SHFM
MCID: ISL121
MIFTS: 42

Isolated Split Hand-Split Foot Malformation (SHFM)

Categories: Bone diseases, Fetal diseases, Rare diseases

Aliases & Classifications for Isolated Split Hand-Split Foot Malformation

MalaCards integrated aliases for Isolated Split Hand-Split Foot Malformation:

Name: Isolated Split Hand-Split Foot Malformation 58
Ectrodactyly 58 70
Split Hand Foot Malformation 58
Split-Hand/foot Malformation 70
Split Hand Foot Deformity 1 70
Split Hand Foot Deformity 70
Shfm 58

Characteristics:

Orphanet epidemiological data:

58
isolated split hand-split foot malformation
Inheritance: Autosomal dominant,Autosomal recessive,X-linked recessive; Prevalence: 1-9/100000 (Europe); Age of onset: Infancy,Neonatal;

Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

ICD10 via Orphanet 33 Q71.6 Q72.7
UMLS via Orphanet 71 C0265554
Orphanet 58 ORPHA2440
UMLS 70 C0265554 C2699510 C2931018 more

Summaries for Isolated Split Hand-Split Foot Malformation

MalaCards based summary : Isolated Split Hand-Split Foot Malformation, also known as ectrodactyly, is related to split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive and split-hand/foot malformation 6. An important gene associated with Isolated Split Hand-Split Foot Malformation is WNT10B (Wnt Family Member 10B), and among its related pathways/superpathways is MECP2 and Associated Rett Syndrome. Affiliated tissues include bone marrow, bone and tongue, and related phenotypes are oligodactyly and finger syndactyly

Related Diseases for Isolated Split Hand-Split Foot Malformation

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

(show top 50) (show all 259)
# Related Disease Score Top Affiliating Genes
1 split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive 32.2 WNT10B TP63 SEM1 DLX6 DLX5
2 split-hand/foot malformation 6 30.1 WNT10B TP63 SEM1 EPS15L1 DLX6 DLX5
3 orofacial cleft 29.9 TP63 DLX6 DLX5
4 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 29.8 WNT10B TP63 DLX6 DLX5
5 cleft palate, isolated 29.7 TP63 DLX6 DLX5
6 split hand-foot malformation 29.7 WNT10B TP63 SEM1 MAP3K20-AS1 MAP3K20 DLX6
7 chromosome 2q35 duplication syndrome 29.7 WNT10B TP63 SEM1 DLX6 DLX5
8 split-hand/foot malformation 1 29.5 TP63 SEM1 MAP3K20-AS1 MAP3K20 DLX5
9 tooth agenesis 29.5 WNT10B TP63 DLX5
10 rapp-hodgkin syndrome 29.5 TP63 DLX6 DLX5
11 split-hand/foot malformation 3 29.0 SEM1 DLX6 DLX5 BTRC
12 split-hand/foot malformation 5 28.9 TP63 SEM1 DLX6 DLX5
13 split-hand/foot malformation 2 28.9 WNT10B TP63 SEM1 DLX6 DLX5
14 split-hand/foot malformation 4 28.6 WNT10B TP63 SEM1 EPS15L1 DLX6 DLX5
15 split-hand/foot malformation with long bone deficiency 2 11.6
16 ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome 11.6
17 hartsfield syndrome 11.6
18 microphthalmia, syndromic 8 11.5
19 cleft palate, cardiac defect, genital anomalies, and ectrodactyly 11.4
20 brachydactyly-ectrodactyly with fibular aplasia or hypoplasia 11.4
21 split-hand/foot malformation with long bone deficiency 1 11.3
22 femur bifid with monodactylous ectrodactyly 11.3
23 intellectual disability-spasticity-ectrodactyly syndrome 11.3
24 triphalangeal thumbs with brachyectrodactyly 11.2
25 split-foot deformity with mandibulofacial dysostosis 11.2
26 ectrodactyly and ectodermal dysplasia without cleft lip/palate 11.2
27 ectrodactyly-polydactyly 11.2
28 ectrodactyly cardiopathy dysmorphism 11.1
29 anonychia-onychodystrophy with brachydactyly type b and ectrodactyly 11.1
30 phocomelia ectrodactyly deafness sinus arrhythmia 11.1
31 anonychia-ectrodactyly 11.1
32 femur, unilateral bifid, with monodactylous ectrodactyly 11.1
33 focal dermal hypoplasia 11.1
34 phocomelia-ectrodactyly, ear malformation, deafness, and sinus arrhythmia 11.1
35 ectrodactyly-cleft palate syndrome 11.0
36 tibial aplasia-ectrodactyly syndrome 11.0
37 limb defects, distal transverse, with mental retardation and spasticity 11.0
38 kasznica carlson coppedge syndrome 11.0
39 split-hand with congenital nystagmus, fundal changes, and cataracts 11.0
40 ectrodactyly of lower limbs, congenital heart defect, and micrognathia 10.9
41 jones hersh yusk syndrome 10.9
42 landy-donnai syndrome 10.9
43 saal bulas syndrome 10.9
44 adams-oliver syndrome 1 10.8
45 ectrodactyly with and without other manifestations 10.8
46 ankyloblepharon-ectodermal defects-cleft lip/palate 10.8
47 fibular aplasia, tibial campomelia, and oligosyndactyly syndrome 10.8
48 adams-oliver syndrome 2 10.8
49 adams-oliver syndrome 3 10.8
50 adams-oliver syndrome 4 10.8

