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 56 73 13 39
Talipes Equinovarus 73 32
Ccf 56 73
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
Tev 73

Characteristics:

OMIM:

56
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 56 119800
MeSH 43 D003025
ICD10 32 Q66.0
ICD10 via Orphanet 33 Q66.8
MedGen 41 C0009081

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

UniProtKB/Swiss-Prot : 73 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 talipes equinovarus, 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 Acetylcholine and abobotulinumtoxinA 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 : 56 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)

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 103)
# Related Disease Score Top Affiliating Genes
1 polydactyly 30.1 PITX1 INPP5E CC2D2A
2 clubfoot 29.8 TRPV4 TNFRSF13B RYR1 PLOD2 PITX1 KIAA1109
3 scoliosis 28.6 TRPV4 RYR1 PLOD2 PITX1
4 tarp syndrome 12.5
5 vertical talus, congenital 11.8
6 crane-heise syndrome 11.7
7 popliteal pterygium syndrome 11.4
8 cyprus facial neuromusculoskeletal syndrome 11.4
9 dyssegmental dysplasia, silverman-handmaker type 11.4
10 pseudodiastrophic dysplasia 11.4
11 ehlers-danlos syndrome, musculocontractural type, 1 11.4
12 acromelic frontonasal dysostosis 11.4
13 al-gazali syndrome 11.4
14 chromosome 15q26-qter deletion syndrome 11.4
15 congestive heart failure 11.3
16 benign idiopathic neonatal seizures 10.7
17 neural tube defects 10.6
18 alkuraya-kucinskas syndrome 10.5
19 congenital amyoplasia 10.5
20 multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly 10.5
21 myelomeningocele 10.5
22 oligohydramnios 10.5
23 compartment syndrome 10.5
24 myotonic dystrophy 10.5
25 osteomyelitis 10.4
26 muscular atrophy 10.4
27 47,xyy 10.4
28 chromosomal triplication 10.4
29 human immunodeficiency virus type 1 10.3
30 spondyloarthropathy 1 10.2
31 aortic valve disease 1 10.2
32 kabuki syndrome 1 10.2
33 moebius syndrome 10.2
34 ulnar-mammary syndrome 10.2
35 tarsal coalition 10.2
36 digeorge syndrome 10.2
37 down syndrome 10.2
38 hypogonadotropic hypogonadism 23 without anosmia 10.2
39 schwartz-jampel syndrome, type 1 10.2
40 paragangliomas 3 10.2
41 angiosarcoma 10.2
42 distal arthrogryposis 10.2
43 idiopathic scoliosis 10.2
44 ritscher-schinzel syndrome 10.2
45 muscular disease 10.2
46 hypospadias 10.2
47 hydrocephalus 10.2
48 hemiplegia 10.2
49 inflammatory spondylopathy 10.2
50 gout 10.2

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:

56
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

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

45
# Description MGI Source Accession Score Top Affiliating Genes
1 integument MP:0010771 9.55 CC2D2A KIAA1109 PITX1 RYR1 TRPV4
2 limbs/digits/tail MP:0005371 9.26 CC2D2A INPP5E PITX1 RYR1
3 mortality/aging MP:0010768 9.23 CC2D2A DARS2 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):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcholine Approved, Investigational 51-84-3 187
2 abobotulinumtoxinA
3 Botulinum Toxins
4 Botulinum Toxins, Type A
5 Cholinergic Agents
6 Neurotransmitter Agents

