SHFM1
MCID: SPL067
MIFTS: 46

Split-Hand/foot Malformation 1 (SHFM1)

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

Aliases & Classifications for Split-Hand/foot Malformation 1

MalaCards integrated aliases for Split-Hand/foot Malformation 1:

Name: Split-Hand/foot Malformation 1 56 29 6
Ectrodactyly 56 74 29 54 6 71
Split Hand-Foot Malformation 1 12 15
Split-Hand Deformity 56 74
Shfm1 56 12
Shfd1 56 12
Split-Hand/foot Malformation 1 with or Without Deafness 56
Split-Hand/foot Deformity 1; Shfd1; Shsf1 56
Split Hand/foot Malformation 1 13
Split-Hand/foot Malformation 71
Split-Hand/foot Deformity 1 56
Split Hand Foot Deformity 1 71
Ectrodactyly; Ecd 56
Ecd 56

Characteristics:

OMIM:

56
Miscellaneous:
variable expressivity
incomplete penetrance
contiguous gene syndrome caused by deletion, duplication, or rearrangement of chromosome 7q21.3 involving the dss1 , dlx5 , and dlx6 genes and possible regulatory elements in the region

Inheritance:
autosomal dominant


HPO:

31
split-hand/foot malformation 1:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity incomplete penetrance


Classifications:



Summaries for Split-Hand/foot Malformation 1

OMIM : 56 Split-hand/foot malformation (SHFM) is a limb malformation involving 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 with SHFM1 have been found to have mental retardation, ectodermal and craniofacial findings, orofacial clefting (Elliott and Evans, 2006), and neurosensory hearing loss (Tackels-Horne et al., 2001). (183600)

MalaCards based summary : Split-Hand/foot Malformation 1, also known as ectrodactyly, is related to split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive and ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3. An important gene associated with Split-Hand/foot Malformation 1 is DLX5 (Distal-Less Homeobox 5). Affiliated tissues include bone, skin and heart, and related phenotypes are split hand and split foot

Disease Ontology : 12 A split-hand/foot malformation that has material basis in contiguous gene mutations caused by deletion, duplication, or rearrangement of chromosome 7q21.3 involving the DSS1, DLX5, and DLX6 genes and possible regulatory elements in the region.

Wikipedia : 74 Ectrodactyly, split hand, cleft hand, derived from the Greek ektroma (abortion) and daktylos (finger)... more...

