CCF
MCID: CLB019
MIFTS: 43

Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly (CCF)

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

Aliases & Classifications for Clubfoot, Congenital, with or Without Deficiency of Long Bones...

MalaCards integrated aliases for Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly:

Name: Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly 57 72 13 6 39
Ccf 57 72
Hereditary Clubfoot Due to Pitx1 Point Mutation 58
Familial Clubfoot Due to Pitx1 Point Mutation 58
Hereditary Clubfoot Due to 5q31 Microdeletion 58
Familial Clubfoot Due to 5q31 Microdeletion 58
Talipes Equinovarus 72
Tev 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
incomplete penetrance
clubfoot is bilateral in most patients

Inheritance:
autosomal dominant


HPO:

31
clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly:
Inheritance autosomal dominant inheritance
Onset and clinical course incomplete penetrance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

OMIM® 57 119800
MeSH 44 D003025
ICD10 via Orphanet 33 Q66.8
MedGen 41 C0009081

Summaries for Clubfoot, Congenital, with or Without Deficiency of Long Bones...

UniProtKB/Swiss-Prot : 72 Clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly: A congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities. Clubfoot may occur in isolation or as part of a syndrome. Some patients present tibial hemimelia, bilateral patellar hypoplasia, and preaxial mirror-image polydactyly.

MalaCards based summary : Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly, also known as ccf, is related to polydactyly and clubfoot. An important gene associated with Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly is PITX1 (Paired Like Homeodomain 1). The drugs abobotulinumtoxinA and Botulinum Toxins have been mentioned in the context of this disorder. Affiliated tissues include bone, brain and skin, and related phenotypes are foot polydactyly and patellar hypoplasia

OMIM® : 57 Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012). (119800) (Updated 05-Apr-2021)

Related Diseases for Clubfoot, Congenital, with or Without Deficiency of Long Bones...

Diseases related to Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 119)
# Related Disease Score Top Affiliating Genes
1 polydactyly 30.1 PITX1 INPP5E CC2D2A
2 clubfoot 29.6 TRPV4 RYR1 PLOD2 PITX1 KIAA1109 KAT6B
3 scoliosis 29.2 TRPV4 RYR1 PLOD2 PITX1 COL5A1
4 tarp syndrome 11.9
5 crane-heise syndrome 11.4
6 al-gazali syndrome 11.3
7 vertical talus, congenital 11.2
8 popliteal pterygium syndrome 11.1
9 cyprus facial neuromusculoskeletal syndrome 11.1
10 dyssegmental dysplasia, silverman-handmaker type 11.1
11 pseudodiastrophic dysplasia 11.1
12 ehlers-danlos syndrome, musculocontractural type, 1 11.1
13 acromelic frontonasal dysostosis 11.1
14 chromosome 15q26-qter deletion syndrome 11.1
15 congestive heart failure 11.0
16 neural tube defects 10.4
17 benign idiopathic neonatal seizures 10.4
18 congenital amyoplasia 10.4
19 myelomeningocele 10.3
20 oligohydramnios 10.3
21 compartment syndrome 10.3
22 myotonic dystrophy 10.3
23 myotonic dystrophy 2 10.2
24 osteomyelitis 10.2
25 muscular atrophy 10.2
26 chromosomal triplication 10.2
27 glioma susceptibility 1 10.2
28 malignant astrocytoma 10.2
29 migraine with or without aura 1 10.2
30 headache 10.1
31 joubert syndrome 3 10.1 INPP5E CC2D2A
32 spondyloarthropathy 1 10.1
33 kabuki syndrome 1 10.1
34 moebius syndrome 10.1
35 ulnar-mammary syndrome 10.1
36 tarsal coalition 10.1
37 digeorge syndrome 10.1
38 down syndrome 10.1
39 hypogonadotropic hypogonadism 23 without anosmia 10.1
40 schwartz-jampel syndrome, type 1 10.1
41 paragangliomas 3 10.1
42 angiosarcoma 10.1
43 distal arthrogryposis 10.1
44 idiopathic scoliosis 10.1
45 ritscher-schinzel syndrome 10.1
46 muscular disease 10.1
47 hypospadias 10.1
48 hydrocephalus 10.1
49 hemiplegia 10.1
50 inflammatory spondylopathy 10.1

Graphical network of the top 20 diseases related to Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly:



Diseases related to Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly

Symptoms & Phenotypes for Clubfoot, Congenital, with or Without Deficiency of Long Bones...

