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Incidence and prevalence of congenital clubfoot in Apulia: a regional model for future prospective national studies

Italian Journal of Pediatrics volume 49, Article number: 151 (2023) Cite this article

Abstract

Background

Congenital clubfoot is a fairly common and severe congenital malformation, most often of idiopathic origin. A smaller percentage of cases is related to chromosomal abnormalities and genetic syndromes. It is estimated that 0.5/1000 newborns are affected worldwide, with a male to female ratio of 2:1 and greater distribution in developing countries (80%). The “European Surveillance of Congenital Anomalies (EUROCAT)” reported clubfoot prevalence in European newborns, but data regarding Italy are missing or poor. We aim to provide detailed data on clubfoot incidence according to the Apulian Regional Registry on Congenital Malformations and to report current knowledge on clubfoot genetic factors.

Methods

We extrapolated data from the Regional Registry of Congenital Malformations to evaluate incidence and prevalence of congenital clubfoot in Apulia, Italy over a period of four years (2015–2018). We also performed a narrative review focusing on genetic mutations leading to congenital clubfoot.

Results

Over the period from 2015 to 2018 in Apulia, Italy, 124,017 births were recorded and 209 cases of clubfoot were found, accounting for an incidence rate of 1.7/1,000 and a prevalence rate of 1.6/1,000. Six families of genes have been reported to have an etiopathogenetic role on congenital clubfoot.

Conclusions

Incidence and prevalence of congenital clubfoot in Apulia, Italy, are comparable with those reported in the other Italian regions but higher than those reported in previous studies from Europe. Genetic studies to better classify congenital clubfoot in either syndromic or isolated forms are desirable.

Introduction

Congenital clubfoot, also known as talipes equinovarus, is a fairly common and severe congenital malformation, featuring structural defects of the tissues of the foot and lower leg that are responsible for the abnormal positioning of the foot and ankle joints [1]. If left untreated, severe disability and deformities are expected [2]. The etiology of congenital clubfoot is still unknown. To date, the hypothesis of a multifactorial origin is the most widely accepted, since both genetic and environmental factors (i.e. smoke during pregnancy) have an etiopathogenetic role [3].

Eighty percent of cases are idiopathic isolated congenital defects [4], whereas 20% are related to chromosomal abnormalities and genetic syndromes, such as distal arthrogryposis (DA) and myelomeningocele [5].

In about 25% of isolated forms of clubfoot, a positive family history is found, confirming the role of genetic factors [6]. Besides, a higher incidence in monozygotic twins (33%) compared to dizygotic twins (3%) has been described and a 30% risk of heritability of isolated clubfoot has been recently reported [7]. Monochorionic triplets with bilateral isolated clubfoot have also been described [3].

Since the clinical presentation of isolated and syndromic forms may be overlapping, genetic studies in patients with syndromic forms could provide insights on the cause of underlying isolated clubfoot [3].

To describe how often a disease or another health event occurs in a population, different measures of disease frequency can be used. The prevalence reflects the number of existing cases of a disease and can be seen as a measure of disease status: it is the proportion of people in a population having a disease. In contrast to the prevalence, the incidence reflects the number of new cases of disease and can be reported as a risk or an incidence rate. The incidence rate can be calculated by dividing the number of subjects developing a disease by the total time at risk for all people to get the disease. The denominator of this formula includes a measure of time instead of just a number of subjects. The risk is the probability that a subject within a population will develop a given disease, or other health outcome, over a specified follow-up period. It can be calculated by dividing the number of subjects developing the disease over a certain period by the total number of subjects followed over that period.