Related Diseases for Split-Hand/foot Malformation 1

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 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 365)
# Related Disease Score Top Affiliating Genes
1 split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive 34.6 TP63 DLX5
2 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 34.0 TP63 DLX5
3 split-hand/foot malformation 3 31.9 TP63 DLX5
4 split-hand/foot malformation 6 31.8 TP63 DLX5
5 split-hand/foot malformation 4 31.8 TP63 DLX5
6 ankyloblepharon-ectodermal defects-cleft lip/palate 31.5 TP63 DLX5
7 split-hand/foot malformation 2 31.5 TP63 SHFM2 DLX5
8 split-hand/foot malformation 5 31.5 TP63 SHFM5 DLX5
9 isolated split hand-split foot malformation 30.8 TP63 DLX5
10 rapp-hodgkin syndrome 29.9 TP63 DLX5
11 chromosome 2q35 duplication syndrome 29.7 TP63 DLX5
12 split hand-foot malformation 29.6 TP63 SHFM5 SHFM2 DLX5
13 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1 12.7
14 ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome 12.7
15 cleft palate, cardiac defect, genital anomalies, and ectrodactyly 12.6
16 brachydactyly-ectrodactyly with fibular aplasia or hypoplasia 12.6
17 femur bifid with monodactylous ectrodactyly 12.5
18 ectrodactyly and ectodermal dysplasia without cleft lip/palate 12.5
19 intellectual disability-spasticity-ectrodactyly syndrome 12.4
20 erdheim-chester disease 12.4
21 ectrodactyly-polydactyly 12.3
22 hartsfield syndrome 12.3
23 femur, unilateral bifid, with monodactylous ectrodactyly 12.3
24 anonychia-ectrodactyly 12.3
25 anonychia-onychodystrophy with brachydactyly type b and ectrodactyly 12.3
26 ectrodactyly cardiopathy dysmorphism 12.3
27 ectrodactyly-cleft palate syndrome 12.3
28 tibial aplasia-ectrodactyly syndrome 12.3
29 microphthalmia, syndromic 8 12.2
30 ectrodactyly of lower limbs, congenital heart defect, and micrognathia 12.2
31 phocomelia-ectrodactyly, ear malformation, deafness, and sinus arrhythmia 12.2
32 phocomelia ectrodactyly deafness sinus arrhythmia 12.1
33 adult syndrome 12.1
34 ectrodactyly with and without other manifestations 12.1
35 limb-mammary syndrome 12.0
36 atrioventricular septal defect 12.0
37 triphalangeal thumbs with brachyectrodactyly 12.0
38 split-foot deformity with mandibulofacial dysostosis 12.0
39 focal dermal hypoplasia 11.7
40 acrofacial dysostosis 1, nager type 11.6
41 hemifacial atrophy, progressive 11.6
42 limb defects, distal transverse, with mental retardation and spasticity 11.6
43 kasznica carlson coppedge syndrome 11.6
44 adams-oliver syndrome 1 11.4
45 jones hersh yusk syndrome 11.4
46 landy-donnai syndrome 11.4
47 saal bulas syndrome 11.4
48 split-hand with congenital nystagmus, fundal changes, and cataracts 11.3
49 split hand split foot malformation autosomal recessive 11.2
50 split hand/foot malformation x-linked 11.2

Graphical network of the top 20 diseases related to Split-Hand/foot Malformation 1:



Diseases related to Split-Hand/foot Malformation 1

Symptoms & Phenotypes for Split-Hand/foot Malformation 1

Human phenotypes related to Split-Hand/foot Malformation 1:

31 (show all 21)
# Description HPO Frequency HPO Source Accession
1 split hand 31 hallmark (90%) HP:0001171
2 split foot 31 hallmark (90%) HP:0001839
3 cleft palate 31 frequent (33%) HP:0000175
4 hand oligodactyly 31 frequent (33%) HP:0001180
5 foot oligodactyly 31 frequent (33%) HP:0001849
6 syndactyly 31 frequent (33%) HP:0001159
7 hearing impairment 31 very rare (1%) HP:0000365
8 intellectual disability 31 very rare (1%) HP:0001249
9 abnormality of cardiovascular system morphology 31 very rare (1%) HP:0030680
10 abnormality of the pinna 31 very rare (1%) HP:0000377
11 sensorineural hearing impairment 31 HP:0000407
12 abnormality of the genital system 31 HP:0000078
13 abnormality of the urinary system 31 HP:0000079
14 cutaneous finger syndactyly 31 HP:0010554
15 triphalangeal thumb 31 HP:0001199
16 median cleft lip 31 HP:0000161
17 ectrodactyly 31 HP:0100257
18 lacrimal duct aplasia 31 HP:0007925
19 2-3 toe syndactyly 31 HP:0004691
20 clinodactyly 31 HP:0030084
21 broad hallux 31 HP:0010055

Symptoms via clinical synopsis from OMIM:

56
Skeletal Hands:
split hand
ectrodactyly
triphalangeal thumbs
aplasia of single digital ray
hypoplasia, fusion, and contractures of post-axial fingers

Skeletal Feet:
ectrodactyly
split foot
clinodactyly
broad hallux

Clinical features from OMIM:

183600

Drugs & Therapeutics for Split-Hand/foot Malformation 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Ex Vivo and in Vitro Assessment of the Pharmacological Properties of Molecule Prima in the Restoration of Physiological Differentiation of Gene p63 Dependant Epithelium Recruiting NCT02896387

Search NIH Clinical Center for Split-Hand/foot Malformation 1

Genetic Tests for Split-Hand/foot Malformation 1

Genetic tests related to Split-Hand/foot Malformation 1:

# Genetic test Affiliating Genes
1 Split-Hand/foot Malformation 1 29 DLX5
2 Ectrodactyly 29

Anatomical Context for Split-Hand/foot Malformation 1

MalaCards organs/tissues related to Split-Hand/foot Malformation 1:

40
Bone, Skin, Heart, Tongue, Eye, Breast, T Cells

Publications for Split-Hand/foot Malformation 1

Articles related to Split-Hand/foot Malformation 1:

(show top 50) (show all 726)
# Title Authors PMID Year
1
Heterozygous DLX5 nonsense mutation associated with isolated split-hand/foot malformation with reduced penetrance and variable expressivity in two unrelated families. 56 6 61
25196357 2014
2
Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation. 61 56 6
24496061 2014
3
Characterization of the complex 7q21.3 rearrangement in a patient with bilateral split-foot malformation and hearing loss. 61 56
19449426 2009
4
Complex rearrangement of chromosomes 7q21.13-q22.1 confirms the ectrodactyly-deafness locus and suggests new candidate genes. 61 56
18080328 2008
5
Genotype-phenotype correlations in mapped split hand foot malformation (SHFM) patients. 61 56
16688749 2006
6
Pathogenesis of split-hand/split-foot malformation. 61 56
12668597 2003
7
Mouse model of split hand/foot malformation type I. 61 56
12112878 2002
8
Mapping the mouse dactylaplasia mutation, Dac, and a gene that controls its expression, mdac. 61 56
8666395 1995
9
Ectrodactyly and proximal/intermediate interstitial deletion 7q. 61 56
7747769 1995
10
Split foot and developmental retardation associated with a deletion of three microsatellite markers in 7q21.2-q22.1. 56 61
7606850 1995
11
Physical mapping of the split hand/split foot locus on chromosome 7 and implication in syndromic ectrodactyly. 61 56
7987313 1994
12
Evidence for locus heterogeneity in human autosomal dominant split hand/split foot malformation. 61 56
7912888 1994
13
Inverted insertion of chromosome 7q and ectrodactyly. 56 61
8322806 1993
14
Ectrodactyly of hands and feet in a child with a complex translocation including 7q21.2. 56 61
1877619 1991
15
Ectro-amelia syndrome associated with an interstitial deletion of 7q. 56 61
2301476 1990
16
Interstitial long-arm deletion of chromosome 7 and ectrodactyly. 61 56
2929660 1989
17
The split-hand and split-foot anomaly in a central African Negro population. 61 56
6507501 1984
18
Monodactylous splithand-splitfoot. A malformation occurring in three distinct genetic types. 56 61
7389732 1980
19
Dominant ectrodactyly and possible germinal mosaicism. 61 56
5079103 1972
20
A recessive form of ectrodactyly, and its implications in genetic counseling. 61 56
5094721 1971
21
Ectrodactyly--evidence in favour of a disturbed segregation in the offspring of affected males. 56 61
13834546 1960
22
Two pedigrees of ectrodactyly. 56 61
24541402 1951
23
Absent expression of the osteoblast-specific maternally imprinted genes, DLX5 and DLX6, causes split hand/split foot malformation type I. 56
25332435 2014
24
A 0.7 Mb de novo duplication at 7q21.3 including the genes DLX5 and DLX6 in a patient with split-hand/split-foot malformation. 56
23169702 2012
25
Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation. 56
22121204 2012
26
Discrepancies in upper and lower limb patterning in split hand foot malformation. 56
16207208 2005
27
Refinement of the deletion in 7q21.3 associated with split hand/foot malformation type 1 and Mondini dysplasia. 56
15121782 2004
28
Split hand/split foot malformation associated with sensorineural deafness, inner and middle ear malformation, hypodontia, congenital vertical talus, and deletion of eight microsatellite markers in 7q21.1-q21.3. 56
11424924 2001
29
Further evidence for germinal mosaicism in cleft hand/cleft foot syndrome. Two affected halfsisters and normal father. 56
11693788 2001
30
Split hand/split foot malformation with hearing loss: first report of families linked to the SHFM1 locus in 7q21. 56
11168022 2001
31
Defect in the maintenance of the apical ectodermal ridge in the Dactylaplasia mouse. 56
9733575 1998
32
Bilateral split hand/foot malformation and inv(7)(p22q21.3). 56
7616545 1995
33
Non-Mendelian transmission in a human developmental disorder: split hand/split foot. 56
7942849 1994
34
On the inheritance of the split hand/split foot malformation. 56
7802032 1994
35
Fine mapping of the autosomal dominant split hand/split foot locus on chromosome 7, band q21.3-q22.1. 56
8023840 1994
36
The genetics of human limb development. 56
7912883 1994
37
Split hand/split foot anomaly in a family segregating a balanced translocation with breakpoint on 7q22.1. 56
8279479 1993
38
Human situs determination and chromosome constitution 46,XY,ins(7;8)(q22;q12q24) 56
8192752 1993
39
Bilateral split hand and split foot malformation in a boy with a de novo interstitial deletion of 7q21.3. 56
1895319 1991
40
Why is Mendelian segregation so exact? 56
1909864 1991
41
[Interstitial deletion of the long arm of chromosome 7 and its clinical correlations]. 56
6680429 1983
42
A problem for genetic counselling - split hand deformity. 56
891014 1977
43
Another case of split-foot mutation in two sibs. 56
4320415 1970
44
[Split hand and foot with familial occurrence]. 56
14479171 1962
45
[Delayed mutation in man; a critical observation on the work of Ch. Auerbachs (1956)]. 56
13509525 1958
46
A possible case of delayed mutation in man. 56
13314396 1956
47
Molecular basis of EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: five new mutations in the DNA-binding domain of the TP63 gene and genotype-phenotype correlation. 61 54
19903181 2010
48
A 19-year follow-up of a patient with type 3 ectrodactyly-ectodermal dysplasia-clefting syndrome who developed non-Hodgkin lymphoma. 61 54
19716498 2009
49
A new mutation in TP63 is associated with age-related pathology. 54 61
17609671 2007
50
Further phenotypic and genetic variation in ADULT syndrome. 61 54
17041931 2006

