SHFM6
MCID: SPL033
MIFTS: 37

Split-Hand/foot Malformation 6 (SHFM6)

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

Aliases & Classifications for Split-Hand/foot Malformation 6

MalaCards integrated aliases for Split-Hand/foot Malformation 6:

Name: Split-Hand/foot Malformation 6 57 72 29 13 6 70
Shfm6 57 12 72
Split Hand-Foot Malformation 6 12 15
Split-Hand/foot Malformation, Type 6 39
Ectrodactyly, Autosomal Recessive 57
Ectrodactyly Autosomal Recessive 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype


HPO:

31
split-hand/foot malformation 6:
Inheritance autosomal recessive inheritance
Onset and clinical course incomplete penetrance


Classifications:



External Ids:

Disease Ontology 12 DOID:0090026
OMIM® 57 225300
OMIM Phenotypic Series 57 PS183600
ICD9CM 34 755.58
SNOMED-CT 67 81208006
ICD10 32 Q71.6
MedGen 41 C2749665
UMLS 70 C0265554 C2749665

Summaries for Split-Hand/foot Malformation 6

OMIM® : 57 Split-hand/split-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 SHFM have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting (Elliott and Evans, 2006). For a general phenotypic description and a discussion of genetic heterogeneity of split-hand/foot malformations, see SHFM1 (183600). (225300) (Updated 20-May-2021)

MalaCards based summary : Split-Hand/foot Malformation 6, also known as shfm6, is related to split hand-foot malformation and split hand split foot malformation autosomal recessive. An important gene associated with Split-Hand/foot Malformation 6 is WNT10B (Wnt Family Member 10B), and among its related pathways/superpathways is MECP2 and Associated Rett Syndrome. Related phenotypes are split hand and finger syndactyly

Disease Ontology : 12 A split-hand/foot malformation that has material basis in homozygous mutation in the WNT10B gene on chromosome 12q13.

UniProtKB/Swiss-Prot : 72 Split-hand/foot malformation 6: 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 have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting.

Related Diseases for Split-Hand/foot Malformation 6

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

(show all 21)
# Related Disease Score Top Affiliating Genes
1 split hand-foot malformation 29.5 WNT10B TP63 SEM1 FBXW4 DPCD DLX6
2 split hand split foot malformation autosomal recessive 10.9
3 split hand/foot malformation x-linked 10.9
4 lacrimoauriculodentodigital syndrome 9.9 FBXW4 BHLHA9
5 agnathia-otocephaly complex 9.9 DLX6 DLX5
6 split-hand/foot malformation 1 9.8 TP63 SEM1 DLX5
7 tooth agenesis 9.7 WNT10B TP63 DLX5
8 orofacial cleft 9.7 TP63 DLX6 DLX5
9 orofacial cleft 8 9.7 TP63 DLX6 DLX5
10 rapp-hodgkin syndrome 9.7 TP63 DLX6 DLX5
11 orofacial cleft 4 9.6 WNT10B TP63 SEM1 DLX6
12 brachydactyly, type a2 9.6 LBX1 FBXW4 DPCD
13 cleft palate, isolated 9.4 TP63 DLX6 DLX5
14 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 9.3 WNT10B TP63 DLX6 DLX5 BHLHA9
15 split-hand/foot malformation 5 9.2 TP63 SEM1 FBXW4 DLX6 DLX5 BHLHA9
16 isolated split hand-split foot malformation 9.0 WNT10B TP63 SEM1 EPS15L1 DLX6 DLX5
17 split-hand/foot malformation 2 9.0 WNT10B TP63 SEM1 FBXW4 DLX6 DLX5
18 split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive 9.0 WNT10B TP63 SEM1 FBXW4 DLX6 DLX5
19 chromosome 2q35 duplication syndrome 9.0 WNT10B TP63 SEM1 FBXW4 DLX6 DLX5
20 split-hand/foot malformation 3 8.8 SEM1 LBX1 FBXW4 DPCD DLX6 DLX5
21 split-hand/foot malformation 4 8.0 WNT10B TP63 SEM1 LBX1 FBXW4 EPS15L1

Graphical network of the top 20 diseases related to Split-Hand/foot Malformation 6:



Diseases related to Split-Hand/foot Malformation 6

Symptoms & Phenotypes for Split-Hand/foot Malformation 6

Human phenotypes related to Split-Hand/foot Malformation 6:

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 split hand 31 HP:0001171
2 finger syndactyly 31 HP:0006101
3 toe syndactyly 31 HP:0001770
4 hand oligodactyly 31 HP:0001180
5 split foot 31 HP:0001839
6 foot oligodactyly 31 HP:0001849

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal Hands:
split hand
ectrodactyly

Skeletal Feet:
split foot

Skin Nails Hair Hair:
sparse hair
interrupted eyebrows

Clinical features from OMIM®:

225300 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Split-Hand/foot Malformation 6:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.8 DLX5 DLX6 EPS15L1 FBXW4 LBX1 TP63
2 limbs/digits/tail MP:0005371 9.8 BHLHA9 DLX5 DLX6 EPS15L1 FBXW4 LBX1
3 nervous system MP:0003631 9.7 BHLHA9 DLX5 DLX6 DPCD EPS15L1 LBX1
4 respiratory system MP:0005388 9.35 DLX5 DLX6 DPCD EPS15L1 TP63
5 skeleton MP:0005390 9.1 DLX5 DLX6 DPCD FBXW4 TP63 WNT10B

Drugs & Therapeutics for Split-Hand/foot Malformation 6

Search Clinical Trials , NIH Clinical Center for Split-Hand/foot Malformation 6

Genetic Tests for Split-Hand/foot Malformation 6

Genetic tests related to Split-Hand/foot Malformation 6:

# Genetic test Affiliating Genes
1 Split-Hand/foot Malformation 6 29 WNT10B

Anatomical Context for Split-Hand/foot Malformation 6

Publications for Split-Hand/foot Malformation 6

Articles related to Split-Hand/foot Malformation 6:

(show all 18)
# Title Authors PMID Year
1
Split hand-foot malformation and a novel WNT10B mutation. 6 57 61
29427788 2018
2
Homozygous nonsense mutation in WNT10B and sporadic split-hand/foot malformation (SHFM) with autosomal recessive inheritance. 57 6
20635353 2010
3
Homozygous WNT10b mutation and complex inheritance in Split-Hand/Foot Malformation. 57 6
18515319 2008
4
Evidence for autosomal recessive inheritance of split hand/split foot malformation: a report of nine cases. 57 6
12072797 2002
5
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 6
25741868 2015
6
Genotype-phenotype correlations in mapped split hand foot malformation (SHFM) patients. 57
16688749 2006
7
Is there an autosomal recessive form of the split hand and split foot malformation? 57
2918544 1989
8
Ectrodactyly in sisters and half sisters. 57
3346888 1988
9
Ectrodactyly in sisters and half sisters. 57
3585937 1987
10
Split-hand and split-foot deformity inherited as an autosomal recessive trait. 57
1248167 1976
11
A recessive form of ectrodactyly, and its implications in genetic counseling. 57
5094721 1971
12
A classification system for split-hand/ foot malformation (SHFM): A proposal based on 3 pedigrees with WNT10B mutations. 61
31421290 2020
13
WNT10B variants in split hand/foot malformation: Report of three novel families and review of the literature. 61
31050392 2019
14
Duplication of 10q24 locus: broadening the clinical and radiological spectrum. 61
30622331 2019
15
Bhlha9 regulates apical ectodermal ridge formation during limb development. 61
28324176 2018
16
Microduplications of 10q24 Detected in Two Chinese Patients with Split-hand/foot Malformation Type 3. 61
29263051 2017
17
Novel homozygous mutations in the WNT10B gene underlying autosomal recessive split hand/foot malformation in three consanguineous families. 61
24211389 2014
18
A novel homozygous missense mutation in WNT10B in familial split-hand/foot malformation. 61
21554266 2012

Variations for Split-Hand/foot Malformation 6

ClinVar genetic disease variations for Split-Hand/foot Malformation 6:

6 (show all 12)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 WNT10B NM_003394.4(WNT10B):c.817del (p.Ala273fs) Deletion Pathogenic 634645 GRCh37: 12:49360231-49360231
GRCh38: 12:48966448-48966448
2 WNT10B NM_003394.4(WNT10B):c.458_461dup (p.Asp155fs) Duplication Pathogenic 30237 rs763548858 GRCh37: 12:49361978-49361979
GRCh38: 12:48968195-48968196
3 WNT10B NM_003394.4(WNT10B):c.689_691ACA[2] (p.Asn232del) Microsatellite Pathogenic 599263 rs776938956 GRCh37: 12:49361743-49361745
GRCh38: 12:48967960-48967962
4 WNT10B NM_003394.4(WNT10B):c.994C>T (p.Arg332Trp) SNV Pathogenic 7630 rs121918349 GRCh37: 12:49360054-49360054
GRCh38: 12:48966271-48966271
5 WNT10B NM_003394.4(WNT10B):c.817dup (p.Ala273fs) Duplication Pathogenic 634647 GRCh37: 12:49360230-49360231
GRCh38: 12:48966447-48966448
6 WNT10B NM_003394.4(WNT10B):c.505C>T (p.Arg169Ter) SNV Pathogenic 1029700 GRCh37: 12:49361935-49361935
GRCh38: 12:48968152-48968152
7 WNT10B NM_003394.4(WNT10B):c.338-1G>C SNV Pathogenic/Likely pathogenic 545118 rs1163162816 GRCh37: 12:49362103-49362103
GRCh38: 12:48968320-48968320
8 WNT10B NM_003394.4(WNT10B):c.676C>T (p.Arg226Ter) SNV Likely pathogenic 522440 rs763991433 GRCh37: 12:49361764-49361764
GRCh38: 12:48967981-48967981
9 WNT10B NM_003394.4(WNT10B):c.746G>T (p.Cys249Phe) SNV Likely pathogenic 634646 GRCh37: 12:49360302-49360302
GRCh38: 12:48966519-48966519
10 WNT10B NM_003394.4(WNT10B):c.949T>A (p.Phe317Ile) SNV Likely pathogenic 634648 GRCh37: 12:49360099-49360099
GRCh38: 12:48966316-48966316
11 WNT10B NM_003394.4(WNT10B):c.257A>C (p.Gln86Pro) SNV Likely pathogenic 638164 rs1592252556 GRCh37: 12:49363952-49363952
GRCh38: 12:48970169-48970169
12 WNT10B NM_003394.4(WNT10B):c.290T>C (p.Leu97Pro) SNV Uncertain significance 623323 rs1458667581 GRCh37: 12:49363919-49363919
GRCh38: 12:48970136-48970136

UniProtKB/Swiss-Prot genetic disease variations for Split-Hand/foot Malformation 6:

72
# Symbol AA change Variation ID SNP ID
1 WNT10B p.Arg332Trp VAR_062516 rs121918349

Expression for Split-Hand/foot Malformation 6

Search GEO for disease gene expression data for Split-Hand/foot Malformation 6.

Pathways for Split-Hand/foot Malformation 6

Pathways related to Split-Hand/foot Malformation 6 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.42 DLX6 DLX5

GO Terms for Split-Hand/foot Malformation 6

Cellular components related to Split-Hand/foot Malformation 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin GO:0000785 9.02 TP63 LBX1 DLX6 DLX5 BHLHA9

Biological processes related to Split-Hand/foot Malformation 6 according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 cell differentiation GO:0030154 9.85 TP63 LBX1 DLX6 DLX5
2 regulation of transcription by RNA polymerase II GO:0006357 9.8 WNT10B TP63 LBX1 DLX6 DLX5 BHLHA9
3 positive regulation of canonical Wnt signaling pathway GO:0090263 9.63 WNT10B SEM1 DLX5
4 skeletal system development GO:0001501 9.58 TP63 DLX6 DLX5
5 positive regulation of osteoblast differentiation GO:0045669 9.54 WNT10B TP63
6 roof of mouth development GO:0060021 9.52 DLX6 DLX5
7 positive regulation of epithelial cell proliferation GO:0050679 9.51 DLX6 DLX5
8 multicellular organism development GO:0007275 9.5 WNT10B TP63 LBX1 FBXW4 DLX6 DLX5
9 inner ear morphogenesis GO:0042472 9.49 DLX6 DLX5
10 developmental process GO:0032502 9.48 TP63 BHLHA9
11 head development GO:0060322 9.43 DLX6 DLX5
12 epithelial cell differentiation GO:0030855 9.43 TP63 DLX6 DLX5
13 embryo development GO:0009790 9.37 DLX6 DLX5
14 anatomical structure formation involved in morphogenesis GO:0048646 9.33 TP63 DLX6 DLX5
15 embryonic limb morphogenesis GO:0030326 8.92 TP63 FBXW4 DLX6 DLX5

Molecular functions related to Split-Hand/foot Malformation 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.02 TP63 LBX1 DLX6 DLX5 BHLHA9

Sources for Split-Hand/foot Malformation 6

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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