Human phenotypes related to Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly:

31
# Description HPO Frequency HPO Source Accession
1 foot polydactyly 31 occasional (7.5%) HP:0001829
2 patellar hypoplasia 31 occasional (7.5%) HP:0003065
3 talipes equinovarus 31 HP:0001762

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal Feet:
talipes equinovarus (clubfoot)
oblique talus (in some patients)
preaxial mirror-image polydactyly (in some patients)

Skeletal Limbs:
tibial hemimelia (in some patients)
patellar hypoplasia, bilateral (in some patients)
no anomalies of upper limbs

Clinical features from OMIM®:

119800 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.76 CC2D2A COL5A1 INPP5E KIAA1109 PITX1 PLOD2
2 embryo MP:0005380 9.43 CC2D2A COL5A1 INPP5E KIAA1109 PITX1 PLOD2
3 integument MP:0010771 9.23 CC2D2A COL5A1 INPP5E KIAA1109 PITX1 PLOD2

Drugs & Therapeutics for Clubfoot, Congenital, with or Without Deficiency of Long Bones...

Drugs for Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 abobotulinumtoxinA
2 Botulinum Toxins
3 Botulinum Toxins, Type A

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Treatment of Idiopathic Clubfoot Utilizing Botulinum Toxin A: A New Treatment for Correction Unknown status NCT00152334 Botox
2 Genetic Linkage Study of Idiopathic Talipes Equinovarus (ITEV) (Clubfoot) Completed NCT00474344
3 A Double-Blind, Randomized Control Trial Comparing Botulinum Toxin Type A (Botox) and Placebo in the Treatment of Idiopathic Clubfoot Completed NCT00152347 Botox
4 Customized Orthosis for Children With Clubfoot Following Ponseti Casting Recruiting NCT03853811
5 Comparison of Ponseti Method Versus Older Treatments in Talipes Equinovarus Through Gait Analysis and Clinical Results Withdrawn NCT03580746

Search NIH Clinical Center for Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly

Genetic Tests for Clubfoot, Congenital, with or Without Deficiency of Long Bones...

Anatomical Context for Clubfoot, Congenital, with or Without Deficiency of Long Bones...

MalaCards organs/tissues related to Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly:

40
Bone, Brain, Skin, Eye, Spinal Cord, Heart, Kidney

Publications for Clubfoot, Congenital, with or Without Deficiency of Long Bones...

Articles related to Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly:

