MCID: SPL061
MIFTS: 41

Split Hand-Foot Malformation

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

Aliases & Classifications for Split Hand-Foot Malformation

MalaCards integrated aliases for Split Hand-Foot Malformation:

Name: Split Hand-Foot Malformation 12 14
Split-Hand/foot Malformation 36 69
Ectrodactyly 49 69
Split Hand Foot Malformation 49
Split Hand Foot Deformity 1 69
Split Hand Foot Deformity 69
Lobster-Claw Deformity 12
Split-Hand Deformity 12
Shfm 49

Classifications:



External Ids:

Disease Ontology 12 DOID:0090020
ICD10 32 Q71.6
KEGG 36 H00471

Summaries for Split Hand-Foot Malformation

NIH Rare Diseases : 49 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. Last updated: 1/22/2014

MalaCards based summary : Split Hand-Foot Malformation, also known as split-hand/foot malformation, is related to split-hand/foot malformation 1 and split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive. An important gene associated with Split Hand-Foot Malformation is SHFM2 (Split Hand/Foot Malformation (Ectrodactyly) Type 2), and among its related pathways/superpathways are Signaling pathways regulating pluripotency of stem cells and Development_Glucocorticoid receptor signaling. Affiliated tissues include bone and heart, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

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 all 45)
# Related Disease Score Top Affiliating Genes
1 split-hand/foot malformation 1 34.3 DLX5 SEM1 TP63
2 split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive 34.3 DLX5 SEM1
3 split-hand/foot malformation 3 33.6 DLX5 FBXW4 SEM1 TP63 WNT10B
4 split-hand/foot malformation 4 33.4 DLX5 FBXW4 SEM1 TP63 WNT10B
5 split-hand/foot malformation 6 33.2 BHLHA9 DLX5 FBXW4 SEM1 TP63 WNT10B
6 split-hand/foot malformation 5 33.1 DLX5 FBXW4 SEM1 SHFM5 TP63 WNT10B
7 split-hand/foot malformation 2 33.0 DLX5 FBXW4 SEM1 SHFM2 TP63 WNT10B
8 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1 32.2 TP63 WNT10B
9 split hand-split foot malformation 31.2 DLX5 FBXW4 SEM1 SHFM2 TP63 WNT10B
10 split hand 30.4 BHLHA9 DLX5 FBXW4 SEM1 TP63 WNT10B
11 cleft lip 29.2 FGFR1 SUMO1 TP63
12 split-hand/foot malformation with long bone deficiency 1 12.6
13 split hand/foot malformation x-linked 12.6
14 ulnar hypoplasia with lobster-claw deformity of feet 12.5
15 split-hand/foot malformation with long bone deficiency 2 12.4
16 chromosome 17p13.3, telomeric, duplication syndrome 12.2
17 tibial aplasia-ectrodactyly syndrome 11.9
18 brachydactyly-ectrodactyly with fibular aplasia or hypoplasia 11.4
19 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 11.4
20 fibular aplasia, tibial campomelia, and oligosyndactyly syndrome 11.2
21 microphthalmia, syndromic 8 11.2
22 split hand split foot malformation autosomal recessive 11.2
23 hypogonadotropic hypogonadism 10.2
24 hypogonadism 10.2
25 hypogonadotropism 10.2
26 paranoid personality disorder 10.2 DLX5 SEM1
27 mondini dysplasia 10.2
28 rapp-hodgkin syndrome 10.0 DLX5 SEM1 TP63
29 tetralogy of fallot 10.0
30 wolf-hirschhorn syndrome 10.0
31 femur, unilateral bifid, with monodactylous ectrodactyly 10.0
32 tibial hemimelia 10.0
33 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
34 sensorineural hearing loss 10.0
35 heart disease 10.0
36 cerebral degeneration 10.0
37 cerebritis 10.0
38 chromosome 10q duplication 10.0
39 chromosome 19p deletion 10.0
40 femur bifid with monodactylous ectrodactyly 10.0
41 cleft lip/palate 10.0
42 lacrimoauriculodentodigital syndrome 9.8 FGFR1 TP63
43 split foot 9.5 DLX5 FBXW4 SEM1 SHFM2 TP63
44 tooth agenesis 9.3 FGFR1 SUMO1 WNT10B
45 orofacial cleft 9.3 DLX5 FGFR1 SUMO1 TP63

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

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

25 (show all 25)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-100 9.78 HAND2 FGFR1
2 Increased shRNA abundance (Z-score > 2) GR00366-A-118 9.78 HAND2
3 Increased shRNA abundance (Z-score > 2) GR00366-A-125 9.78 FGFR1
4 Increased shRNA abundance (Z-score > 2) GR00366-A-126 9.78 FGFR1 HAND2 UBE2I
5 Increased shRNA abundance (Z-score > 2) GR00366-A-13 9.78 UBE2I
6 Increased shRNA abundance (Z-score > 2) GR00366-A-146 9.78 HAND2
7 Increased shRNA abundance (Z-score > 2) GR00366-A-152 9.78 UBE2I
8 Increased shRNA abundance (Z-score > 2) GR00366-A-157 9.78 UBE2I
9 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.78 UBE2I
10 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.78 FGFR1
11 Increased shRNA abundance (Z-score > 2) GR00366-A-176 9.78 HAND2
12 Increased shRNA abundance (Z-score > 2) GR00366-A-183 9.78 FGFR1
13 Increased shRNA abundance (Z-score > 2) GR00366-A-197 9.78 HAND2
14 Increased shRNA abundance (Z-score > 2) GR00366-A-3 9.78 UBE2I
15 Increased shRNA abundance (Z-score > 2) GR00366-A-31 9.78 HAND2
16 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.78 HAND2
17 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.78 HAND2 FGFR1
18 Increased shRNA abundance (Z-score > 2) GR00366-A-47 9.78 FGFR1
19 Increased shRNA abundance (Z-score > 2) GR00366-A-50 9.78 FGFR1
20 Increased shRNA abundance (Z-score > 2) GR00366-A-52 9.78 UBE2I
21 Increased shRNA abundance (Z-score > 2) GR00366-A-57 9.78 UBE2I
22 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.78 FGFR1
23 Increased shRNA abundance (Z-score > 2) GR00366-A-79 9.78 UBE2I
24 Increased shRNA abundance (Z-score > 2) GR00366-A-83 9.78 FGFR1
25 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.78 HAND2

MGI Mouse Phenotypes related to Split Hand-Foot Malformation:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.65 DLX5 FGFR1 HAND2 SUMO1 TP63
2 embryo MP:0005380 9.63 DLX5 FBXW4 FGFR1 HAND2 TP63 UBE2I
3 limbs/digits/tail MP:0005371 9.43 BHLHA9 DLX5 FBXW4 FGFR1 HAND2 TP63
4 no phenotypic analysis MP:0003012 9.1 FGFR1 HAND2 TP63 UBE2I WNT10B FBXW4

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

Genetic Tests for Split Hand-Foot Malformation

Anatomical Context for Split Hand-Foot Malformation

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

38
Bone, Heart

Publications for Split Hand-Foot Malformation

Articles related to Split Hand-Foot Malformation:

(show top 50) (show all 64)
# Title Authors Year
1
Split hand-foot malformation and a novel WNT10B mutation. ( 29427788 )
2018
2
Homozygous sequence variants in the WNT10B gene underlie split hand/foot malformation. ( 29384555 )
2018
3
Microduplications of 10q24 Detected in Two Chinese Patients with Split-hand/foot Malformation Type 3. ( 29263051 )
2017
4
A Novel Heterozygous Intragenic Sequence Variant in DLX6 Probably Underlies First Case of Autosomal Dominant Split-Hand/Foot Malformation Type 1. ( 28611547 )
2017
5
Copy-number variants and candidate gene mutations in isolated split hand/foot malformation. ( 28539665 )
2017
6
Split hand/foot malformation: a potential clue to underlying FGFR1 mutation in patients with isolated congenital hypogonadotropic hypogonadism. ( 29146774 )
2017
7
Molecular Genetic Characterization of a Chinese Family with Severe Split Hand/Foot Malformation. ( 28422522 )
2017
8
A New Split Hand/Foot Malformation with Long Bone Deficiency Familial Case. ( 28496997 )
2017
9
FGFR1 Analyses in Four Patients with Hypogonadotropic Hypogonadism with Split-Hand/Foot Malformation: Implications for the Promoter Region. ( 28087897 )
2017
10
Split Hand/Foot Malformation Associated with 7q21.3 Microdeletion: A Case Report. ( 27022330 )
2016
11
A Novel Heterozygous Frameshift Mutation in DLX5 Gene Underlies Isolated Split Hand Foot Malformation type 1. ( 27085093 )
2016
12
Recurrence of split hand/foot malformation, cleft lip/palate, and severe urogenital abnormalities due to germline mosaicism for TP63 mutation. ( 27351625 )
2016
13
Phenotypic subregions within the split-hand/foot malformation 1 locus. ( 26839112 )
2016
14
Split Hand / Foot Malformation Syndrome with Cerebral Degeneration. ( 27730782 )
2016
15
Split hand/foot malformation genetics supports the chromosome 7 copy segregation mechanism for human limb development. ( 27821526 )
2016
16
Split hand/foot malformations with microdeletions at chromosomes 7 and 19 detected using array comparative genomic hybridization. ( 25675931 )
2015
17
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
18
Selective chromatid segregation mechanism proposed for the human split hand/foot malformation development by chromosome 2 translocations: A perspective. ( 26477560 )
2015
19
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
20
Prenatally diagnosed fetal split-hand/foot malformations often accompany a spectrum of anomalies. ( 24371113 )
2014
21
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
22
Novel homozygous mutations in the WNT10B gene underlying autosomal recessive split hand/foot malformation in three consanguineous families. ( 24211389 )
2014
23
Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations. ( 25394172 )
2014
24
Heterozygous DLX5 nonsense mutation associated with isolated split-hand/foot malformation with reduced penetrance and variable expressivity in two unrelated families. ( 25196357 )
2014
25
Split hand/foot malformation syndrome (SHFM): rare congenital orthopaedic disorder. ( 24973351 )
2014
26
Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation. ( 24496061 )
2014
27
Clinical, genetic, and molecular aspects of split-hand/foot malformation: an update. ( 24115638 )
2013
28
Split-hand/foot malformation with long-bone deficiency and BHLHA9 duplication: two cases and expansion of the phenotype to radial agenesis. ( 23202277 )
2013
29
Split-hand/foot malformation - molecular cause and implications in genetic counseling. ( 24163146 )
2013
30
Split hand/foot malformation with long-bone deficiency and BHLHA9 duplication: report of 13 new families. ( 23790188 )
2013
31
Anorectal malformation associated with a mutation in the P63 gene in a family with split hand-foot malformation. ( 23736768 )
2013
32
A rare case of split hand/foot malformation with sensorineural hearing loss and Mondini dysplasia. ( 23168687 )
2013
33
A rare complex malformation of the hand in split hand foot malformation type 3 (SHFM3). ( 23722700 )
2013
34
A novel p63 mutation in a fetus with ultrasound detection of split hand/foot malformation. ( 22430731 )
2012
35
A novel homozygous missense mutation in WNT10B in familial split-hand/foot malformation. ( 21554266 )
2012
36
17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD). ( 21629300 )
2011
37
Homozygous nonsense mutation in WNT10B and sporadic split-hand/foot malformation (SHFM) with autosomal recessive inheritance. ( 20635353 )
2010
38
Distal limb deficiencies, micrognathia syndrome, and syndromic forms of split hand foot malformation (SHFM) are caused by chromosome 10q genomic rearrangements. ( 19584065 )
2010
39
Refinement of the Region for Split Hand/Foot Malformation 5 on 2q31.1. ( 22140379 )
2010
40
4q32-q35 and 6q16-q22 are valuable candidate regions for split hand/foot malformation. ( 19223930 )
2009
41
Split hand/foot malformation due to chromosome 7q aberrations(SHFM1): additional support for functional haploinsufficiency as the causative mechanism. ( 19401716 )
2009
42
Split hand-foot malformation, tetralogy of Fallot, mental retardation and a 1 Mb 19p deletion-evidence for further heterogeneity? ( 19353584 )
2009
43
Split hand foot malformation with whorl-like pigmentary pattern: phenotypic expression of somatic mosaicism for the p63 mutation. ( 18792980 )
2008
44
The association of split hand foot malformation (SHFM) and congenital heart defects. ( 18383509 )
2008
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
A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1-17p13.3. ( 18493797 )
2008
47
Homozygous WNT10b mutation and complex inheritance in Split-Hand/Foot Malformation. ( 18515319 )
2008
48
A new locus for split hand/foot malformation with long bone deficiency (SHFLD) at 2q14.2 identified from a chromosome translocation. ( 17569090 )
2007
49
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
50
Clinical and epidemiological findings in patients with central ray deficiency: split hand foot malformation (SHFM) in Manitoba, Canada. ( 16673359 )
2006

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

GO Terms for Split Hand-Foot Malformation

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

# Name GO ID Score Top Affiliating Genes
1 nuclear chromatin GO:0000790 8.8 DLX5 HAND2 TP63

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

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 9.72 FGFR1 SUMO1 TP63 UBE2I WNT10B
2 skeletal system development GO:0001501 9.63 DLX5 FGFR1 TP63
3 multicellular organism development GO:0007275 9.63 BHLHA9 DLX5 FBXW4 HAND2 TP63 WNT10B
4 positive regulation of canonical Wnt signaling pathway GO:0090263 9.58 DLX5 SEM1 WNT10B
5 chondrocyte differentiation GO:0002062 9.51 FGFR1 WNT10B
6 global genome nucleotide-excision repair GO:0070911 9.49 SUMO1 UBE2I
7 negative regulation of DNA binding GO:0043392 9.48 HAND2 SUMO1
8 anatomical structure formation involved in morphogenesis GO:0048646 9.43 DLX5 TP63
9 palate development GO:0060021 9.43 DLX5 HAND2 SUMO1
10 sympathetic nervous system development GO:0048485 9.37 HAND2 TP63
11 positive regulation of mesenchymal cell proliferation GO:0002053 9.13 FBXW4 FGFR1 TP63
12 embryonic limb morphogenesis GO:0030326 8.92 DLX5 FBXW4 FGFR1 TP63

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

# Name GO ID Score Top Affiliating Genes
1 transcription regulatory region DNA binding GO:0044212 9.33 DLX5 HAND2 TP63
2 SUMO transferase activity GO:0019789 8.96 SUMO1 UBE2I
3 small protein activating enzyme binding GO:0044388 8.62 SUMO1 UBE2I

Sources for Split Hand-Foot Malformation

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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