesothelioma by AAV-vectored, PD1-based vaccination in the tumor microenvironment. 61
33614918 2021
41
Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes. 61
33024089 2020
42
Exploratory Pilot Study of Circulating Biomarkers in Metastatic Renal Cell Carcinoma. 61
32937860 2020
43
Increase of emm1 isolates among group A Streptococcus strains causing scarlet fever in Shanghai, China. 61
32562850 2020
44
Soluble PD1 levels are increased with disease activity in paediatric onset autoimmune hepatitis and inflammatory bowel disease. 61
32370568 2020
45
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
46
A heterozygous duplication variant of the HOXD13 gene caused synpolydactyly type 1 with variable expressivity in a Chinese family. 61
31870337 2019
47
Dietary soybean antigen impairs growth and health through stress-induced non-specific immune responses in Pacific white shrimp, Litopenaeus vannamei. 61
30261296 2019
48
Neonatal Antibiotic Treatment Is Associated With an Altered Circulating Immune Marker Profile at 1 Year of Age. 61
31998285 2019
49
Increased antitumor activities of glypican-3-specific chimeric antigen receptor-modified T cells by coexpression of a soluble PD1-CH3 fusion protein. 61
30078052 2018
50
Soluble PD-1-based vaccine targeting MUC1 VNTR and survivin improves anti-tumor effect. 61
29894719 2018

Variations for Synpolydactyly 1

ClinVar genetic disease variations for Synpolydactyly 1:

6 (show all 17)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HOXD13 NM_000523.4(HOXD13):c.323_336del (p.Pro108fs) Deletion Pathogenic 14867 rs878854343 GRCh37: 2:176957941-176957954
GRCh38: 2:176093213-176093226
2 HOXD13 NM_000523.4(HOXD13):c.834del (p.Lys279fs) Deletion Pathogenic 14868 rs878854344 GRCh37: 2:176959260-176959260
GRCh38: 2:176094532-176094532
3 HOXD13 NM_000523.4(HOXD13):c.782-2del Deletion Pathogenic 14871 rs764838478 GRCh37: 2:176959206-176959206
GRCh38: 2:176094478-176094478
4 HOXD13 NM_000523.4(HOXD13):c.916C>T (p.Arg306Trp) SNV Pathogenic 14872 rs28933082 GRCh37: 2:176959342-176959342
GRCh38: 2:176094614-176094614
5 HOXD13 NM_000523.4(HOXD13):c.683G>T (p.Gly228Val) SNV Pathogenic 14876 rs121912541 GRCh37: 2:176958301-176958301
GRCh38: 2:176093573-176093573
6 HOXD13 NM_000523.4(HOXD13):c.683G>C (p.Gly228Ala) SNV Pathogenic 225654 rs121912541 GRCh37: 2:176958301-176958301
GRCh38: 2:176093573-176093573
7 HOXD13 NM_000523.4(HOXD13):c.917G>A (p.Arg306Gln) SNV Pathogenic 225652 rs879255265 GRCh37: 2:176959343-176959343
GRCh38: 2:176094615-176094615
8 HOXD13 NM_000523.4(HOXD13):c.742C>T (p.Gln248Ter) SNV Pathogenic 225650 rs878854400 GRCh37: 2:176958360-176958360
GRCh38: 2:176093632-176093632
9 HOXD13 NM_000523.4(HOXD13):c.916C>G (p.Arg306Gly) SNV Pathogenic 225656 rs28933082 GRCh37: 2:176959342-176959342
GRCh38: 2:176094614-176094614
10 HOXD13 NM_000523.4(HOXD13):c.781+1G>A SNV Pathogenic 225653 rs886037831 GRCh37: 2:176958400-176958400
GRCh38: 2:176093672-176093672
11 HOXD13 NM_000523.4(HOXD13):c.744_747del (p.Gln248fs) Deletion Pathogenic 689765 rs1574943406 GRCh37: 2:176958359-176958362
GRCh38: 2:176093631-176093634
12 HOXD13 NM_000523.4(HOXD13):c.32G>C (p.Gly11Ala) SNV Pathogenic 225651 rs536639583 GRCh37: 2:176957650-176957650
GRCh38: 2:176092922-176092922
13 HOXD13 NM_000523.4(HOXD13):c.820C>T (p.Arg274Ter) SNV Pathogenic 374019 rs200750564 GRCh37: 2:176959246-176959246
GRCh38: 2:176094518-176094518
14 HOXD13 NM_000523.4(HOXD13):c.212_213insGGCGGCTGCGGCGGCGGCAGCGGCAGC (p.Ala63_Ala71dup) Insertion Pathogenic 916250 GRCh37: 2:176957822-176957823
GRCh38: 2:176093094-176093095
15 HOXD13 NM_000523.4(HOXD13):c.209_210insGGCTGCGGCGGCGGCAGCGGC (p.Ala65_Ala71dup) Insertion Pathogenic 14873 rs878854345 GRCh37: 2:176957822-176957823
GRCh38: 2:176093094-176093095
16 CHST11 NM_018413.6(CHST11):c.482_496del (p.Leu161_Asn165del) Deletion Uncertain significance 559505 rs1566067709 GRCh37: 12:105151000-105151014
GRCh38: 12:104757222-104757236
17 HOXD13 NM_000523.4(HOXD13):c.709G>C (p.Gly237Arg) SNV Uncertain significance 930707 GRCh37: 2:176958327-176958327
GRCh38: 2:176093599-176093599

UniProtKB/Swiss-Prot genetic disease variations for Synpolydactyly 1:

72
# Symbol AA change Variation ID SNP ID
1 HOXD13 p.Arg306Trp VAR_031651 rs28933082
2 HOXD13 p.Thr313Arg VAR_075400 rs143206399
3 HOXD13 p.Arg306Gly VAR_076833 rs28933082
4 HOXD13 p.Arg306Gln VAR_076834 rs879255265

Expression for Synpolydactyly 1

Search GEO for disease gene expression data for Synpolydactyly 1.

Pathways for Synpolydactyly 1

GO Terms for Synpolydactyly 1

Biological processes related to Synpolydactyly 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of cell proliferation GO:0042127 9.16 HOXD13 CHST11
2 embryonic digit morphogenesis GO:0042733 8.96 HOXD13 CHST11
3 embryonic limb morphogenesis GO:0030326 8.62 HOXD13 CHST11

Sources for Synpolydactyly 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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