MCID: SPL037
MIFTS: 41

Split Hand Foot Malformation malady

Genetic diseases, Rare diseases, Bone diseases, Fetal diseases categories

Summaries for Split Hand Foot Malformation

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NIH Rare Diseases:41 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 ectrodactyly, is related to split-hand/foot malformation 6 and rapp-hodgkin syndrome, and has symptoms including split hand, finger syndactyly and sensorineural hearing impairment. An important gene associated with Split Hand Foot Malformation is TP63 (tumor protein p63), and among its related pathways are beta-catenin independent WNT signaling and Hippo signaling pathway. Affiliated tissues include bone and heart, and related mouse phenotypes are taste/olfaction and limbs/digits/tail.

Aliases & Classifications for Split Hand Foot Malformation

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Sources:
41NIH Rare Diseases, 47Orphanet, 20GeneTests, 43Novoseek, 22GTR, 60UMLS, 26ICD10 via Orphanet, 61UMLS via Orphanet
See all sources

Split Hand Foot Malformation, Aliases & Descriptions:

Name: Split Hand Foot Malformation 41 47
Ectrodactyly 41 20 43 47 22 60
Split Hand-Split Foot Malformation 41 47
Lobster-Claw Deformity 41 47
Shfm 41 47
 
Split-Hand/foot Malformation 60
Split Hand Foot Deformity 1 60
Split Hand Foot Deformity 60
Absent Finger 60


Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases, Fetal diseases
Anatomical: Bone diseases


Characteristics (Orphanet epidemiological data):

47
ectrodactyly:
Inheritance: Autosomal dominant,Autosomal recessive,X-linked recessive; Prevalence: 1-9/100000 (Europe); Age of onset: Infancy,Neonatal


External Ids:

Orphanet47 2440
ICD10 via Orphanet26 Q71.6, Q72.7
UMLS via Orphanet61 C0265554

Related Diseases for Split Hand Foot Malformation

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Diseases in the Split Hand Foot Malformation family:

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

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

(show top 50)    (show all 135)
idRelated DiseaseScoreTop Affiliating Genes
1split-hand/foot malformation 631.3WNT10B
2rapp-hodgkin syndrome30.2TP63
3syndactyly29.8TP63, SHFM1, FBXW4
4split hand11.1
5ectodermal dysplasia10.8
6split-hand/foot malformation with long bone deficiency 110.8
7split-hand/foot malformation 510.7
8split-hand/foot malformation 410.7
9eec syndrome10.7
10split hand foot malformation 110.7
11split-hand/foot malformation with long bone deficiency 210.6
12split-hand/foot malformation 1 with sensorineural hearing loss10.6
13split-hand/foot malformation with long bone deficiency 310.6
14split hand/foot malformation x-linked10.6
15split-hand/foot malformation 310.6
16cleft lip10.5
17ectodermal dysplasia, ectrodactyly, and macular dystrophy10.4
18mental retardation spasticity ectrodactyly10.4
19mondini dysplasia10.4
20femur bifid with monodactylous ectrodactyly10.4
21fibular aplasia ectrodactyly10.4
22phocomelia-ectrodactyly ear malformation deafness and sinus arrhythmia10.4
23holoprosencephaly10.4
24hartsfield syndrome10.3
25ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 310.3
26wolf-hirschhorn syndrome10.3
27tetralogy of fallot10.3
28tibial hemimelia10.3
29hypogonadotropism10.3
30sensorineural hearing loss10.3
31hypogonadism10.3
32split hand split foot malformation autosomal recessive10.3
33mental retardation10.3
34anonychia-onychodystrophy with brachydactyly type b and ectrodactyly10.3
35anonychia ectrodactyly10.2
36ectrodactyly and ectodermal dysplasia without cleft lip/palate10.2
37ectrodactyly cardiopathy dysmorphism10.2
38ectrodactyly cleft palate syndrome10.2
39phocomelia ectrodactyly deafness sinus arrhythmia10.2
40adult syndrome10.2
41microphthalmia, syndromic 810.2
42microphthalmia10.2
43cleft palate cardiac defect ectrodactyly10.2
44ectrodactyly polydactyly10.2
45fibular aplasia10.2
46holoprosencephaly ectrodactyly cleft lip palate10.2
47hydrops ectrodactyly syndactyly10.2
48kasznica carlson coppedge syndrome10.2
49short stature monodactylous ectrodactyly cleft palate10.2
50tibial aplasia ectrodactyly hydrocephalus10.2

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



Diseases related to split hand foot malformation

Symptoms for Split Hand Foot Malformation

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Symptoms:

 47 (show all 9)
  • oligodactyly/ectrodactyly of fingers
  • autosomal dominant inheritance
  • syndactyly of fingers/interdigital palm
  • aniridia/iris hypoplasia
  • sensorineural deafness/hearing loss
  • hand agenesis/absence
  • trident hand/split hand/abnormal median ray
  • autosomal recessive inheritance
  • x-linked recessive inheritance

