SHFM
MCID: SPL061
MIFTS: 39

Split Hand-Foot Malformation (SHFM)

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

Aliases & Classifications for Split Hand-Foot Malformation

MalaCards integrated aliases for Split Hand-Foot Malformation:

Name: Split Hand-Foot Malformation 12 15
Split-Hand/foot Malformation 37 6 73
Ectrodactyly 53 44 73
Split Hand Foot Malformation 53
Split Hand Foot Deformity 1 73
Split Hand Foot Deformity 73
Lobster-Claw Deformity 12
Split-Hand Deformity 12
Shfm 53

Classifications:



External Ids:

Disease Ontology 12 DOID:0090020
ICD10 33 Q71.6 Q71.60
ICD9CM 35 755.58
MeSH 44 C574275
SNOMED-CT 68 13624003 81208006
KEGG 37 H00471

Summaries for Split Hand-Foot Malformation

NIH Rare Diseases : 53 Split hand foot malformation (SHFM) is a type of birth defect that consists of missing digits (fingers and/or toes), a deep cleft down the center of the hand or foot, and fusion of remaining digits. The severity of this condition varies widely among affected individuals. SHFM is sometimes called ectrodactyly; however, this is a nonspecific term used to describe missing digits. SHFM may occur by itself (isolated) or it may be part of a syndrome with abnormalities in other parts of the body. At least six different forms of isolated SHFM have been described. Each type is associated with a different underlying genetic cause. SHFM1 has been linked to chromosome 7, and SHFM2 is linked to the X chromosome. SHFM3 is caused by a duplication of chromosome 10 at position 10q24. Changes (mutations) in the TP63 gene cause SHFM4. SHFM5 is linked to chromosome 2, and SHFM6 is caused by mutations in the WNT10B gene. SHFM may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner.

MalaCards based summary : Split Hand-Foot Malformation, also known as split-hand/foot malformation, is related to split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive and split-hand/foot malformation 3. An important gene associated with Split Hand-Foot Malformation is FBXW4 (F-Box And WD Repeat Domain Containing 4), and among its related pathways/superpathways is Signaling pathways regulating pluripotency of stem cells. Affiliated tissues include bone and heart, and related phenotypes are embryo and limbs/digits/tail

Disease Ontology : 12 A bone development disease characterized by malformation of the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients also have mental retardation, ectodermal and craniofacial findings, and orofacial clefting.

Related Diseases for Split Hand-Foot Malformation

Diseases in the Split Hand-Foot Malformation family:

Split-Hand/foot Malformation 1 Split-Hand/foot Malformation 6
Split-Hand/foot Malformation 3 Split-Hand/foot Malformation 2
Split-Hand/foot Malformation 4 Split-Hand/foot Malformation 5

Diseases related to Split Hand-Foot Malformation via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 152)
# Related Disease Score Top Affiliating Genes
1 split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive 34.6 DLX5 SEM1
2 split-hand/foot malformation 3 34.4 FBXW4 SEM1 WNT10B
3 split-hand/foot malformation 1 34.1 DLX5 MAP3K20 SEM1 TP63
4 split-hand/foot malformation 5 33.9 DLX5 FBXW4 SEM1 TP63 WNT10B
5 split-hand/foot malformation 4 33.8 DLX5 FBXW4 SEM1 TP63 WNT10B
6 split-hand/foot malformation 2 33.7 DLX5 FBXW4 SEM1 TP63 WNT10B
7 split-hand/foot malformation 6 33.6 BHLHA9 DLX5 FBXW4 SEM1 TP63 WNT10B
8 isolated split hand-split foot malformation 32.1 DLX5 SEM1 TP63 WNT10B
9 cleft lip/palate 29.8 FGFR1 TP63
10 rapp-hodgkin syndrome 29.6 DLX5 SEM1 TP63
11 split-hand/foot malformation with long bone deficiency 1 12.8
12 split hand/foot malformation x-linked 12.8
13 ulnar hypoplasia with lobster-claw deformity of feet 12.7
14 split-hand/foot malformation with long bone deficiency 2 12.6
15 ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome 12.5
16 chromosome 17p13.3, telomeric, duplication syndrome 12.3
17 fibular aplasia ectrodactyly 12.3
18 intellectual disability-spasticity-ectrodactyly syndrome 12.2
19 ectrodactyly and ectodermal dysplasia without cleft lip/palate 12.2
20 anonychia-onychodystrophy with brachydactyly type b and ectrodactyly 12.1
21 cleft palate, cardiac defect, genital anomalies, and ectrodactyly 12.1
22 ectrodactyly cardiopathy dysmorphism 12.1
23 ectrodactyly-cleft palate syndrome 12.1
24 tibial aplasia-ectrodactyly syndrome 12.1
25 hartsfield syndrome 12.1
26 ectrodactyly-polydactyly 12.0
27 anonychia-ectrodactyly 12.0
28 phocomelia-ectrodactyly, ear malformation, deafness, and sinus arrhythmia 12.0
29 phocomelia ectrodactyly deafness sinus arrhythmia 12.0
30 ectrodactyly of lower limbs, congenital heart defect, and micrognathia 11.9
31 cleft palate cardiac defect ectrodactyly 11.9
32 holoprosencephaly ectrodactyly cleft lip palate 11.9
33 hydrops ectrodactyly syndactyly 11.9
34 short stature monodactylous ectrodactyly cleft palate 11.9
35 tibial aplasia ectrodactyly hydrocephalus 11.9
36 adult syndrome 11.9
37 triphalangeal thumbs with brachyectrodactyly 11.8
38 limb-mammary syndrome 11.8
39 split-foot deformity with mandibulofacial dysostosis 11.6
40 brachydactyly-ectrodactyly with fibular aplasia or hypoplasia 11.5
41 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 11.5
42 kasznica carlson coppedge syndrome 11.5
43 acrofacial dysostosis 1, nager type 11.4
44 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1 11.3
45 fibular aplasia, tibial campomelia, and oligosyndactyly syndrome 11.3
46 microphthalmia, syndromic 8 11.3
47 split hand split foot malformation autosomal recessive 11.3
48 focal dermal hypoplasia 11.3
49 jones hersh yusk syndrome 11.2
50 saal bulas syndrome 11.2

Graphical network of the top 20 diseases related to Split Hand-Foot Malformation:



Diseases related to Split Hand-Foot Malformation

Symptoms & Phenotypes for Split Hand-Foot Malformation

MGI Mouse Phenotypes related to Split Hand-Foot Malformation:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.63 DLX5 FBXW4 FGFR1 MAP3K20 TP63 UBE2I
2 limbs/digits/tail MP:0005371 9.43 BHLHA9 DLX5 FBXW4 FGFR1 MAP3K20 TP63
3 no phenotypic analysis MP:0003012 9.02 FBXW4 FGFR1 TP63 UBE2I WNT10B

Drugs & Therapeutics for Split Hand-Foot Malformation

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Ability of a Molecule (Prima) to Restore Physiological Differentiation in Epithelium Expressing Gene p63 Recruiting NCT02896387

Search NIH Clinical Center for Split Hand-Foot Malformation

Cochrane evidence based reviews: ectrodactyly

Genetic Tests for Split Hand-Foot Malformation

Anatomical Context for Split Hand-Foot Malformation

MalaCards organs/tissues related to Split Hand-Foot Malformation:

41
Bone, Heart

Publications for Split Hand-Foot Malformation

Articles related to Split Hand-Foot Malformation:

(show top 50) (show all 66)
# Title Authors Year
1
Homozygous sequence variants in the WNT10B gene underlie split hand/foot malformation. ( 29384555 )
2018
2
17p13.3 genomic rearrangement in a Chinese family with split-hand/foot malformation with long bone deficiency: report of a complicated duplication with marked variation in phenotype. ( 29970136 )
2018
3
Split hand-foot malformation and a novel WNT10B mutation. ( 29427788 )
2018
4
Bilateral split hand foot malformation in siblings: Case series. ( 29499514 )
2018
5
Genetic regulatory pathways of split-hand/foot malformation. ( 30101460 )
2018
6
Insights into the pathogenesis and treatment of split hand foot malformation (cleft hand). ( 30380990 )
2018
7
Microduplications of 10q24 Detected in Two Chinese Patients with Split-hand/foot Malformation Type 3. ( 29263051 )
2017
8
Split hand/foot malformation: a potential clue to underlying FGFR1 mutation in patients with isolated congenital hypogonadotropic hypogonadism. ( 29146774 )
2017
9
A Novel Heterozygous Intragenic Sequence Variant in DLX6 Probably Underlies First Case of Autosomal Dominant Split-Hand/Foot Malformation Type 1. ( 28611547 )
2017
10
FGFR1 Analyses in Four Patients with Hypogonadotropic Hypogonadism with Split-Hand/Foot Malformation: Implications for the Promoter Region. ( 28087897 )
2017
11
Copy-number variants and candidate gene mutations in isolated split hand/foot malformation. ( 28539665 )
2017
12
Molecular Genetic Characterization of a Chinese Family with Severe Split Hand/Foot Malformation. ( 28422522 )
2017
13
A New Split Hand/Foot Malformation with Long Bone Deficiency Familial Case. ( 28496997 )
2017
14
A Novel Heterozygous Frameshift Mutation in DLX5 Gene Underlies Isolated Split Hand Foot Malformation type 1. ( 27085093 )
2016
15
Recurrence of split hand/foot malformation, cleft lip/palate, and severe urogenital abnormalities due to germline mosaicism for TP63 mutation. ( 27351625 )
2016
16
Split Hand/Foot Malformation Associated with 7q21.3 Microdeletion: A Case Report. ( 27022330 )
2016
17
Split Hand / Foot Malformation Syndrome with Cerebral Degeneration. ( 27730782 )
2016
18
Split hand/foot malformation genetics supports the chromosome 7 copy segregation mechanism for human limb development. ( 27821526 )
2016
19
Phenotypic subregions within the split-hand/foot malformation 1 locus. ( 26839112 )
2016
20
Selective chromatid segregation mechanism proposed for the human split hand/foot malformation development by chromosome 2 translocations: A perspective. ( 26477560 )
2015
21
Identification of Critical Region Responsible for Split Hand/Foot Malformation Type 3 (SHFM3) Phenotype through Systematic Review of Literature and Mapping of Breakpoints Using Microarray Data. ( 27600068 )
2015
22
Array comparative genomic hybridization characterization of multiple interstitial deletions involving 7p22.1, 7q11.23, 7q21.3-q22.1, 19p13.3-p12, and 19q13.11-q13.43 in a fetus associated with split hand-foot malformation. Role of EPS15L1 in pathogenesis. ( 26384072 )
2015
23
Heterozygous DLX5 nonsense mutation associated with isolated split-hand/foot malformation with reduced penetrance and variable expressivity in two unrelated families. ( 25196357 )
2014
24
Japanese founder duplications/triplications involving BHLHA9 are associated with split-hand/foot malformation with or without long bone deficiency and Gollop-Wolfgang complex. ( 25351291 )
2014
25
Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations. ( 25394172 )
2014
26
Split hand/foot malformation syndrome (SHFM): rare congenital orthopaedic disorder. ( 24973351 )
2014
27
Novel homozygous mutations in the WNT10B gene underlying autosomal recessive split hand/foot malformation in three consanguineous families. ( 24211389 )
2014
28
Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation. ( 24496061 )
2014
29
Split-hand/foot malformation - molecular cause and implications in genetic counseling. ( 24163146 )
2013
30
A rare case of split hand/foot malformation with sensorineural hearing loss and Mondini dysplasia. ( 23168687 )
2013
31
Split hand/foot malformation with long-bone deficiency and BHLHA9 duplication: report of 13 new families. ( 23790188 )
2013
32
Split-hand/foot malformation with long-bone deficiency and BHLHA9 duplication: two cases and expansion of the phenotype to radial agenesis. ( 23202277 )
2013
33
Clinical, genetic, and molecular aspects of split-hand/foot malformation: an update. ( 24115638 )
2013
34
Anorectal malformation associated with a mutation in the P63 gene in a family with split hand-foot malformation. ( 23736768 )
2013
35
A rare complex malformation of the hand in split hand foot malformation type 3 (SHFM3). ( 23722700 )
2013
36
A novel homozygous missense mutation in WNT10B in familial split-hand/foot malformation. ( 21554266 )
2012
37
A novel p63 mutation in a fetus with ultrasound detection of split hand/foot malformation. ( 22430731 )
2012
38
17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD). ( 21629300 )
2011
39
Homozygous nonsense mutation in WNT10B and sporadic split-hand/foot malformation (SHFM) with autosomal recessive inheritance. ( 20635353 )
2010
40
Distal limb deficiencies, micrognathia syndrome, and syndromic forms of split hand foot malformation (SHFM) are caused by chromosome 10q genomic rearrangements. ( 19584065 )
2010
41
Refinement of the Region for Split Hand/Foot Malformation 5 on 2q31.1. ( 22140379 )
2010
42
4q32-q35 and 6q16-q22 are valuable candidate regions for split hand/foot malformation. ( 19223930 )
2009
43
Split hand-foot malformation, tetralogy of Fallot, mental retardation and a 1 Mb 19p deletion-evidence for further heterogeneity? ( 19353584 )
2009
44
Split hand/foot malformation due to chromosome 7q aberrations(SHFM1): additional support for functional haploinsufficiency as the causative mechanism. ( 19401716 )
2009
45
Prenatal diagnosis of concomitant Wolf-Hirschhorn syndrome and split hand-foot malformation associated with partial monosomy 4p (4p16.1-->pter) and partial trisomy 10q (10q25.1-->qter). ( 18395879 )
2008
46
Split hand foot malformation with whorl-like pigmentary pattern: phenotypic expression of somatic mosaicism for the p63 mutation. ( 18792980 )
2008
47
The association of split hand foot malformation (SHFM) and congenital heart defects. ( 18383509 )
2008
48
A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1-17p13.3. ( 18493797 )
2008
49
Homozygous WNT10b mutation and complex inheritance in Split-Hand/Foot Malformation. ( 18515319 )
2008
50
Genomewide linkage scan for split-hand/foot malformation with long-bone deficiency in a large Arab family identifies two novel susceptibility loci on chromosomes 1q42.2-q43 and 6q14.1. ( 17160898 )
2007

