GUTTS
MCID: PRX093
MIFTS: 33

Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias (GUTTS)

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

Aliases & Classifications for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

MalaCards integrated aliases for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias:

Name: Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias 57
Guttmacher Syndrome 57 12 20 58 72 36 29 13 6 15 39
Preaxial Deficiency, Postaxial Polydactyly and Hypospadias 20 44 70
Autosomal Dominant Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias 12 20
Preaxial Deficiency-Postaxial Polydactyly-Hypospadias Syndrome 12 58
Gutts 72

Characteristics:

Orphanet epidemiological data:

58
guttmacher syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

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

Miscellaneous:
based on description of 3 individuals in 1 family


HPO:

31
preaxial deficiency, postaxial polydactyly, and hypospadias:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0111544
OMIM® 57 176305
KEGG 36 H00859
MeSH 44 C538278
SNOMED-CT 67 722452004
MESH via Orphanet 45 C538278
ICD10 via Orphanet 33 Q87.2
UMLS via Orphanet 71 C1867801
Orphanet 58 ORPHA2957
MedGen 41 C1867801
UMLS 70 C1867801

Summaries for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 2957 Definition Guttmacher syndrome is an extremely rare syndrome characterized by hypoplastic thumbs and halluces, 5th finger clinobrachydactyly, postaxial polydactyly of the hands, short or uniphalangeal 2nd toes with absent nails and hypospadias. Epidemiology It has been described in a father and his son and daughter. Clinical description The affected patients have normal mental development. Except for postaxial polydactyly of the hands and uniphalangeal 2nd toes with absent nails, features are in common with hand-foot-genital syndrome (HFGS, see this term) caused by mutations in the HOXA13 gene. Etiology In all three affected individuals with Guttmacher syndrome, two different sequence alterations were identified in HOXA13 gene: a de novo missense mutation and a deletion in the promoter region of the gene, inherited from an unaffected parent, which may contribute to the phenotype in the affected individuals. Genetic counseling The condition is inherited in an autosomal dominant manner.

MalaCards based summary : Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias, also known as guttmacher syndrome, is related to hypospadias and hand-foot-genital syndrome. An important gene associated with Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias is HOXA13 (Homeobox A13). Related phenotypes are brachydactyly and short thumb

Disease Ontology : 12 A syndrome characterized by preaxial deficiencies of the hands and feet, postaxial polydactyly of the hands, and hypospadias that has material basis in heterozygous mutation in HOXA13 on chromosome 7p15.2.

KEGG : 36 Guttmacher syndrome is a disorder of distal limb and genital tract that resembles hand-foot-genital syndrome (HFGS). In addition to the typical features of HFGS, namely the combination of hypoplastic thumbs and halluces, 5th finger clinobrachydactyly and hypospadias, Guttmacher syndrome displays postaxial polydactyly of the hands and short or uniphalangeal 2nd toes with absent nails.

UniProtKB/Swiss-Prot : 72 Guttmacher syndrome: Dominantly inherited combination of distal limb and genital tract abnormalities. It has several features in common with hand-foot- genital syndrome, including hypoplastic first digits and hypospadias. Typical features not seen in hand-foot-genital syndrome include postaxial polydactyly of the hands and uniphalangeal second toes with absent nails.

More information from OMIM: 176305

Related Diseases for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

Graphical network of the top 20 diseases related to Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias:



Diseases related to Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

Symptoms & Phenotypes for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

Human phenotypes related to Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias:

31
# Description HPO Frequency HPO Source Accession
1 brachydactyly 31 HP:0001156
2 short thumb 31 HP:0009778
3 postaxial hand polydactyly 31 HP:0001162
4 glandular hypospadias 31 HP:0000807
5 short 2nd toe 31 HP:0001885

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal Hands:
short thumbs
postaxial polydactyly of hands
limited range of motion of interphalangeal joints
brachydactyly, mild (5th finger)

Skeletal Feet:
rudimentary halluces
uniphalangeal second toes

Genitourinary External Genitalia Male:
glanular hypospadias

Skin Nails Hair Nails:
missing nail on halluces and second toes

Clinical features from OMIM®:

176305 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias according to GeneCards Suite gene sharing:

26 (show all 12)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 9.47 EMX2
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-105 9.47 EMX2
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.47 HOXC13
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.47 HOXA13
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-177 9.47 HOXA13 HOXC13
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-19 9.47 HOXA13
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-190 9.47 HOXC13
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-211 9.47 EMX2
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-214 9.47 HOXC13
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.47 HOXC13
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-22 9.47 EMX2 HOXC13
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-85 9.47 HOXC13