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



Diseases related to Isolated Split Hand-Split Foot Malformation

Symptoms & Phenotypes for Isolated Split Hand-Split Foot Malformation

Human phenotypes related to Isolated Split Hand-Split Foot Malformation:

58 31 (show all 6)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 oligodactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0012165
2 finger syndactyly 58 31 frequent (33%) Frequent (79-30%) HP:0006101
3 sensorineural hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000407
4 split hand 58 31 occasional (7.5%) Occasional (29-5%) HP:0001171
5 absent hand 58 31 occasional (7.5%) Occasional (29-5%) HP:0004050
6 aniridia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000526

MGI Mouse Phenotypes related to Isolated Split Hand-Split Foot Malformation:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.35 BTRC DLX5 DLX6 TP63 WNT10B
2 limbs/digits/tail MP:0005371 9.02 DLX5 DLX6 EPS15L1 MAP3K20 TP63

Drugs & Therapeutics for Isolated Split Hand-Split Foot Malformation

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Randomized Controlled Trial to Compare the Effects of Single Versus Repeated Intracoronary Application of Autologous Bone Marrow-derived Mononuclear Cells on Total and SHFM-predicted Mortality in Patients With Chronic Post-infarction Heart Failure Active, not recruiting NCT01693042 Phase 2, Phase 3

Search NIH Clinical Center for Isolated Split Hand-Split Foot Malformation

Genetic Tests for Isolated Split Hand-Split Foot Malformation

Anatomical Context for Isolated Split Hand-Split Foot Malformation

MalaCards organs/tissues related to Isolated Split Hand-Split Foot Malformation:

40
Bone Marrow, Bone, Tongue, Eye, Skin, Pituitary, Thymus

Publications for Isolated Split Hand-Split Foot Malformation

Articles related to Isolated Split Hand-Split Foot Malformation:

(show top 50) (show all 717)
# 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. 61 6
25196357 2014
2
Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation. 61 6
24496061 2014
3
Isolated ectrodactyly caused by a heterozygous missense mutation in the transactivation domain of TP63. 6 61
15736220 2005
4
Split-hand/split-foot malformation is caused by mutations in the p63 gene on 3q27. 6 61
10839977 2000
5
Split hand-foot malformation and a novel WNT10B mutation. 6
29427788 2018
6
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
7
Homozygous nonsense mutation in WNT10B and sporadic split-hand/foot malformation (SHFM) with autosomal recessive inheritance. 6
20635353 2010
8
Homozygous WNT10b mutation and complex inheritance in Split-Hand/Foot Malformation. 6
18515319 2008
9
Evidence for autosomal recessive inheritance of split hand/split foot malformation: a report of nine cases. 6
12072797 2002
10
Anomalous inheritance in a kindred with split hand, split foot malformation. 6
3366140 1988
11
Four Unusual Cases of Congenital Forelimb Malformations in Dogs. 61
33799336 2021
12
The power of zebrafish models for understanding the co-occurrence of craniofacial and limb disorders. 61
33393730 2021
13
Cleft Lip and Palate in Ectodermal Dysplasia. 61
32864997 2021
14
Digital Transfer for Hand Reconstruction in Cleft Hand and Foot Differences. 61
33598896 2021
15
Isoform-Specific Roles of Mutant p63 in Human Diseases. 61
33572532 2021
16
Depiction of ectrodactyly, sirenomelian and cyclopia in a figure by Hokusai. 61
33135837 2020
17
Genotype-phenotype correlations of UBA2 mutations in patients with ectrodactyly. 61
32758660 2020
18
TP63-mutation as a cause of prenatal lethal multicystic dysplastic kidneys. 61
32881366 2020
19
The prenatal diagnosis and genetic counseling of chromosomal micro-duplication on 10q24.3 in a fetus: A case report and a brief review of the literature. 61
33080687 2020
20
EEC-LM-ADULT syndrome caused by R319H mutation in TP63 with ectrodactyly, syndactyly, and teeth anomaly: A case report. 61
33126320 2020
21
Sequence Variants in the WNT10B and TP63 Genes Underlying Isolated Split-Hand/Split-Foot Malformation. 61
32762550 2020
22
Ectrodactyly-ectodermal dysplasia-clefting syndrome presenting with bilateral choanal atresia and rectal stenosis. 61
32476291 2020
23
Endocrinological Features of Hartsfield Syndrome in an Adult Patient With a Novel Mutation of FGFR1. 61
32373773 2020
24
Developmental glaucoma in a patient of ectrodactyly-ectodermal dysplasia. 61
32317482 2020
25
Prenatal diagnosis of Klippel-Trenaunay syndrome: Series of four cases and review of the literature. 61
32528545 2020
26
Novel phenotype of syndromic premature ovarian insufficiency associated with TP63 molecular defect. 61
32067224 2020
27
Split hand/foot malformation associated with 20p12.1 deletion: A case report. 61
31698100 2020
28
Surgical Ectrodactyly Repair Using Limb-lengthening and Bone Tissue Engineering Techniques in a Toy Dog Breed. 61
32111789 2020
29
Cleft foot: A case report and review of literature. 61
32190557 2020
30
Goltz-Gorlin syndrome: a rare cause of ectrodactyly. 61
31563885 2020
31
[Identification of a Tp63 gene variant in an abortus with Ectrodactyly, Ectodermal dysplasia, Cleft lip/palate syndrome by whole-exome sequencing]. 61
32034739 2020
32
Outcomes of primary powered endoscopic dacryocystorhinostomy in syndromic congenital nasolacrimal duct obstruction. 61
30892112 2020
33
Ectrodactyly-Ectodermal Dysplasia Clefting Syndrome: A Case Report of Its Dental Management with 2 Years Follow-Up. 61
32257456 2020
34
Amniotic Band Syndrome with Ectrodactyly-Two Cases. 61
32055521 2020
35
Improvement of epidermal covering on AEC patients with severe skin erosions by PRIMA-1MET/APR-246. 61
31949132 2020
36
[Surgical Treatment of Congenital Cleft Foot - Case Study and Literature Review]. 61
32131973 2020
37
Deletion 7q21.2-q22.1 in a case with split hand-split foot malformation, sensorineural hearing loss and intellectual disability: Phenotype subtypes and the correlation with genotypes. 61
30543991 2019
38
Novel synonymous and missense variants in FGFR1 causing Hartsfield syndrome. 61
31512363 2019
39
[Ectrodactyly ectodermal dysplasia-cleft lip/palate syndrome: a case report]. 61
31683385 2019
40
A novel mutation (c.1010G>T; p.R337L) in TP63 as a cause of split-hand/foot malformation with hypodontia. 61
31420900 2019
41
Single-cell RNA-seq identifies a reversible mesodermal activation in abnormally specified epithelia of p63 EEC syndrome. 61
31413199 2019
42
Morphological abnormalities in natural populations of the common South American toad Rhinella arenarum inhabiting fluoride-rich environments. 61
30959310 2019
43
[Congenital ectrodactyly caused by chromosome 10q24.31 duplication and its pathogenetic analysis]. 61
31447422 2019
44
A novel dominant-negative FGFR1 variant causes Hartsfield syndrome by deregulating RAS/ERK1/2 pathway. 61
30787447 2019
45
Tooth defects of EEC and AEC syndrome caused by heterozygous TP63 mutations in three Chinese families and genotype-phenotype correlation analyses of TP63-related disorders. 61
31050217 2019
46
Split hand/foot malformation with long bone deficiency associated with BHLHA9 gene duplication: a case report and review of literature. 61
31200655 2019
47
Ectrodactyly-ectodermal dysplasia-clefting syndrome with unusual cutaneous vitiligoid and psoriasiform lesions due to a novel single point TP63 gene mutation. 61
31333354 2019
48
Staged ocular fornix reconstruction for glaucoma drainage device under neoconjunctiva at the time of Boston type 1 Keratoprosthesis implantation. 61
30742989 2019
49
Lower Extremity Surgical Treatment to Improve Function in a Patient with Gollop-Wolfgang Complex: A Case Report. 61
31211748 2019
50
Split Hand Foot Malformation Syndrome: A Novel Heterozygous FGFR1 Mutation Detected by Next Generation Sequencing. 61
31929729 2019