HPO human phenotypes related to Split Hand Foot Malformation:

(show all 6)
id Description Frequency HPO Source Accession
1 split hand hallmark (90%) HP:0001171
2 finger syndactyly typical (50%) HP:0006101
3 sensorineural hearing impairment occasional (7.5%) HP:0000407
4 split hand occasional (7.5%) HP:0001171
5 absent hand occasional (7.5%) HP:0004050
6 aplasia/hypoplasia of the iris occasional (7.5%) HP:0008053

Drugs & Therapeutics for Split Hand Foot Malformation

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Drug clinical trials:

Search ClinicalTrials for Split Hand Foot Malformation

Search NIH Clinical Center for Split Hand Foot Malformation

Genetic Tests for Split Hand Foot Malformation

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Genetic tests related to Split Hand Foot Malformation:

id Genetic test Affiliating Genes
1 Ectrodactyly20 22 TP63

Anatomical Context for Split Hand Foot Malformation

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MalaCards organs/tissues related to Split Hand Foot Malformation:

31
Bone, Heart

Animal Models for Split Hand Foot Malformation or affiliated genes

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MGI Mouse Phenotypes related to Split Hand Foot Malformation:

35
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053949.5DLX5, TP63
2MP:00053718.6DLX5, TP63, FBXW4

Publications for Split Hand Foot Malformation

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Articles related to Split Hand Foot Malformation:

(show all 46)
idTitleAuthorsYear
1
Split hand/foot malformations with microdeletions at chromosomes 7 and 19 detected using array comparative genomic hybridization. (25675931)
2015
2
Prenatally diagnosed fetal split-hand/foot malformations often accompany a spectrum of anomalies. (24371113)
2014
3
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
4
Heterozygous DLX5 nonsense mutation associated with isolated split-hand/foot malformation with reduced penetrance and variable expressivity in two unrelated families. (25196357)
2014
5
Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations. (25394172)
2014
6
Novel homozygous mutations in the WNT10B gene underlying autosomal recessive split hand/foot malformation in three consanguineous families. (24211389)
2014
7
Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation. (24496061)
2014
8
Split hand/foot malformation syndrome (SHFM): rare congenital orthopaedic disorder. (24973351)
2014
9
A rare complex malformation of the hand in split hand foot malformation type 3 (SHFM3). (23722700)
2013
10
Anorectal malformation associated with a mutation in the P63 gene in a family with split hand-foot malformation. (23736768)
2013
11
Split-hand/foot malformation - molecular cause and implications in genetic counseling. (24163146)
2013
12
Split-hand/foot malformation with long-bone deficiency and BHLHA9 duplication: two cases and expansion of the phenotype to radial agenesis. (23202277)
2013
13
Clinical, genetic, and molecular aspects of split-hand/foot malformation: an update. (24115638)
2013
14
Split hand/foot malformation with long-bone deficiency and BHLHA9 duplication: report of 13 new families. (23790188)
2013
15
A rare case of split hand/foot malformation with sensorineural hearing loss and Mondini dysplasia. (23168687)
2013
16
A novel homozygous missense mutation in WNT10B in familial split-hand/foot malformation. (21554266)
2012
17
A novel p63 mutation in a fetus with ultrasound detection of split hand/foot malformation. (22430731)
2012
18
17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD). (21629300)
2011
19
Homozygous nonsense mutation in WNT10B and sporadic split-hand/foot malformation (SHFM) with autosomal recessive inheritance. (20635353)
2010
20
Refinement of the Region for Split Hand/Foot Malformation 5 on 2q31.1. (22140379)
2010
21
Distal limb deficiencies, micrognathia syndrome, and syndromic forms of split hand foot malformation (SHFM) are caused by chromosome 10q genomic rearrangements. (19584065)
2010
22
Split hand/foot malformation due to chromosome 7q aberrations(SHFM1): additional support for functional haploinsufficiency as the causative mechanism. (19401716)
2009
23
4q32-q35 and 6q16-q22 are valuable candidate regions for split hand/foot malformation. (19223930)
2009
24
Split hand-foot malformation, tetralogy of Fallot, mental retardation and a 1 Mb 19p deletion-evidence for further heterogeneity? (19353584)
2009
25
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
26
Homozygous WNT10b mutation and complex inheritance in Split-Hand/Foot Malformation. (18515319)
2008
27
A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1-17p13.3. (18493797)
2008
28
The association of split hand foot malformation (SHFM) and congenital heart defects. (18383509)
2008
29
Split hand foot malformation with whorl-like pigmentary pattern: phenotypic expression of somatic mosaicism for the p63 mutation. (18792980)
2008
30
A new locus for split hand/foot malformation with long bone deficiency (SHFLD) at 2q14.2 identified from a chromosome translocation. (17569090)
2007
31
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
32
Evidence for an additional locus for split hand/foot malformation in chromosome region 8q21.11-q22.3. (16838310)
2006
33
Frequency of genomic rearrangements involving the SHFM3 locus at chromosome 10q24 in syndromic and non-syndromic split-hand/foot malformation. (16761290)
2006
34
Genotype-phenotype correlations in mapped split hand foot malformation (SHFM) patients. (16688749)
2006
35
Clinical and epidemiological findings in patients with central ray deficiency: split hand foot malformation (SHFM) in Manitoba, Canada. (16673359)
2006
36
The expanding panorama of split hand foot malformation. (16763964)
2006
37
Increased nuchal translucency and split-hand/foot malformation in a fetus with an interstitial deletion of chromosome 2q that removes the SHFM5 locus. (15662696)
2005
38
Discrepancies in upper and lower limb patterning in split hand foot malformation. (16207208)
2005
39
Split hand foot malformation (SHFM). (16283879)
2005
40
Altered sumoylation of p63alpha contributes to the split-hand/foot malformation phenotype. (15539951)
2004
41
Refinement of the deletion in 7q21.3 associated with split hand/foot malformation type 1 and Mondini dysplasia. (15121782)
2004
42
P63 mutations are not a major cause of non-syndromic split hand/foot malformation. (12525544)
2003
43
Split hand foot malformation is associated with a reduced level of Dactylin gene expression. (12974740)
2003
44
Mouse model of split hand/foot malformation type I. (12112878)
2002
45
Split hand-foot malformation: a congenital central limb ray deficiency. (12432199)
2002
46
Bilateral split hand/foot malformation and inv(7)(p22q21.3). (7616545)
1995

