SHFM1
MCID: SPL067
MIFTS: 47

Split-Hand/foot Malformation 1 (SHFM1)

Categories: Bone diseases, Ear diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases
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Aliases & Classifications for Split-Hand/foot Malformation 1

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

Name: Split-Hand/foot Malformation 1 57 38
Ectrodactyly 57 75 28 53 5 71
Split Hand-Foot Malformation 1 11 28 5 14
Split-Hand Deformity 57 75
Shfm1 57 11
Shfd1 57 11
Split-Hand/foot Malformation 1 with or Without Deafness 57
Split Hand/foot Malformation Type 1 12
Split-Hand/foot Malformation 71
Split-Hand/foot Deformity 1 57
Split Hand Foot Deformity 1 71
Ecd 57

Characteristics:


Inheritance:

Autosomal dominant 57

OMIM®:

57 (Updated 08-Dec-2022)
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


HPO:

30
split-hand/foot malformation 1:
Onset and clinical course variable expressivity


Classifications:



External Ids:

Disease Ontology 11 DOID:0090021
OMIM® 57 183600
OMIM Phenotypic Series 57 PS183600
ICD10 31 Q71.6
MedGen 40 C2931019
UMLS 71 C0265554 C2699510 C2931019

Summaries for Split-Hand/foot Malformation 1

OMIM®: 57 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) (Updated 08-Dec-2022)

MalaCards based summary: Split-Hand/foot Malformation 1, also known as ectrodactyly, is related to ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1 and split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive. An important gene associated with Split-Hand/foot Malformation 1 is DLX5 (Distal-Less Homeobox 5), and among its related pathways/superpathways are Head and neck squamous cell carcinoma and Validated transcriptional targets of deltaNp63 isoforms. Affiliated tissues include bone, heart and skin, and related phenotypes are split hand and split foot

Disease Ontology: 11 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: 75 Ectrodactyly, split hand, or cleft hand (derived from 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 499)
# Related Disease Score Top Affiliating Genes
1 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1 32.4 TP63 DLX5
2 split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive 32.3 TP63 SEM1 MAP3K20 DLX5
3 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 32.2 TP63 DLX5
4 split-hand/foot malformation 3 31.1 TP63 SEM1 DLX5
5 split-hand/foot malformation 4 31.1 TP63 SEM1 DLX5
6 ankyloblepharon-ectodermal defects-cleft lip/palate 30.9 TP63 FGFR2 DLX5
7 cleft palate, isolated 30.0 TP63 FGFR2 DLX5
8 isolated split hand-split foot malformation 30.0 TP63 SEM1 DLX5
9 rapp-hodgkin syndrome 29.7 TP63 DLX5
10 tooth agenesis 29.7 TP63 FGFR2 DLX5
11 split hand-foot malformation 29.3 ZNF138 TP63 SEM1 DLX5
12 chromosome 2q35 duplication syndrome 29.2 TP63 SEM1 FGFR2 DLX5
13 orofacial cleft 29.1 TP63 FGFR2 DLX5
14 ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome 11.6
15 hartsfield syndrome 11.6
16 erdheim-chester disease 11.6
17 brachydactyly-ectrodactyly with fibular aplasia or hypoplasia 11.5
18 intellectual disability-spasticity-ectrodactyly syndrome 11.5
19 microphthalmia, syndromic 8 11.5
20 ectrodactyly-polydactyly 11.5
21 phocomelia ectrodactyly deafness sinus arrhythmia 11.5
22 femur, unilateral bifid, with monodactylous ectrodactyly 11.4
23 adult syndrome 11.4
24 atrioventricular septal defect 11.4
25 anonychia-onychodystrophy with brachydactyly type b and ectrodactyly 11.3
26 acrofacial dysostosis 1, nager type 11.3
27 ectrodactyly and ectodermal dysplasia without cleft lip/palate 11.3
28 triphalangeal thumbs with brachyectrodactyly 11.3
29 tibial aplasia-ectrodactyly syndrome 11.3
30 aplasia cutis congenita, nonsyndromic 11.3
31 split-foot deformity with mandibulofacial dysostosis 11.3
32 cleft palate, cardiac defect, genital anomalies, and ectrodactyly 11.2
33 limb-mammary syndrome 11.2
34 anonychia-ectrodactyly 11.1
35 ectrodactyly cardiopathy dysmorphism 11.1
36 ectrodactyly-cleft palate syndrome 11.0
37 focal dermal hypoplasia 11.0
38 kasznica carlson coppedge syndrome 11.0
39 split-hand with congenital nystagmus, fundal changes, and cataracts 11.0
40 alopecia-contractures-dwarfism-intellectual disability syndrome 11.0
41 charlie m syndrome 11.0
42 cerebral primitive neuroectodermal tumor 11.0
43 complete atrioventricular canal 10.9
44 cystic medial necrosis of aorta 10.9
45 partial atrioventricular canal 10.9
46 split-hand/foot malformation 6 10.9
47 split-hand/foot malformation 2 10.9
48 split-hand/foot malformation 5 10.9
49 limb defects, distal transverse, with mental retardation and spasticity 10.9
50 ectrodactyly of lower limbs, congenital heart defect, and micrognathia 10.9