Variations for Isolated Split Hand-Split Foot Malformation

ClinVar genetic disease variations for Isolated Split Hand-Split Foot Malformation:

6 (show all 20)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 WNT10B NM_003394.4(WNT10B):c.994C>T (p.Arg332Trp) SNV Pathogenic 7630 rs121918349 GRCh37: 12:49360054-49360054
GRCh38: 12:48966271-48966271
2 MAP3K20-AS1 , MAP3K20 NM_016653.3(MAP3K20):c.1103T>G (p.Phe368Cys) SNV Pathogenic 218144 rs863225437 GRCh37: 2:174097087-174097087
GRCh38: 2:173232359-173232359
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.817del (p.Ala273fs) Deletion Pathogenic 634645 GRCh37: 12:49360231-49360231
GRCh38: 12:48966448-48966448
5 WNT10B NM_003394.4(WNT10B):c.458_461dup (p.Asp155fs) Duplication Pathogenic 30237 rs763548858 GRCh37: 12:49361978-49361979
GRCh38: 12:48968195-48968196
6 TP63 NM_003722.5(TP63):c.697A>G (p.Lys233Glu) SNV Pathogenic 6531 rs121908838 GRCh37: 3:189582138-189582138
GRCh38: 3:189864349-189864349
7 TP63 NM_003722.5(TP63):c.955C>T (p.Arg319Cys) SNV Pathogenic 6532 rs121908839 GRCh37: 3:189585694-189585694
GRCh38: 3:189867905-189867905
8 TP63 NM_003722.5(TP63):c.289C>T (p.Arg97Cys) SNV Pathogenic 6549 rs121908848 GRCh37: 3:189456528-189456528
GRCh38: 3:189738739-189738739
9 DLX5 NM_005221.6(DLX5):c.558G>T (p.Gln186His) SNV Pathogenic 91861 rs398122527 GRCh37: 7:96650360-96650360
GRCh38: 7:97021048-97021048
10 DLX5 NM_005221.6(DLX5):c.115G>T (p.Glu39Ter) SNV Pathogenic 156469 rs587777842 GRCh37: 7:96653821-96653821
GRCh38: 7:97024509-97024509
11 WNT10B NM_003394.4(WNT10B):c.817dup (p.Ala273fs) Duplication Pathogenic 634647 GRCh37: 12:49360230-49360231
GRCh38: 12:48966447-48966448
12 overlap with 67 genes GRCh37/hg19 7q21.2-22.1(chr7:92445452-99686985)x1 copy number loss Pathogenic 545583 GRCh37: 7:92445452-99686985
GRCh38:
13 WNT10B NM_003394.4(WNT10B):c.505C>T (p.Arg169Ter) SNV Pathogenic 1029700 GRCh37: 12:49361935-49361935
GRCh38: 12:48968152-48968152
14 WNT10B NM_003394.4(WNT10B):c.338-1G>C SNV Pathogenic/Likely pathogenic 545118 rs1163162816 GRCh37: 12:49362103-49362103
GRCh38: 12:48968320-48968320
15 WNT10B NM_003394.4(WNT10B):c.746G>T (p.Cys249Phe) SNV Likely pathogenic 634646 GRCh37: 12:49360302-49360302
GRCh38: 12:48966519-48966519
16 WNT10B NM_003394.4(WNT10B):c.949T>A (p.Phe317Ile) SNV Likely pathogenic 634648 GRCh37: 12:49360099-49360099
GRCh38: 12:48966316-48966316
17 WNT10B NM_003394.4(WNT10B):c.257A>C (p.Gln86Pro) SNV Likely pathogenic 638164 rs1592252556 GRCh37: 12:49363952-49363952
GRCh38: 12:48970169-48970169
18 WNT10B NM_003394.4(WNT10B):c.676C>T (p.Arg226Ter) SNV Likely pathogenic 522440 rs763991433 GRCh37: 12:49361764-49361764
GRCh38: 12:48967981-48967981
19 WNT10B NM_003394.4(WNT10B):c.290T>C (p.Leu97Pro) SNV Uncertain significance 623323 rs1458667581 GRCh37: 12:49363919-49363919
GRCh38: 12:48970136-48970136
20 TP63 NM_003722.5(TP63):c.1825G>A (p.Glu609Lys) SNV Uncertain significance 69817 rs142762485 GRCh37: 3:189612073-189612073
GRCh38: 3:189894284-189894284

Expression for Isolated Split Hand-Split Foot Malformation

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

Pathways for Isolated Split Hand-Split Foot Malformation

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

# Super pathways Score Top Affiliating Genes
1 10.42 DLX6 DLX5

GO Terms for Isolated Split Hand-Split Foot Malformation

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

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 cell differentiation GO:0030154 9.81 TP63 MAP3K20 DLX6 DLX5
2 regulation of mitotic cell cycle phase transition GO:1901990 9.56 SEM1 BTRC
3 cellular response to organic cyclic compound GO:0071407 9.55 WNT10B BTRC
4 positive regulation of osteoblast differentiation GO:0045669 9.54 WNT10B TP63
5 positive regulation of canonical Wnt signaling pathway GO:0090263 9.54 WNT10B SEM1 DLX5
6 NIK/NF-kappaB signaling GO:0038061 9.52 SEM1 BTRC
7 roof of mouth development GO:0060021 9.49 DLX6 DLX5
8 positive regulation of epithelial cell proliferation GO:0050679 9.48 DLX6 DLX5
9 inner ear morphogenesis GO:0042472 9.46 DLX6 DLX5
10 stress-activated MAPK cascade GO:0051403 9.43 MAP3K20 BTRC
11 skeletal system development GO:0001501 9.43 TP63 DLX6 DLX5
12 head development GO:0060322 9.4 DLX6 DLX5
13 epithelial cell differentiation GO:0030855 9.33 TP63 DLX6 DLX5
14 embryo development GO:0009790 9.32 DLX6 DLX5
15 embryonic limb morphogenesis GO:0030326 9.13 TP63 DLX6 DLX5
16 anatomical structure formation involved in morphogenesis GO:0048646 8.8 TP63 DLX6 DLX5

Sources for Isolated Split Hand-Split Foot Malformation

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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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