Variations for Split Hand Foot Malformation

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Clinvar genetic disease variations for Split Hand Foot Malformation:

6
id Gene Variation Type Significance SNP ID Assembly Location
1WNT10BWNT10B, 4-BP DUP, 458AGCAduplicationPathogenic
2TP63NM_003722.4(TP63): c.697A> G (p.Lys233Glu)single nucleotide variantPathogenicrs121908838GRCh37Chr 3, 189582138: 189582138
3TP63NM_003722.4(TP63): c.955C> T (p.Arg319Cys)single nucleotide variantPathogenicrs121908839GRCh37Chr 3, 189585694: 189585694
4TP63NM_003722.4(TP63): c.289C> T (p.Arg97Cys)single nucleotide variantPathogenicrs121908848GRCh37Chr 3, 189456528: 189456528
5WNT10BNM_003394.3(WNT10B): c.994C> T (p.Arg332Trp)single nucleotide variantPathogenicrs121918349GRCh37Chr 12, 49360054: 49360054

Expression for genes affiliated with Split Hand Foot Malformation

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

Pathways for genes affiliated with Split Hand Foot Malformation

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

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.2BTRC, WNT10B
29.2BTRC, WNT10B
39.2BTRC, WNT10B
4
Show member pathways
9.2BTRC, WNT10B

Compounds for genes affiliated with Split Hand Foot Malformation

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GO Terms for genes affiliated with Split Hand Foot Malformation

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

idNameGO IDScoreTop Affiliating Genes
1nuclear chromatinGO:00007909.5DLX5, TP63

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

(show all 9)
idNameGO IDScoreTop Affiliating Genes
1positive regulation of canonical Wnt signaling pathwayGO:00902639.6WNT10B, DLX5
2positive regulation of mesenchymal cell proliferationGO:00020539.6TP63, FBXW4
3skeletal system developmentGO:00015019.4TP63, DLX5
4positive regulation of osteoblast differentiationGO:00456699.3DLX5, WNT10B, TP63
5embryonic limb morphogenesisGO:00303269.1DLX5, TP63, FBXW4
6ubiquitin-dependent protein catabolic processGO:00065119.0BTRC, FBXW4
7G2/M transition of mitotic cell cycleGO:00000868.9BTRC, WNT10B
8positive regulation of transcription, DNA-templatedGO:00458938.7BTRC, DLX5, TP63
9Wnt signaling pathwayGO:00160558.7FBXW4, WNT10B, BTRC

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

idNameGO IDScoreTop Affiliating Genes
1transcription regulatory region DNA bindingGO:00442129.5DLX5, TP63
2RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcriptionGO:00010779.2DLX5, TP63

Products for genes affiliated with Split Hand Foot Malformation

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  • Antibodies
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Sources for Split Hand Foot Malformation

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
33MeSH
34MESH via Orphanet
35MGI
38NCIt
39NDF-RT
42NINDS
43Novoseek
45OMIM
46OMIM via Orphanet
50PubMed
51QIAGEN
56SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet