MCID: SPL067
MIFTS: 38

Split-Hand/foot Malformation 1

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

Aliases & Classifications for Split-Hand/foot Malformation 1

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

Name: Split-Hand/foot Malformation 1 57 29 6
Ectrodactyly 57 76 55 6 73
Shfm1 57 12 53
Shfd1 57 12 53
Split Hand-Foot Malformation 1 12 15
Split Hand Foot Deformity 1 53 73
Split-Hand Deformity 57 76
Split-Hand/foot Malformation 1 with or Without Deafness 57
Split-Hand/foot Deformity 1; Shfd1; Shsf1 57
Split Hand/foot Malformation Type 1 13
Split Hand/foot Malformation 1 57
Split Hand Foot Malformation 1 53
Split-Hand/foot Malformation 73
Split-Hand/foot Deformity 1 57
Split Hand Malformation1 53
Split Hand Deformity 1 53
Ectrodactyly; Ecd 57
Ecd 57

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

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
one family reported with mutation in a heterozygous mutation in dlx5 (last curated october 2014)


HPO:

32
split-hand/foot malformation 1:
Onset and clinical course variable expressivity incomplete penetrance
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Split-Hand/foot Malformation 1

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 1, also known as ectrodactyly, is related to split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive and isolated split hand-split foot malformation. An important gene associated with Split-Hand/foot Malformation 1 is SEM1 (SEM1, 26S Proteasome Complex Subunit). Affiliated tissues include bone, and related phenotypes are clinodactyly and intellectual disability

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.

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)

Wikipedia : 76 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 78)
# Related Disease Score Top Affiliating Genes
1 split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive 33.7 DLX5 SEM1
2 isolated split hand-split foot malformation 31.8 DLX5 SEM1 TP63
3 split hand-foot malformation 29.2 DLX5 MAP3K20 SEM1 TP63
4 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1 12.4
5 ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome 12.3
6 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 12.2
7 femur bifid with monodactylous ectrodactyly 12.1
8 intellectual disability-spasticity-ectrodactyly syndrome 12.1
9 fibular aplasia ectrodactyly 12.1
10 ectrodactyly and ectodermal dysplasia without cleft lip/palate 12.0
11 brachydactyly-ectrodactyly with fibular aplasia or hypoplasia 12.0
12 femur, unilateral bifid, with monodactylous ectrodactyly 12.0
13 anonychia-onychodystrophy with brachydactyly type b and ectrodactyly 12.0
14 cleft palate, cardiac defect, genital anomalies, and ectrodactyly 12.0
15 ectrodactyly cardiopathy dysmorphism 12.0
16 ectrodactyly-cleft palate syndrome 11.9
17 hartsfield syndrome 11.9
18 ectrodactyly-polydactyly 11.9
19 anonychia-ectrodactyly 11.8
20 phocomelia-ectrodactyly, ear malformation, deafness, and sinus arrhythmia 11.8
21 phocomelia ectrodactyly deafness sinus arrhythmia 11.8
22 tibial aplasia-ectrodactyly syndrome 11.8
23 ectrodactyly of lower limbs, congenital heart defect, and micrognathia 11.7
24 cleft palate cardiac defect ectrodactyly 11.7
25 holoprosencephaly ectrodactyly cleft lip palate 11.7
26 hydrops ectrodactyly syndactyly 11.7
27 short stature monodactylous ectrodactyly cleft palate 11.7
28 tibial aplasia ectrodactyly hydrocephalus 11.7
29 adult syndrome 11.7
30 atrioventricular septal defect 11.7
31 limb-mammary syndrome 11.6
32 microphthalmia, syndromic 8 11.6
33 split-hand/foot malformation with long bone deficiency 1 11.5
34 triphalangeal thumbs with brachyectrodactyly 11.5
35 split-foot deformity with mandibulofacial dysostosis 11.5
36 acrofacial dysostosis 1, nager type 11.3
37 erdheim-chester disease 11.3
38 hemifacial atrophy, progressive 10.9
39 cerebritis 10.1
40 lipogranulomatosis 10.0
41 breast cancer 9.9
42 paranoid personality disorder 9.9 DLX5 SEM1
43 parametritis 9.8
44 hemiplegic migraine 9.8
45 split-hand/foot malformation 6 9.7 DLX5 SEM1 TP63
46 split-hand/foot malformation 5 9.7 DLX5 SEM1 TP63
47 creutzfeldt-jakob disease 9.7
48 multiple system atrophy 1 9.7
49 alexander disease 9.7
50 neurodegeneration with brain iron accumulation 1 9.7

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

Symptoms via clinical synopsis from OMIM:

57
Skeletal Feet:
clinodactyly
ectrodactyly
split foot
broad hallux

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


Clinical features from OMIM:

183600

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

32 (show all 21)
# Description HPO Frequency HPO Source Accession
1 clinodactyly 32 HP:0030084
2 intellectual disability 32 very rare (1%) HP:0001249
3 hearing impairment 32 very rare (1%) HP:0000365
4 sensorineural hearing impairment 32 HP:0000407
5 cleft palate 32 frequent (33%) HP:0000175
6 abnormality of the pinna 32 very rare (1%) HP:0000377
7 split hand 32 hallmark (90%) HP:0001171
8 abnormality of the genital system 32 HP:0000078
9 cutaneous finger syndactyly 32 HP:0010554
10 triphalangeal thumb 32 HP:0001199
11 abnormality of the urinary system 32 HP:0000079
12 abnormality of cardiovascular system morphology 32 very rare (1%) HP:0030680
13 median cleft lip 32 HP:0000161
14 ectrodactyly 32 HP:0100257
15 2-3 toe syndactyly 32 HP:0004691
16 syndactyly 32 frequent (33%) HP:0001159
17 split foot 32 hallmark (90%) HP:0001839
18 foot oligodactyly 32 frequent (33%) HP:0001849
19 broad hallux 32 HP:0010055
20 lacrimal duct aplasia 32 HP:0007925
21 hand oligodactyly 32 frequent (33%) HP:0001180

Drugs & Therapeutics for Split-Hand/foot Malformation 1

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 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

Anatomical Context for Split-Hand/foot Malformation 1

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

41
Bone

Publications for Split-Hand/foot Malformation 1

Articles related to Split-Hand/foot Malformation 1:

# Title Authors Year
1
Phenotypic subregions within the split-hand/foot malformation 1 locus. ( 26839112 )
2016

Variations for Split-Hand/foot Malformation 1

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

6
(show top 50) (show all 138)
# Gene Variation Type Significance SNP ID Assembly Location
1 DLX5 NM_005221.5(DLX5): c.558G> T (p.Gln186His) single nucleotide variant Pathogenic rs398122527 GRCh37 Chromosome 7, 96650360: 96650360
2 DLX5 NM_005221.5(DLX5): c.558G> T (p.Gln186His) single nucleotide variant Pathogenic rs398122527 GRCh38 Chromosome 7, 97021048: 97021048
3 DLX5 NM_005221.5(DLX5): c.115G> T (p.Glu39Ter) single nucleotide variant Pathogenic rs587777842 GRCh37 Chromosome 7, 96653821: 96653821
4 DLX5 NM_005221.5(DLX5): c.115G> T (p.Glu39Ter) single nucleotide variant Pathogenic rs587777842 GRCh38 Chromosome 7, 97024509: 97024509
5 MAP3K20 NM_016653.2(MAP3K20): c.1103T> G (p.Phe368Cys) single nucleotide variant Pathogenic rs863225437 GRCh37 Chromosome 2, 174097087: 174097087
6 MAP3K20 NM_016653.2(MAP3K20): c.1103T> G (p.Phe368Cys) single nucleotide variant Pathogenic rs863225437 GRCh38 Chromosome 2, 173232359: 173232359
7 TP63 NM_003722.4(TP63): c.859C> T (p.Leu287=) single nucleotide variant Benign/Likely benign rs33979049 GRCh37 Chromosome 3, 189584563: 189584563
8 TP63 NM_003722.4(TP63): c.859C> T (p.Leu287=) single nucleotide variant Benign/Likely benign rs33979049 GRCh38 Chromosome 3, 189866774: 189866774
9 TP63 NM_003722.4(TP63): c.1587C> T (p.Leu529=) single nucleotide variant Likely benign rs141847552 GRCh38 Chromosome 3, 189889419: 189889419
10 TP63 NM_003722.4(TP63): c.1587C> T (p.Leu529=) single nucleotide variant Likely benign rs141847552 GRCh37 Chromosome 3, 189607208: 189607208
11 TP63 NM_003722.4(TP63): c.*45C> T single nucleotide variant Benign rs34057105 GRCh38 Chromosome 3, 189894547: 189894547
12 TP63 NM_003722.4(TP63): c.*45C> T single nucleotide variant Benign rs34057105 GRCh37 Chromosome 3, 189612336: 189612336
13 TP63 NM_003722.4(TP63): c.1531C> A (p.Pro511Thr) single nucleotide variant Likely benign rs148076109 GRCh37 Chromosome 3, 189607152: 189607152
14 TP63 NM_003722.4(TP63): c.1531C> A (p.Pro511Thr) single nucleotide variant Likely benign rs148076109 GRCh38 Chromosome 3, 189889363: 189889363
15 TP63 NM_003722.4(TP63): c.303G> A (p.Ser101=) single nucleotide variant Likely benign rs186864205 GRCh37 Chromosome 3, 189456542: 189456542
16 TP63 NM_003722.4(TP63): c.303G> A (p.Ser101=) single nucleotide variant Likely benign rs186864205 GRCh38 Chromosome 3, 189738753: 189738753
17 TP63 NM_003722.4(TP63): c.699A> G (p.Lys233=) single nucleotide variant Likely benign rs199727371 GRCh37 Chromosome 3, 189582140: 189582140
18 TP63 NM_003722.4(TP63): c.699A> G (p.Lys233=) single nucleotide variant Likely benign rs199727371 GRCh38 Chromosome 3, 189864351: 189864351
19 TP63 NM_003722.4(TP63): c.766+3A> G single nucleotide variant Uncertain significance rs886058221 GRCh37 Chromosome 3, 189582210: 189582210
20 TP63 NM_003722.4(TP63): c.766+3A> G single nucleotide variant Uncertain significance rs886058221 GRCh38 Chromosome 3, 189864421: 189864421
21 TP63 NM_003722.4(TP63): c.1652+14A> C single nucleotide variant Likely benign rs150685395 GRCh38 Chromosome 3, 189889498: 189889498
22 TP63 NM_003722.4(TP63): c.1652+14A> C single nucleotide variant Likely benign rs150685395 GRCh37 Chromosome 3, 189607287: 189607287
23 TP63 NM_003722.4(TP63): c.*235_*238delGTAG deletion Uncertain significance rs886058225 GRCh38 Chromosome 3, 189894737: 189894740
24 TP63 NM_003722.4(TP63): c.*235_*238delGTAG deletion Uncertain significance rs886058225 GRCh37 Chromosome 3, 189612526: 189612529
25 TP63 NM_003722.4(TP63): c.*627T> C single nucleotide variant Likely benign rs184452906 GRCh38 Chromosome 3, 189895129: 189895129
26 TP63 NM_003722.4(TP63): c.*627T> C single nucleotide variant Likely benign rs184452906 GRCh37 Chromosome 3, 189612918: 189612918
27 TP63 NM_003722.4(TP63): c.*2123C> T single nucleotide variant Likely benign rs36064124 GRCh38 Chromosome 3, 189896625: 189896625
28 TP63 NM_003722.4(TP63): c.*2123C> T single nucleotide variant Likely benign rs36064124 GRCh37 Chromosome 3, 189614414: 189614414
29 TP63 NM_003722.4(TP63): c.*2197C> A single nucleotide variant Uncertain significance rs886058237 GRCh37 Chromosome 3, 189614488: 189614488
30 TP63 NM_003722.4(TP63): c.*2197C> A single nucleotide variant Uncertain significance rs886058237 GRCh38 Chromosome 3, 189896699: 189896699
31 TP63 NM_003722.4(TP63): c.*2625A> T single nucleotide variant Likely benign rs35694511 GRCh38 Chromosome 3, 189897127: 189897127
32 TP63 NM_003722.4(TP63): c.*2625A> T single nucleotide variant Likely benign rs35694511 GRCh37 Chromosome 3, 189614916: 189614916
33 TP63 NM_003722.4(TP63): c.*2719_*2720delTT deletion Likely benign rs886058242 GRCh38 Chromosome 3, 189897221: 189897222
34 TP63 NM_003722.4(TP63): c.*2719_*2720delTT deletion Likely benign rs886058242 GRCh37 Chromosome 3, 189615010: 189615011
35 TP63 NM_003722.4(TP63): c.409G> C (p.Asp137His) single nucleotide variant Uncertain significance rs762935508 GRCh37 Chromosome 3, 189526145: 189526145
36 TP63 NM_003722.4(TP63): c.409G> C (p.Asp137His) single nucleotide variant Uncertain significance rs762935508 GRCh38 Chromosome 3, 189808356: 189808356
37 TP63 NM_003722.4(TP63): c.766+5G> A single nucleotide variant Uncertain significance rs374425727 GRCh37 Chromosome 3, 189582212: 189582212
38 TP63 NM_003722.4(TP63): c.766+5G> A single nucleotide variant Uncertain significance rs374425727 GRCh38 Chromosome 3, 189864423: 189864423
39 TP63 NM_003722.4(TP63): c.1374A> G (p.Ser458=) single nucleotide variant Uncertain significance rs141794685 GRCh38 Chromosome 3, 189886418: 189886418
40 TP63 NM_003722.4(TP63): c.1374A> G (p.Ser458=) single nucleotide variant Uncertain significance rs141794685 GRCh37 Chromosome 3, 189604207: 189604207
41 TP63 NM_003722.4(TP63): c.*232T> C single nucleotide variant Likely benign rs569527175 GRCh38 Chromosome 3, 189894734: 189894734
42 TP63 NM_003722.4(TP63): c.*232T> C single nucleotide variant Likely benign rs569527175 GRCh37 Chromosome 3, 189612523: 189612523
43 TP63 NM_003722.4(TP63): c.*379T> A single nucleotide variant Likely benign rs192879052 GRCh38 Chromosome 3, 189894881: 189894881
44 TP63 NM_003722.4(TP63): c.*379T> A single nucleotide variant Likely benign rs192879052 GRCh37 Chromosome 3, 189612670: 189612670
45 TP63 NM_003722.4(TP63): c.*519C> T single nucleotide variant Uncertain significance rs886058228 GRCh38 Chromosome 3, 189895021: 189895021
46 TP63 NM_003722.4(TP63): c.*519C> T single nucleotide variant Uncertain significance rs886058228 GRCh37 Chromosome 3, 189612810: 189612810
47 TP63 NM_003722.4(TP63): c.*638C> G single nucleotide variant Benign rs6444406 GRCh38 Chromosome 3, 189895140: 189895140
48 TP63 NM_003722.4(TP63): c.*638C> G single nucleotide variant Benign rs6444406 GRCh37 Chromosome 3, 189612929: 189612929
49 TP63 NM_003722.4(TP63): c.*854A> G single nucleotide variant Likely benign rs187751631 GRCh37 Chromosome 3, 189613145: 189613145
50 TP63 NM_003722.4(TP63): c.*854A> G single nucleotide variant Likely benign rs187751631 GRCh38 Chromosome 3, 189895356: 189895356