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:

30 (show all 21)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 split hand 30 Hallmark (90%) HP:0001171
2 split foot 30 Hallmark (90%) HP:0001839
3 cleft palate 30 Frequent (33%) HP:0000175
4 hand oligodactyly 30 Frequent (33%) HP:0001180
5 foot oligodactyly 30 Frequent (33%) HP:0001849
6 syndactyly 30 Frequent (33%) HP:0001159
7 intellectual disability 30 Very rare (1%) HP:0001249
8 hearing impairment 30 Very rare (1%) HP:0000365
9 abnormality of cardiovascular system morphology 30 Very rare (1%) HP:0030680
10 abnormal pinna morphology 30 Very rare (1%) HP:0000377
11 sensorineural hearing impairment 30 HP:0000407
12 abnormality of the genital system 30 HP:0000078
13 abnormality of the urinary system 30 HP:0000079
14 cutaneous finger syndactyly 30 HP:0010554
15 triphalangeal thumb 30 HP:0001199
16 median cleft lip 30 HP:0000161
17 ectrodactyly 30 HP:0100257
18 lacrimal duct aplasia 30 HP:0007925
19 2-3 toe syndactyly 30 HP:0004691
20 clinodactyly 30 HP:0030084
21 broad hallux 30 HP:0010055

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
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 (Updated 08-Dec-2022)

Drugs & Therapeutics for Split-Hand/foot Malformation 1

Search Clinical Trials, 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 Ectrodactyly 28
2 Split Hand-Foot Malformation 1 28 DLX5

Anatomical Context for Split-Hand/foot Malformation 1

Organs/tissues related to Split-Hand/foot Malformation 1:

MalaCards : Bone, Heart, Skin, Tongue, Breast, Pituitary, Eye

Publications for Split-Hand/foot Malformation 1

Articles related to Split-Hand/foot Malformation 1:

(show top 50) (show all 809)
# 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. 62 57 5
25196357 2014
2
Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation. 62 57 5
24496061 2014
3
Absent expression of the osteoblast-specific maternally imprinted genes, DLX5 and DLX6, causes split hand/split foot malformation type I. 62 57
25332435 2014
4
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. 62 57
23169702 2012
5
Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation. 62 57
22121204 2012
6
Characterization of the complex 7q21.3 rearrangement in a patient with bilateral split-foot malformation and hearing loss. 62 57
19449426 2009
7
Complex rearrangement of chromosomes 7q21.13-q22.1 confirms the ectrodactyly-deafness locus and suggests new candidate genes. 62 57
18080328 2008
8
Genotype-phenotype correlations in mapped split hand foot malformation (SHFM) patients. 62 57
16688749 2006
9
Refinement of the deletion in 7q21.3 associated with split hand/foot malformation type 1 and Mondini dysplasia. 62 57
15121782 2004
10
Pathogenesis of split-hand/split-foot malformation. 62 57
12668597 2003
11
Mouse model of split hand/foot malformation type I. 62 57
12112878 2002
12
Split hand/split foot malformation with hearing loss: first report of families linked to the SHFM1 locus in 7q21. 62 57
11168022 2001
13
Split hand/split foot malformation, deafness, and mental retardation with a complex cytogenetic rearrangement involving 7q21.3. 62 57
8782053 1996
14
Mapping the mouse dactylaplasia mutation, Dac, and a gene that controls its expression, mdac. 62 57
8666395 1995
15
Ectrodactyly and proximal/intermediate interstitial deletion 7q. 62 57
7747769 1995
16
Split foot and developmental retardation associated with a deletion of three microsatellite markers in 7q21.2-q22.1. 62 57
7606850 1995
17
Physical mapping of the split hand/split foot locus on chromosome 7 and implication in syndromic ectrodactyly. 62 57
7987313 1994
18
Evidence for locus heterogeneity in human autosomal dominant split hand/split foot malformation. 62 57
7912888 1994
19
Fine mapping of the autosomal dominant split hand/split foot locus on chromosome 7, band q21.3-q22.1. 62 57
8023840 1994
20
Inverted insertion of chromosome 7q and ectrodactyly. 62 57
8322806 1993
21
Ectrodactyly of hands and feet in a child with a complex translocation including 7q21.2. 62 57
1877619 1991
22
Ectro-amelia syndrome associated with an interstitial deletion of 7q. 62 57
2301476 1990
23
Interstitial long-arm deletion of chromosome 7 and ectrodactyly. 62 57
2929660 1989
24
The split-hand and split-foot anomaly in a central African Negro population. 62 57
6507501 1984
25
Monodactylous splithand-splitfoot. A malformation occurring in three distinct genetic types. 62 57
7389732 1980
26
A problem for genetic counselling - split hand deformity. 62 57
891014 1977
27
Dominant ectrodactyly and possible germinal mosaicism. 62 57
5079103 1972
28
A recessive form of ectrodactyly, and its implications in genetic counseling. 62 57
5094721 1971
29
Ectrodactyly--evidence in favour of a disturbed segregation in the offspring of affected males. 62 57
13834546 1960
30
Two pedigrees of ectrodactyly. 62 57
24541402 1951
31
Discrepancies in upper and lower limb patterning in split hand foot malformation. 57
16207208 2005
32
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. 57
11424924 2001
33
Further evidence for germinal mosaicism in cleft hand/cleft foot syndrome. Two affected halfsisters and normal father. 57
11693788 2001
34
Defect in the maintenance of the apical ectodermal ridge in the Dactylaplasia mouse. 57
9733575 1998
35
Bilateral split hand/foot malformation and inv(7)(p22q21.3). 57
7616545 1995
36
Non-Mendelian transmission in a human developmental disorder: split hand/split foot. 57
7942849 1994
37
On the inheritance of the split hand/split foot malformation. 57
7802032 1994
38
The genetics of human limb development. 57
7912883 1994
39
Split hand/split foot anomaly in a family segregating a balanced translocation with breakpoint on 7q22.1. 57
8279479 1993
40
Human situs determination and chromosome constitution 46,XY,ins(7;8)(q22;q12q24) 57
8192752 1993
41
Bilateral split hand and split foot malformation in a boy with a de novo interstitial deletion of 7q21.3. 57
1895319 1991
42
Why is Mendelian segregation so exact? 57
1909864 1991
43
[Interstitial deletion of the long arm of chromosome 7 and its clinical correlations]. 57
6680429 1983
44
Another case of split-foot mutation in two sibs. 57
4320415 1970
45
[Split hand and foot with familial occurrence]. 57
14479171 1962
46
[Delayed mutation in man; a critical observation on the work of Ch. Auerbachs (1956)]. 57
13509525 1958
47
A possible case of delayed mutation in man. 57
13314396 1956
48
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. 53 62
19903181 2010
49
A 19-year follow-up of a patient with type 3 ectrodactyly-ectodermal dysplasia-clefting syndrome who developed non-Hodgkin lymphoma. 53 62
19716498 2009
50
A new mutation in TP63 is associated with age-related pathology. 53 62
17609671 2007