Variations for Split Hand-Foot Malformation

Expression for Split Hand-Foot Malformation

Search GEO for disease gene expression data for Split Hand-Foot Malformation.

Pathways for Split Hand-Foot Malformation

Pathways related to Split Hand-Foot Malformation according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.94 DLX5 FGFR1 WNT10B

GO Terms for Split Hand-Foot Malformation

Biological processes related to Split Hand-Foot Malformation according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 9.76 FGFR1 TP63 UBE2I WNT10B
2 cell proliferation GO:0008283 9.7 DLX5 MAP3K20 TP63
3 multicellular organism development GO:0007275 9.65 BHLHA9 DLX5 FBXW4 TP63 WNT10B
4 epithelial cell differentiation GO:0030855 9.54 DLX5 TP63
5 inner ear morphogenesis GO:0042472 9.51 DLX5 FGFR1
6 positive regulation of osteoblast differentiation GO:0045669 9.49 TP63 WNT10B
7 embryonic digit morphogenesis GO:0042733 9.48 FBXW4 MAP3K20
8 limb development GO:0060173 9.43 FBXW4 MAP3K20
9 chondrocyte differentiation GO:0002062 9.4 FGFR1 WNT10B
10 positive regulation of mesenchymal cell proliferation GO:0002053 9.37 FBXW4 FGFR1
11 skeletal system development GO:0001501 9.33 DLX5 FGFR1 TP63
12 anatomical structure formation involved in morphogenesis GO:0048646 9.32 DLX5 TP63
13 ear development GO:0043583 8.96 DLX5 FGFR1
14 embryonic limb morphogenesis GO:0030326 8.92 DLX5 FBXW4 FGFR1 TP63

Sources for Split Hand-Foot Malformation

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....