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 The Pma Mouse and the Developmental Basis of Clubfoot: MRI Anatomical Modelling of Human ICTEV (Clubfoot) Completed NCT01088828
4 A Double-Blind, Randomized Control Trial Comparing Botulinum Toxin Type A (Botox) and Placebo in the Treatment of Idiopathic Clubfoot Completed NCT00152347 Botox
5 Genetic and Clinical Studies of Congenital Anomaly Syndromes Completed NCT00001404
6 Clubfoot DNA Repository Completed NCT00607191
7 Customized Orthosis for Children With Clubfoot Following Ponseti Casting Recruiting NCT03853811
8 Efficacy of Botox in Patients With Idiopathic Clubfoot Recruiting NCT00474032 Botulinum Toxin (Type A) injection (10 U/Kg)
9 Trial Readiness and Endpoint Assessment in Congenital Myotonic Dystrophy Suspended NCT03059264
10 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 739)
# Title Authors PMID Year
1
Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly. 6 56
22258522 2012
2
Asymmetric lower-limb malformations in individuals with homeobox PITX1 gene mutation. 56 6
18950742 2008
3
Epidemiology of congenital idiopathic talipes equinovarus in Iowa, 1997-2005. 56 61
20583169 2010
4
Pedigree analysis and epidemiological features of idiopathic congenital talipes equinovarus in the United Kingdom: a case-control study. 56 61
17610748 2007
5
Genetics and epidemiology of idiopathic congenital talipes equinovarus. 56 61
12604963 2003
6
The role of major gene in clubfoot. 56 61
3358425 1988
7
FAMILY STUDIES AND THE CAUSE OF CONGENITAL CLUB FOOT. TALIPES EQUINOVARUS, TALIPES CALCANEO-VALGUS AND METATARSUS VARUS. 61 56
14216453 1964
8
Pitx1 haploinsufficiency causes clubfoot in humans and a clubfoot-like phenotype in mice. 56
21775501 2011
9
The genetics of idiopathic clubfoot. 56
12151881 2002
10
Genetics of club foot in Maori and Pacific people. 56
10978359 2000
11
Club foot in the Maori: a genetic study of 50 kindreds. 56
280791 1978
12
Genetic and epidemiological studies of clubfoot in Hawaii: ascertainment and incidence. 56
5365759 1969
13
Genetic and epidemiological studies of clubfoot in Hawaii. General and medical considerations. 56
5391957 1969
14
The causes of congenital club foot. 56
5830000 1965
15
Hereditary clubfoot. 56
5889122 1964
16
In-toeing gait in children with clubfoot and the effect of tibial rotation osteotomy. 61
31651746 2020
17
Prenatal clubfoot increases the risk for clinically significant chromosomal microarray results - Analysis of 269 singleton pregnancies. 61
32339917 2020
18
Global prevalence estimates of three chronic musculoskeletal conditions: club foot, juvenile idiopathic arthritis and juvenile systemic lupus erythematosus. 61
32532304 2020
19
The role of clubfoot training programmes in low- and middle-income countries: a systematic review. 61
32571163 2020
20
Arthrogryposis is a descriptive term, not a specific disease entity: escobar syndrome is an Example. 61
32536119 2020
21
Whole‑exome sequencing study identifies two novel rare variations associated with congenital talipes equinovarus. 61
32236576 2020
22
Interventions for congenital talipes equinovarus (clubfoot). 61
32412098 2020
23
Talipes Equinovarus Treatment in Infants Treated by the Ponseti Method Compared With Posterior-Only Release: A Mid-Childhood Comparison of Results. 61
32482579 2020
24
DSE associated musculocontractural EDS, a milder phenotype or phenotypic variability. 61
31655143 2020
25
Orthopedic findings in arthrogryposis and congenital Zika syndrome: A case series. 61
31891236 2020
26
Variations in arterial pedal circulation in idiopathic congenital talipes equinovarus: a systematic review. 61
32195760 2020
27
Epidemiology of birth defects based on a birth defect surveillance system in Southern Jiangsu, China, 2014-2018. 61
32098533 2020
28
Forefoot malformations, deformities and other congenital defects in children. 61
31648997 2020
29
Brace Yourselves: Outcomes of Ponseti Casting and Foot Abduction Orthosis Bracing in Idiopathic Congenital Talipes Equinovarus. 61
30969199 2020
30
Calpainopathy: Description of a Novel Mutation and Clinical Presentation with Early Severe Contractures. 61
31991774 2020
31
Integrated bioinformatics analysis of potential pathway biomarkers using abnormal proteins in clubfoot. 61
31998564 2020
32
Septo-optic dysplasia with amniotic band syndrome sequence: a case report. 61
31839004 2019
33
Congenital talipes equinovarus (clubfoot). 61
31787157 2019
34
Conjoined twins presenting with foot deformities: insights to management and challenges. 61
31826902 2019
35
The Validity of Patient-reported Outcome Measurement Information System (PROMIS) Parent Proxy Instruments to Assess Function in Children With Talipes Equinovarus. 61
30913133 2019
36
Simultaneous lateral column shortening along with differential distraction by Joshi's external stabilization system for rigid neglected clubfoot correction. 61
30702637 2019
37
Factors Related to Early Recurrence of Idiopathic Clubfoot Post the Ponseti Method. 61
31890107 2019
38
[Surgical treatment of limb deformity and disability: a statistical analysis of 35 075 cases from QIN Sihe orthopaedic team between May 25, 1978 and December 31, 2018]. 61
31650744 2019
39
A hospital-based birth defects surveillance system in Kampala, Uganda. 61
31640605 2019
40
HOXA9 rs3801776 G>A polymorphism increases congenital talipes equinovarus risk in a Chinese population. 61
31424148 2019
41
Does idiopathic congenital talipes equinovarus have an impact on attainment of developmental milestones? A multicentre international study. 61
31489040 2019
42
A polyaxial fixation brace for the treatment of idiopathic congenital talipes equinovarus in newborns. 61
31300013 2019
43
Congenital talipes equinovarus: a systematic review of relapse as a primary outcome of the Ponseti method. 61
31154846 2019
44
A new unilateral abduction orthosis for Ponseti-treated clubfoot: A cohort study to assess compliance. 61
30557091 2019
45
TARP syndrome: Long-term survival, anatomic patterns of congenital heart defects, differential diagnosis and pathogenetic considerations. 61
30189253 2019
46
Accelerated Ponseti method: First experiences in a more convenient technique for patients with severe idiopathic club feet. 61
30930070 2019
47
Osteomyelitis Secondary to Ponseti Method for the Treatment of Clubfoot Associated with Meningomyelocele. 61
31183281 2019
48
The top 100 most-cited articles on 'Clubfoot'. 61
30204625 2019
49
Case report of a child bearing a novel deleterious splicing variant in PIGT. 61
30813157 2019
50
Experience of treating the Talipes equinovarus deformity with Ponsetti technique at district level. 61
30697014 2019