(show top 50) (show all 774)
# Title Authors PMID Year
1
Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly. 6 57
22258522 2012
2
Asymmetric lower-limb malformations in individuals with homeobox PITX1 gene mutation. 57 6
18950742 2008
3
Epidemiology of congenital idiopathic talipes equinovarus in Iowa, 1997-2005. 61 57
20583169 2010
4
Pedigree analysis and epidemiological features of idiopathic congenital talipes equinovarus in the United Kingdom: a case-control study. 57 61
17610748 2007
5
Genetics and epidemiology of idiopathic congenital talipes equinovarus. 61 57
12604963 2003
6
The role of major gene in clubfoot. 61 57
3358425 1988
7
FAMILY STUDIES AND THE CAUSE OF CONGENITAL CLUB FOOT. TALIPES EQUINOVARUS, TALIPES CALCANEO-VALGUS AND METATARSUS VARUS. 61 57
14216453 1964
8
KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis. 6
29290337 2018
9
Pitx1 haploinsufficiency causes clubfoot in humans and a clubfoot-like phenotype in mice. 57
21775501 2011
10
The genetics of idiopathic clubfoot. 57
12151881 2002
11
Genetics of club foot in Maori and Pacific people. 57
10978359 2000
12
Club foot in the Maori: a genetic study of 50 kindreds. 57
280791 1978
13
Genetic and epidemiological studies of clubfoot in Hawaii: ascertainment and incidence. 57
5365759 1969
14
Genetic and epidemiological studies of clubfoot in Hawaii. General and medical considerations. 57
5391957 1969
15
The causes of congenital club foot. 57
5830000 1965
16
Hereditary clubfoot. 57
5889122 1964
17
Gross motor skill development is similar in children post Ponseti casting for congenital talipes equinovarus compared to typically developing children: a systematic review. 61
33767125 2021
18
Talectomy for the Management of Resistant Talipes Equinovarus Deformity; Does Adding Ilizarov External Fixator Provide Extra Advantages? 61
33218863 2021
19
Prenatal Diagnosis of Acromelic Frontonasal Dysostosis. 61
33776626 2021
20
Co-occurrence of orofacial clefts and clubfoot phenotypes in a sub-Saharan African cohort: Whole-exome sequencing implicates multiple syndromes and genes. 61
33719213 2021
21
Birth prevalence of congenital anomalies in Argentina, according to socioeconomic level. 61
33786756 2021
22
Trisomy 5p with bilateral congenital diaphragmatic hernia: a case report. 61
33750440 2021
23
Sport Ability during Walking Age in Clubfoot-Affected Children after Ponseti Method: A Case-Series Study. 61
33804306 2021
24
Phenotypic spectrum of the RBM10-mediated intellectual disability and congenital malformation syndrome beyond classic TARP syndrome features. 61
33340101 2021
25
Chromosomal abnormality: Prevalence, prenatal diagnosis and associated anomalies based on a provincial-wide birth defects monitoring system. 61
33372274 2021
26
Bartsocas-Papas syndrome: The first case report of severe autosomal recessive form from Indonesia. 61
33529824 2021
27
Syndromic clubfoot beyond arthrogryposis and myelomeningocele: orthopedic treatment with Ponseti method. 61
33642245 2021
28
Functional Outcomes of Talectomy in Pediatric Feet. 61