Variations for Split-Hand/foot Malformation 1

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

5 (show all 17)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 overlap with 67 genes GRCh37/hg19 7q21.2-22.1(chr7:92445452-99686985)x1 CN LOSS Pathogenic
545583 GRCh37: 7:92445452-99686985
GRCh38:
2 DLX5 NM_005221.6(DLX5):c.115G>T (p.Glu39Ter) SNV Pathogenic
156469 rs587777842 GRCh37: 7:96653821-96653821
GRCh38: 7:97024509-97024509
3 MAP3K20-AS1, MAP3K20 NM_016653.3(MAP3K20):c.1103T>G (p.Phe368Cys) SNV Pathogenic
218144 rs863225437 GRCh37: 2:174097087-174097087
GRCh38: 2:173232359-173232359
4 DLX5 NM_005221.6(DLX5):c.558G>T (p.Gln186His) SNV Pathogenic
91861 rs398122527 GRCh37: 7:96650360-96650360
GRCh38: 7:97021048-97021048
5 PLAA NM_001031689.3(PLAA):c.1487-1G>A SNV Likely Pathogenic
598964 rs1426488816 GRCh37: 9:26913946-26913946
GRCh38: 9:26913948-26913948
6 FGFR2 NM_000141.5(FGFR2):c.764G>A (p.Arg255Gln) SNV Likely Pathogenic
869459 rs1850314485 GRCh37: 10:123279668-123279668
GRCh38: 10:121520154-121520154
7 TP63 NM_003722.5(TP63):c.*519C>T SNV Uncertain Significance
344400 rs886058228 GRCh37: 3:189612810-189612810
GRCh38: 3:189895021-189895021
8 TP63 NM_003722.5(TP63):c.*1947dup DUP Uncertain Significance
344418 rs140654135 GRCh37: 3:189614229-189614230
GRCh38: 3:189896440-189896441
9 TP63 NM_003722.5(TP63):c.*2555dup DUP Uncertain Significance
344435 rs772929136 GRCh37: 3:189614841-189614842
GRCh38: 3:189897052-189897053
10 TP63 NM_003722.5(TP63):c.*1130_*1133del DEL Uncertain Significance
344407 rs886058229 GRCh37: 3:189613419-189613422
GRCh38: 3:189895630-189895633
11 TP63 NM_003722.5(TP63):c.*235_*238del DEL Uncertain Significance
344394 rs886058225 GRCh37: 3:189612523-189612526
GRCh38: 3:189894734-189894737
12 UBA2 NM_005499.3(UBA2):c.364C>G (p.Arg122Gly) SNV Uncertain Significance
978773 rs1599889628 GRCh37: 19:34925778-34925778
GRCh38: 19:34434873-34434873
13 TP63 NM_003722.5(TP63):c.*2719_*2720del DEL Likely Benign
344438 rs574327104 GRCh37: 3:189615007-189615008
GRCh38: 3:189897218-189897219
14 TP63 NM_003722.5(TP63):c.*2636del DEL Likely Benign
344437 rs5855278 GRCh37: 3:189614927-189614927
GRCh38: 3:189897138-189897138
15 TP63 NM_003722.5(TP63):c.*2544del DEL Benign
344434 rs201395656 GRCh37: 3:189614829-189614829
GRCh38: 3:189897040-189897040
16 TP63 NM_003722.5(TP63):c.*1844dup DUP Benign
344416 rs146332971 GRCh37: 3:189614134-189614135
GRCh38: 3:189896345-189896346
17 TP63 NM_003722.4(TP63):c.*2789A>G SNV Benign
369418 rs11708746 GRCh37: 3:189615080-189615080
GRCh38: 3:189897291-189897291

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

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

# Super pathways Score Top Affiliating Genes
1 10.82 TP63 FGFR2
2 10.3 TP63 DLX5

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 hair follicle morphogenesis GO:0031069 9.62 TP63 FGFR2
2 embryonic limb morphogenesis GO:0030326 9.54 TP63 DLX5
3 bone morphogenesis GO:0060349 9.43 FGFR2 DLX5
4 epithelial cell differentiation GO:0030855 9.35 TP63 FGFR2 DLX5
5 anatomical structure formation involved in morphogenesis GO:0048646 9.33 TP63 DLX5
6 squamous basal epithelial stem cell differentiation involved in prostate gland acinus development GO:0060529 8.92 TP63 FGFR2

Sources for Split-Hand/foot Malformation 1

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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