It is estimated that 0.5/1000 newborns are affected worldwide (150,000–200,000 newborns per year and 7–43 cases of clubfoot/year/million population), with a male to female ratio of 2:1 and greater distribution in developing countries (80%). Kruse and colleagues suggested a reason for this gender difference in the Carter effect [8]. In 50% of cases, it affects both feet; in unilateral clubfoot, the right side is more often involved [9]. According to some epidemiological investigations, major differences in prevalence have been identified between ethnic groups, reaching the highest rates in Maori (7/1000 newborns) [10], Polynesians and Hawaiians (6.8/1000 newborns) [11], and southern Africans (3.5/1000 newborns) [12]. Conversely, the percentages in the Chinese (0.39/1000 newborns) 2, Japanese (0.87/1000 newborns) [13], Asian (0.57/1000 newborns), European (1.2/1000 newborns) [14], and Brazilian population (1.7/1000 newborns) [14] are lower. Recently, the “European Surveillance of Congenital Anomalies (EUROCAT)” reported clubfoot prevalence in European newborns [15], but data regarding Italy are missing or poor, including only the regions of Tuscany and Emilia Romagna [16].

In the latest Italian regional report, Pavone and coll. reported 827 cases of isolated congenital talipes equinovarus (ICTEV) out of 801,324 live births in the Sicilian population from 1991 to 2004, with a prevalence of nearly 1:1000, a male to female ratio of 2:1, and the right foot affected slightly more frequently than the left [17]. In Italy an accurate estimate of regional incidence of congenital clubfoot is possible from The “Certificate of Delivery Care Registry (CeDAP)”, which is a web system providing epidemiological and sociodemographic information about newborns. The current data collection of the CeDAP started on 1 January 2002, following the ministerial Decree no. 349 of 16 July 2001. The certificate is structured into six sections; each section collects specific information regarding birthplace, parents, pregnancy, childbirth, newborns, congenital malformations or the causes of neonatal death. In case of dead-births or fetal malformations, specific information is collected in the certificate. The certificate is completed within the tenth day after birth by the midwife or the doctor in charge.

Aim of the study

To provide detailed data on clubfoot incidence according to the Apulian Regional Registry on Congenital Malformations and to report current knowledge on clubfoot genetic factors.

Materials and methods

The Apulian Regional Registry of Congenital Malformations was established on 3rd September 2013 to collect data on congenital malformations, diagnosed either prenatally or by the end of the first year of life. It is regularly updated by healthcare providers across the entire regional territory, hence it provides accurate data on prevalence, incidence and variation across time and space of congenital malformations.

We extrapolated data from the Regional Registry of Congenital Malformations to evaluate incidence and prevalence of congenital clubfoot in Apulia, Italy over a period of four years (2015–2018).

Data were also sorted according to the six Apulian provinces of Brindisi, Taranto, BAT (Barletta-Andria-Trani), Bari, Foggia, and Lecce. Incidence and prevalence were expressed as the new or the total cases of clubfoot per annual births, respectively. Incidence rate was expressed as the number of new subjects diagnosed with clubfoot per year per 1,000 births. Prevalence rate was expressed as the total number of subjects diagnosed with clubfoot per year per 1,000 births.

We also performed a narrative review focusing on genetic mutations leading to congenital clubfoot. An exhaustive search for eligible studies was performed in PubMed, Embase, Medline, Cochrane library and Web of Science databases.

The search string used was “(clubfoot [MeSH term] OR congenital talipes equinovarus[All fields] OR clubfeet [MeSH term]) AND (gene* OR genetic association)”.

Additional studies were sought using references in articles retrieved from searches. Search limits were set for studies published between 1st January 1998 and 29th April 2022 in English language.

Results

Over the period from 2015 to 2018 in Apulia, Italy, 124,017 births were recorded and 209 cases of clubfoot were found, accounting for an incidence rate of 1.7/1,000 and a prevalence rate of 1.6/1,000. Based on collected data, the highest incidence of congenital clubfoot (1.9/1,000) occurred in 2016 (60 cases/31,681 births) and 2018 (56 cases/29,399 births). The lowest incidence rate (1.4/1,000) was observed in 2014 (43 cases/32,161 births) (Table 1).