33559504 2021
29
Genetic association and characterization of FSTL5 in isolated clubfoot. 61
33105483 2021
30
Congenital Talipes Equinovarus: Results of Treatment and Are We Bracing Effectively? 61
33573906 2021
31
Gene Environment Interactions Between the COL9A1 Gene and Maternal Drinking of Alcohol Contribute to the Risk of Congenital Talipes Equinovarus. 61
33372835 2021
32
The reliability and validity of the weight-bearing lunge test in a Congenital Talipes Equinovarus population (CTEV). 61
33505779 2021
33
Variations in arterial pedal circulation in idiopathic congenital talipes equinovarus: a systematic review. 61
32195760 2021
34
Blepharophimosis-ptosis-intellectual disability syndrome: A report of nine Egyptian patients with further expansion of phenotypic and mutational spectrum. 61
32949109 2020
35
Does malnutrition in clubfoot patients affect Ponseti technique and its outcome? 61
33345360 2020
36
Ultrasonographic Volumetric Assessment of Achilles Tendons in Unilateral Congenital Clubfoot in Lagos, Nigeria. 61
33185268 2020
37
Bone scan with SPECT/CT in children with complex foot and ankle pain: Initial experience of a paediatric tertiary referral centre. 61
33204351 2020
38
The role of clubfoot training programmes in low- and middle-income countries: a systematic review. 61
32571163 2020
39
Ponseti method of treating clubfoot - Is there difference if treatment is started before or after one month of age? 61
32918418 2020
40
Talipes Equinovarus Treatment in Infants Treated by the Ponseti Method Compared With Posterior-Only Release: A Mid-Childhood Comparison of Results. 61
32482579 2020
41
Talipes equinovarus or Clubfoot: A review of study approaches, management and trends in Pakistan. 61
32968421 2020
42
Integrated Bioinformatics Analysis Reveals Potential Pathway Biomarkers and Their Interactions for Clubfoot. 61
32829375 2020
43
Clubfoot deformity in the Solomon Islands: Melanesian versus Polynesian ethnicity, a retrospective cohort study. 61
32874360 2020
44
Management issues of congenital talipes equinovarus in the neonatal intensive care unit: A systematic review. 61
32958391 2020
45
In-toeing gait in children with clubfoot and the effect of tibial rotation osteotomy. 61
31651746 2020
46
Evaluation of genetic susceptibility of common variants in SOX9 in patients with congenital talipes equinovarus in the Han Chinese population. 61
32703248 2020
47
Global prevalence estimates of three chronic musculoskeletal conditions: club foot, juvenile idiopathic arthritis and juvenile systemic lupus erythematosus. 61
32532304 2020
48
Prenatal clubfoot increases the risk for clinically significant chromosomal microarray results - Analysis of 269 singleton pregnancies. 61
32339917 2020
49
Arthrogryposis is a descriptive term, not a specific disease entity: escobar syndrome is an Example. 61
32536119 2020
50
Cross-cultural adaptation, validity and reliability of Turkish version of Oxford Ankle Foot Questionnaire for children with congenital talipes equinovarus. 61
32620389 2020