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

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

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 9.17 DLX5 MAP3K20 TP63 ZNF133 ZNF143 ZNF148

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

# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 9.73 DLX5 TP63 ZNF133 ZNF143 ZNF148 ZNF44
2 positive regulation of transcription by RNA polymerase II GO:0045944 9.71 DLX5 TP63 ZNF143 ZNF148
3 cell proliferation GO:0008283 9.54 DLX5 MAP3K20 TP63
4 transcription by RNA polymerase II GO:0006366 9.46 DLX5 TP63 ZNF143 ZNF148
5 epithelial cell differentiation GO:0030855 9.43 DLX5 TP63
6 embryonic limb morphogenesis GO:0030326 9.32 DLX5 TP63
7 transcription, DNA-templated GO:0006351 9.1 DLX5 TP63 ZNF133 ZNF143 ZNF148 ZNF44
8 anatomical structure formation involved in morphogenesis GO:0048646 8.96 DLX5 TP63

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

# Name GO ID Score Top Affiliating Genes
1 metal ion binding GO:0046872 9.85 MAP3K20 TP63 ZNF133 ZNF143 ZNF148 ZNF44
2 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.5 DLX5 ZNF143 ZNF148
3 sequence-specific DNA binding GO:0043565 9.46 DLX5 TP63 ZNF133 ZNF148
4 transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding GO:0001077 9.43 DLX5 TP63 ZNF143
5 DNA binding GO:0003677 9.43 DLX5 TP63 ZNF133 ZNF143 ZNF148 ZNF44
6 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000981 9.1 DLX5 TP63 ZNF133 ZNF143 ZNF148 ZNF44

Sources for Split-Hand/foot Malformation 1

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
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