MGI Mouse Phenotypes related to Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.92 CBX2 EMX2 HOXA13 HOXA2 HOXB1 HOXC13
2 mortality/aging MP:0010768 9.91 CBX2 EMX2 HOXA13 HOXA2 HOXB1 HOXC13
3 craniofacial MP:0005382 9.88 CBX2 EMX2 HOXA2 HOXB1 HOXC13 HOXD4
4 digestive/alimentary MP:0005381 9.77 CBX2 HOXA13 HOXA2 HOXC13 HOXD13
5 reproductive system MP:0005389 9.63 CBX2 EMX2 HOXA13 HOXD10 HOXD13 HOXD4
6 skeleton MP:0005390 9.61 CBX2 EMX2 HOXA13 HOXA2 HOXB1 HOXC13
7 vision/eye MP:0005391 9.1 CBX2 EMX2 HOXA13 HOXB1 HOXC13 HOXD13

Drugs & Therapeutics for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

Search Clinical Trials , NIH Clinical Center for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

Cochrane evidence based reviews: preaxial deficiency, postaxial polydactyly and hypospadias

Genetic Tests for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

Genetic tests related to Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias:

# Genetic test Affiliating Genes
1 Guttmacher Syndrome 29 HOXA13

Anatomical Context for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

Publications for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

Articles related to Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias:

# Title Authors PMID Year
1
A HOXA13 allele with a missense mutation in the homeobox and a dinucleotide deletion in the promoter underlies Guttmacher syndrome. 61 6 57
11968094 2002
2
Autosomal dominant preaxial deficiency, postaxial polydactyly, and hypospadias. 61 57 6
8484413 1993
3
Severe manifestations of hand-foot-genital syndrome associated with a novel HOXA13 mutation. 61
24934387 2014

Variations for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

ClinVar genetic disease variations for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HOXA13 HOXA13, GLN50LEU AND 2-BP DEL, -79GC, PROMOTER Deletion Pathogenic 14893 GRCh37:
GRCh38:

UniProtKB/Swiss-Prot genetic disease variations for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias:

72
# Symbol AA change Variation ID SNP ID
1 HOXA13 p.Gln371Leu VAR_017775

Expression for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

Search GEO for disease gene expression data for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias.

Pathways for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

GO Terms for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

Cellular components related to Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleoplasm GO:0005654 9.63 HOXD4 HOXD13 HOXD10 HOXA2 HOXA13 CBX2
2 nucleus GO:0005634 9.61 HOXD4 HOXD13 HOXD10 HOXC13 HOXB1 HOXA2
3 chromatin GO:0000785 9.23 HOXD4 HOXD13 HOXD10 HOXC13 HOXB1 HOXA2

Biological processes related to Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription by RNA polymerase II GO:0006357 9.92 HOXD4 HOXD13 HOXD10 HOXC13 HOXB1 HOXA2
2 positive regulation of transcription by RNA polymerase II GO:0045944 9.91 HOXD4 HOXD13 HOXD10 HOXC13 HOXB1 HOXA2
3 regulation of transcription, DNA-templated GO:0006355 9.76 HOXD4 HOXD13 HOXD10 HOXC13 HOXB1 HOXA2
4 skeletal system development GO:0001501 9.63 HOXD13 HOXD10 HOXA13
5 anatomical structure morphogenesis GO:0009653 9.61 HOXC13 HOXB1 HOXA13
6 pattern specification process GO:0007389 9.58 HOXD13 HOXB1 HOXA2
7 embryonic skeletal system morphogenesis GO:0048704 9.56 HOXD4 HOXD10 HOXB1 HOXA2
8 multicellular organism development GO:0007275 9.56 HOXD4 HOXD13 HOXD10 HOXC13 HOXB1 HOXA2
9 embryonic limb morphogenesis GO:0030326 9.49 HOXD13 HOXD10
10 male genitalia development GO:0030539 9.48 HOXD13 HOXA13
11 anterior/posterior pattern specification GO:0009952 9.17 HOXD4 HOXD13 HOXD10 HOXC13 HOXB1 HOXA2

Molecular functions related to Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.86 HOXD4 HOXD13 HOXD10 HOXC13 HOXB1 HOXA2
2 DNA binding GO:0003677 9.81 HOXD4 HOXD13 HOXD10 HOXC13 HOXB1 HOXA2
3 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.8 HOXD4 HOXD13 HOXD10 HOXC13 HOXB1 HOXA13
4 DNA-binding transcription factor activity GO:0003700 9.77 HOXD4 HOXD13 HOXD10 HOXA2 HOXA13
5 chromatin binding GO:0003682 9.71 HOXD13 HOXD10 HOXC13 CBX2
6 sequence-specific DNA binding GO:0043565 9.65 HOXB1 HOXA2 HOXA13
7 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 9.61 HOXD4 HOXD10 HOXB1
8 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.56 HOXD4 HOXD13 HOXD10 HOXC13 HOXB1 HOXA2
9 proximal promoter sequence-specific DNA binding GO:0000987 9.46 HOXD13 HOXA13
10 sequence-specific double-stranded DNA binding GO:1990837 9.23 HOXD4 HOXD13 HOXD10 HOXC13 HOXB1 HOXA2

Sources for Preaxial Deficiency, Postaxial Polydactyly, and Hypospadias

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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