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 21) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CC2D2A NM_001080522.2(CC2D2A):c.1149+1G>ASNV Pathogenic 523401 rs1553827236 4:15518380-15518380 4:15516757-15516757
2 DARS2 NM_018122.5(DARS2):c.228-21_228-20delinsCindel Pathogenic 1057 rs1553201258 1:173797450-173797451 1:173828312-173828313
3 DARS2 NM_018122.5(DARS2):c.492+2T>CSNV Pathogenic 1062 rs142433332 1:173800770-173800770 1:173831632-173831632
4 PITX1 NM_002653.5(PITX1):c.388G>A (p.Glu130Lys)SNV Pathogenic 7505 rs121909109 5:134366980-134366980 5:135031290-135031290
5 RYR1 NM_000540.2(RYR1):c.7268T>A (p.Met2423Lys)SNV Pathogenic 12989 rs118192174 19:38990601-38990601 19:38499961-38499961
6 PITX1 NM_002653.5(PITX1):c.765_799del (p.Ala256fs)deletion Pathogenic 37253 rs730882191 5:134364615-134364649 5:135028925-135028959
7 CC2D2A NM_001080522.2(CC2D2A):c.4179+1deldeletion Pathogenic 56312 rs386833760 4:15589552-15589552 4:15587929-15587929
8 46;XY;t(2;10)(p25;q26)dnTranslocation Pathogenic 268018
9 PLOD2 NM_182943.3(PLOD2):c.2038C>T (p.Arg680Ter)SNV Pathogenic/Likely pathogenic 374012 rs780770356 3:145788912-145788912 3:146071125-146071125
10 KIAA1109 NM_015312.3(KIAA1109):c.1557T>A (p.Tyr519Ter)SNV Pathogenic/Likely pathogenic 183349 rs730882245 4:123128323-123128323 4:122207168-122207168
11 TRPV4 NM_021625.4(TRPV4):c.947G>A (p.Arg316His)SNV Pathogenic/Likely pathogenic 30473 rs387906905 12:110236624-110236624 12:109798819-109798819
12 INPP5E NM_019892.6(INPP5E):c.1132C>T (p.Arg378Cys)SNV Pathogenic/Likely pathogenic 400 rs121918130 9:139327634-139327634 9:136433182-136433182
13 TNFRSF13B NM_012452.2(TNFRSF13B):c.310T>C (p.Cys104Arg)SNV risk factor 5302 rs34557412 17:16852187-16852187 17:16948873-16948873
14 KAT6B NM_012330.4(KAT6B):c.5213C>T (p.Thr1738Ile)SNV Likely pathogenic 523500 rs1554846212 10:76789795-76789795 10:75030037-75030037
15 PLOD2 NM_182943.3(PLOD2):c.1361G>T (p.Gly454Val)SNV Likely pathogenic 374011 rs778360818 3:145797042-145797042 3:146079255-146079255
16 COL5A1 NM_001278074.1(COL5A1):c.2903del (p.Pro968fs)deletion Likely pathogenic 374067 rs1057518871 9:137690256-137690256 9:134798410-134798410
17 PKD1 NM_001009944.3(PKD1):c.7429C>T (p.Arg2477Cys)SNV Conflicting interpretations of pathogenicity 257000 rs376283361 16:2156459-2156459 16:2106458-2106458
18 VANGL1 NM_138959.3(VANGL1):c.523C>T (p.Arg175Trp)SNV Conflicting interpretations of pathogenicity 167818 rs142594314 1:116206600-116206600 1:115663979-115663979
19 46;X;idic(Y)(q11);t(2;6;12;3)(q24;q23;q12;p13)[21]/46;XY;t(2;6;12;3)dncomplex Uncertain significance 268021
20 PKD1 NM_001009944.3(PKD1):c.12014A>G (p.Gln4005Arg)SNV Uncertain significance 523352 rs760873748 16:2140799-2140799 16:2090798-2090798
21 AARS1 NM_001605.2(AARS1):c.2054T>C (p.Val685Ala)SNV Uncertain significance 523443 rs1555539904 16:70292059-70292059 16:70258156-70258156

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

73
# 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...

Cellular components 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 cilium GO:0005929 8.8 TRPV4 INPP5E CC2D2A

Molecular functions 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 calcium channel activity GO:0005262 8.62 TRPV4 RYR1

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
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
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50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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