Variations for Split-Hand/foot Malformation 1

ClinVar genetic disease variations for Split-Hand/foot Malformation 1:

6 (show all 22) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 subset of 67 genes: SGCE , TRRAP GRCh37/hg19 7q21.2-22.1(chr7:92445452-99686985)x1copy number loss Pathogenic 545583 7:92445452-99686985
2 BTRC , DPCD , FBXW4 , LBX1 , POLL , TLX1 , TLX1NB duplication Pathogenic 590885 10:102887490-103524625
3 duplication Pathogenic 590886
4 DLX5 NM_005221.6(DLX5):c.558G>T (p.Gln186His)SNV Pathogenic 91861 rs398122527 7:96650360-96650360 7:97021048-97021048
5 DLX5 NM_005221.6(DLX5):c.115G>T (p.Glu39Ter)SNV Pathogenic 156469 rs587777842 7:96653821-96653821 7:97024509-97024509
6 MAP3K20 NM_016653.3(MAP3K20):c.1103T>G (p.Phe368Cys)SNV Pathogenic 218144 rs863225437 2:174097087-174097087 2:173232359-173232359
7 PLAA NM_001031689.3(PLAA):c.1487-1G>ASNV Likely pathogenic 598964 rs1426488816 9:26913946-26913946 9:26913948-26913948
8 FGFR2 NM_000141.5(FGFR2):c.764G>A (p.Arg255Gln)SNV Likely pathogenic 869459 10:123279668-123279668 10:121520154-121520154
9 TP63 NM_003722.5(TP63):c.*235_*238deldeletion Uncertain significance 344394 rs886058225 3:189612523-189612526 3:189894734-189894737
10 TP63 NM_003722.5(TP63):c.*519C>TSNV Uncertain significance 344400 rs886058228 3:189612810-189612810 3:189895021-189895021
11 TP63 NM_003722.5(TP63):c.*1130_*1133deldeletion Uncertain significance 344407 rs886058229 3:189613419-189613422 3:189895630-189895633
12 TP63 NM_003722.5(TP63):c.*2555dupduplication Uncertain significance 344435 rs772929136 3:189614841-189614842 3:189897052-189897053
13 FBXW4 NM_022039.4(FBXW4):c.374T>C (p.Val125Ala)SNV Uncertain significance 298545 rs886046646 10:103454489-103454489 10:101694732-101694732
14 FBXW4 NM_022039.4(FBXW4):c.504_506GGC[3] (p.Ala170dup)short repeat Uncertain significance 298539 rs768227529 10:103454353-103454354 10:101694596-101694597
15 FBXW4 NM_022039.4(FBXW4):c.*311_*314dupduplication Uncertain significance 298524 rs562226127 10:103370733-103370734 10:101610976-101610977
16 TP63 NM_003722.5(TP63):c.*1947dupduplication Uncertain significance 344418 rs140654135 3:189614229-189614230 3:189896440-189896441
17 FBXW4 NM_022039.4(FBXW4):c.485_487AGG[6] (p.Glu168del)short repeat Likely benign 298540 rs560966094 10:103454358-103454360 10:101694601-101694603
18 TP63 NM_003722.5(TP63):c.*2636deldeletion Likely benign 344437 rs5855278 3:189614927-189614927 3:189897138-189897138
19 TP63 NM_003722.5(TP63):c.*2719_*2720deldeletion Likely benign 344438 rs574327104 3:189615007-189615008 3:189897218-189897219
20 TP63 NM_003722.5(TP63):c.*1844dupduplication Benign 344416 rs146332971 3:189614134-189614135 3:189896345-189896346
21 TP63 NM_003722.4(TP63):c.*2789A>GSNV Benign 369418 rs11708746 3:189615080-189615080 3:189897291-189897291
22 TP63 NM_003722.5(TP63):c.*2544deldeletion Benign 344434 rs201395656 3:189614829-189614829 3:189897040-189897040

Expression for Split-Hand/foot Malformation 1

Search GEO for disease gene expression data for Split-Hand/foot Malformation 1.

Pathways for Split-Hand/foot Malformation 1

GO Terms for Split-Hand/foot Malformation 1

Biological processes related to Split-Hand/foot Malformation 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 epithelial cell differentiation GO:0030855 9.26 TP63 DLX5
2 embryonic limb morphogenesis GO:0030326 9.16 TP63 DLX5
3 regulation of transcription, DNA-templated GO:0006355 9.1 ZNF138 ZNF133 ZNF132 ZNF131 TP63 DLX5
4 anatomical structure formation involved in morphogenesis GO:0048646 8.96 TP63 DLX5

Molecular functions related to Split-Hand/foot Malformation 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sequence-specific DNA binding GO:0043565 9.46 ZNF133 ZNF131 TP63 DLX5
2 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.43 ZNF131 TP63 DLX5
3 DNA binding GO:0003677 9.43 ZNF138 ZNF133 ZNF132 ZNF131 TP63 DLX5
4 DNA-binding transcription factor activity GO:0003700 9.1 ZNF138 ZNF133 ZNF132 ZNF131 TP63 DLX5

Sources for Split-Hand/foot Malformation 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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