Table 1 Incidence and prevalence rate (n/1,000 births) of congenital clubfoot in Apulia, from 2015 to 2018
Full size table
Table 2 Incidence rate of congenital clubfoot (n/1,000 births) in Apulia, sorted by the six provinces
Full size table

Over the studied period, Foggia, BAT (Andria-Barletta-Trani), Bari, and Lecce recorded an increase in the incidence of clubfoot, whereas a decrease was seen in Brindisi and Taranto (Table 2). The trend of the annual prevalence of congenital clubfoot from 2015 to 2018 in the six Apulian provinces is displayed in Fig. 1.

Fig. 1
figure 1

Annual prevalence rate of congenital clubfoot in the six Apulian provinces

Full size image

Narrative review

Six families of genes have been reported to have an etiopathogenetic role on congenital clubfoot.

PITX1-TBX4 pathway and Homeobox (HOX) genes

The strongest evidence for the role of genetics regards the PITX1-TBX4 pathway, needed for normal hindlimb development [18, 19]. The PITX1 gene is responsible for rapid changes in pelvic morphology in lower vertebrates and it is involved in foot morphogenesis, being expressed almost exclusively in the hindlimb. In isolated clubfoot phenotypes, dominant segregating mutation in PITX1 [20], inherited microduplications of TBX [4, 21,22,23,24] and copy number variants [25] have been described.

In addition to PITX1-TBX4, the involvement of Homeobox (HOX) genes has also been reported. The HOX genes encompass four groups of genes (HOXA-D) controlling limb development throughout the axial and appendicular skeleton [26]. HOXD12 and HOXD13 single nucleotide polymorphisms (SNPs) have been associated with idiopathic clubfoot [27].

Recently, HOXC microdeletions have been shown to overlap with a noncoding region upstream of HOXC13. A missense SNP in HOXC11 in a family with an isolated form of clubfoot and a missense SNP in HOXC12 in clubfoot patients have been reported [28]. The role of insulin-like growth factor binding protein (IGFBP3), HOXD13 gene and genes regulating caspase activity have also been evaluated [3].

FSTL gene

FSTL5 is a gene involved in embryonic and postnatal development and it is also a modulator of transforming growth factor beta and bone morphogenetic protein signaling [29].

Studies in mice have shown that FSTL5 is expressed in cartilage cells during later stages of embryonic hind limb development but its abnormalities do not correlate with overt clubfoot-like deformity. This suggests that in the pathogenesis of idiopathic talipes equinovarus, FSTL5 mutations affect other cell lines such as neural cells.

SHOX gene duplication

The SHOX gene is part of a large family of homeobox genes, which act during early embryonic development to control the formation of body structures being essential for the growth and maturation of long bones.

One copy of the SHOX gene is located on each sex chromosome in the pseudo-autosomal region. Microduplications of the pseudo-autosomal chromosome region Xp22.33 (Par1) containing SHOX have been found in about 1% of clubfoot patients [30].

PMA mice

The PMA (peroneal muscular atrophy) mouse is a good animal model for disorders like arthrogryposis multiplex congenita or congenital clubfoot deformity.

In PMA mice, the peroneal branches of the sciatic nerves are absent. The defect is related to reduced growth of sciatic nerve lateral motor column (LMC) neurons and to an upregulation of LIM-domain kinase 1 (Limk1).

Genetic analyses showed that the mutation acts in the EphA4–Limk1–Cfl1/cofilin–actin pathway [31].