Variations for Clubfoot, Congenital, with or Without Deficiency of Long Bones...

ClinVar genetic disease variations for Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly:

6 (show all 24)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PITX1 NM_002653.5(PITX1):c.388G>A (p.Glu130Lys) SNV Pathogenic 7505 rs121909109 GRCh37: 5:134366980-134366980
GRCh38: 5:135031290-135031290
2 PITX1 NM_002653.5(PITX1):c.765_799del (p.Ala256fs) Deletion Pathogenic 37253 rs730882191 GRCh37: 5:134364615-134364649
GRCh38: 5:135028925-135028959
3 INPP5E NM_019892.6(INPP5E):c.1132C>T (p.Arg378Cys) SNV Pathogenic 400 rs121918130 GRCh37: 9:139327634-139327634
GRCh38: 9:136433182-136433182
4 CC2D2A NM_001080522.2(CC2D2A):c.1149+1G>A SNV Pathogenic 523401 rs1553827236 GRCh37: 4:15518380-15518380
GRCh38: 4:15516757-15516757
5 CC2D2A NM_001080522.2(CC2D2A):c.4179+1del Deletion Pathogenic 56312 rs386833760 GRCh37: 4:15589552-15589552
GRCh38: 4:15587929-15587929
6 DARS2 NM_018122.5(DARS2):c.492+2T>C SNV Pathogenic 1062 rs142433332 GRCh37: 1:173800770-173800770
GRCh38: 1:173831632-173831632
7 TRPV4 NM_021625.4(TRPV4):c.947G>A (p.Arg316His) SNV Pathogenic 30473 rs387906905 GRCh37: 12:110236624-110236624
GRCh38: 12:109798819-109798819
8 DARS2 NM_018122.5(DARS2):c.228-21_228-20delinsC Indel Pathogenic 1057 rs1553201258 GRCh37: 1:173797450-173797451
GRCh38: 1:173828312-173828313
9 RYR1 NM_000540.2(RYR1):c.7268T>A (p.Met2423Lys) SNV Pathogenic 12989 rs118192174 GRCh37: 19:38990601-38990601
GRCh38: 19:38499961-38499961
10 DUSP29 , KAT6B NM_012330.4(KAT6B):c.5213C>T (p.Thr1738Ile) SNV Likely pathogenic 523500 rs1554846212 GRCh37: 10:76789795-76789795
GRCh38: 10:75030037-75030037
11 PITX1 NM_002653.5(PITX1):c.414G>T (p.Lys138Asn) SNV Likely pathogenic 1033526 GRCh37: 5:134365000-134365000
GRCh38: 5:135029310-135029310
12 KIAA1109 NM_001384125.1(KIAA1109):c.3323+1G>A SNV Likely pathogenic 978640 GRCh37: 4:123151367-123151367
GRCh38: 4:122230212-122230212
13 KIAA1109 NM_001384125.1(KIAA1109):c.692del (p.Phe231fs) Deletion Likely pathogenic 978675 GRCh37: 4:123109112-123109112
GRCh38: 4:122187957-122187957
14 PLOD2 NM_182943.3(PLOD2):c.2038C>T (p.Arg680Ter) SNV Likely pathogenic 374012 rs780770356 GRCh37: 3:145788912-145788912
GRCh38: 3:146071125-146071125
15 KIAA1109 NM_015312.3(KIAA1109):c.1557T>A (p.Tyr519Ter) SNV Likely pathogenic 183349 rs730882245 GRCh37: 4:123128323-123128323
GRCh38: 4:122207168-122207168
16 PLOD2 NM_182943.3(PLOD2):c.1361G>T (p.Gly454Val) SNV Likely pathogenic 374011 rs778360818 GRCh37: 3:145797042-145797042
GRCh38: 3:146079255-146079255
17 COL5A1 NM_001278074.1(COL5A1):c.2903del (p.Pro968fs) Deletion Likely pathogenic 374067 rs1057518871 GRCh37: 9:137690256-137690256
GRCh38: 9:134798410-134798410
18 PITX1 NM_002653.5(PITX1):c.683G>T (p.Ser228Ile) SNV Uncertain significance 930834 GRCh37: 5:134364731-134364731
GRCh38: 5:135029041-135029041
19 UNC13C NM_001080534.3(UNC13C):c.283C>T (p.Arg95Ter) SNV Uncertain significance 982686 GRCh37: 15:54305383-54305383
GRCh38: 15:54013186-54013186
20 AARS1 NM_001605.2(AARS1):c.2054T>C (p.Val685Ala) SNV Uncertain significance 523443 rs1555539904 GRCh37: 16:70292059-70292059
GRCh38: 16:70258156-70258156
21 PKD1 NM_001009944.3(PKD1):c.12014A>G (p.Gln4005Arg) SNV Uncertain significance 523352 rs760873748 GRCh37: 16:2140799-2140799
GRCh38: 16:2090798-2090798
22 PKD1 NM_001009944.3(PKD1):c.7429C>T (p.Arg2477Cys) SNV Uncertain significance 257000 rs376283361 GRCh37: 16:2156459-2156459
GRCh38: 16:2106458-2106458
23 TNFRSF13B NM_012452.2(TNFRSF13B):c.310T>C (p.Cys104Arg) SNV Uncertain significance 5302 rs34557412 GRCh37: 17:16852187-16852187
GRCh38: 17:16948873-16948873
24 VANGL1 NM_138959.3(VANGL1):c.523C>T (p.Arg175Trp) SNV Uncertain significance 167818 rs142594314 GRCh37: 1:116206600-116206600
GRCh38: 1:115663979-115663979

UniProtKB/Swiss-Prot genetic disease variations for Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly:

72
# Symbol AA change Variation ID SNP ID
1 PITX1 p.Glu130Lys VAR_058113 rs121909109

Expression for Clubfoot, Congenital, with or Without Deficiency of Long Bones...

Search GEO for disease gene expression data for Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly.

Pathways for Clubfoot, Congenital, with or Without Deficiency of Long Bones...

GO Terms for Clubfoot, Congenital, with or Without Deficiency of Long Bones...

Biological processes related to Clubfoot, Congenital, with or Without Deficiency of Long Bones and/or Mirror-Image Polydactyly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 skin development GO:0043588 8.62 RYR1 COL5A1

Sources for Clubfoot, Congenital, with or Without Deficiency of Long Bones...

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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