Muscle contractile genes

Alterations in muscle fibers and a growth disorder with a disproportionate amount of type I fibers in the posterior and medial muscle groups were found, suggesting the presence of an abnormality in neural development. Involvement of the tendon sheaths of the finger flexors and posterior tibial tendons can also be found, which shows signs of cellular hypoplasia with smaller cells and less cytoplasmic volume. [9]

Newborns with idiopathic talipes equinovarus show calf muscle hypoplasia at birth, suggesting the involvement of genes related to muscle development. Accordingly, alterations of genes encoding for muscle proteins (MYH3, TPM2, TNNT3, TNNI2, and MYH8) cause congenital contractures. Other genes involved are those encoding myosin heavy chains 3 and 8 (MYH3, MYH8), troponin I and T (TNNI2, TNNT3), and tropomyosin (TPM2). [32]

FLNB and ECM proteins

Filamin B (FLNB) is a protein that binds actin in a dynamic structure. FLNB missense mutations have been associated with isolated clubfoot.

Genetic analyses revealed mutations in genes involved in various cellular processes, including proliferation, apoptosis, differentiation, and extracellular matrix formation and remodeling. Genes in the collagen family have also been linked to idiopathic congenital talipes equinovarus. Mutations in genes encoding the ECM proteins COL9A1, COL9A2, COL9A3, COMP and MATN3, as well as the transmembrane glycoprotein involved in matrix organization, SLC26A2, have been associated with clubfoot. Mutations in peroxisomal biogenesis (PEX) factors, including PEX26, are also included in the pathogenesis of clubfoot [33].

Discussion

The present study is based on a retrospective study focusing on the Italian pediatric population affected by clubfoot of a single Italian region (Apulia), where a Regional registry has been instituted in 2013, since to date national data from a national registry are still lacking [34].

According to CeDAP certificates, the incidence rate of congenital clubfoot varies significantly across Italian regions, ranging from 2.8/1,000 (Liguria) to 23.4/1,000 (Valle d’Aosta) [34].

We report a prevalence rate of 1.6/1,000 and an incidence rate of 1.7/1,000 for congenital clubfoot over the period from 2015 to 2018 in Apulia.

A similar prevalence rate was reported from the registries of Umbria and Abruzzo, while the lowest prevalence rate are reported from Campania (0.1/1,000) and Sardinia (0.4/1,000).

Only few studies on the prevalence of clubfoot have been carried out worldwide.

A European study was conducted using data from the EUROCAT network from 1995 to 2011. The total prevalence of congenital clubfoot was 1.13/1,000 births (95% CI 1.10–1.16). The prevalence of congenital clubfoot without chromosomal abnormalities was 1.08/1,000 births (95% CI 1.05–1.11), and the prevalence of isolated congenital clubfoot was 0.92/1,000 births (95% CI 0.90–0.95). However, significant geographical differences in prevalence emerge in this study: from 0.44/1,000 births in Tuscany and 0.45/1,000 births in the Basque Country to 1.68/1,000 births in Wales. A decreasing trend over time was observed for both incidence and prevalence. The majority of cases were isolated congenital clubfoot (82%), whereas 11% had associated major congenital anomalies. The prenatal detection of isolated congenital clubfoot rate increased over time, reaching a peak of 22% [35].

The overall prevalence of congenital clubfoot in EUROCAT study was comparable with those observed in other studies: 1.8/1,000 livebirths for all congenital clubfoot cases and 1.1/1,000 births for isolated congenital clubfoot in a study in Southern Australia [36] and 1.14/1,000 livebirths for isolated congenital clubfoot in Iowa [35, 37].

In a different study based on The National Swedish register, Sweden reported 828 isolated clubfeet and 77 non-isolated clubfeet from 2016 to 2019. The prevalence rate was 1.24/1,000 live births for isolated clubfoot, and 0.11/1,000 for non-isolated cases. In total 612 children with isolated or non-isolated clubfoot were recorded, accounting for a prevalence rate of 1.35/1,000. [38]

From 2012 to 2015 a retrospective descriptive study based on the Sri Lanka Clubfoot Program database reported 87% idiopathic clubfoot, 48% bilateral deformities and 13% non-isolated clubfoot. [39]

An accurate estimate of incidence and prevalence is essential not only for epidemiological-statistical purposes but also to improve genetic diagnostic panels. Unfortunately, our data lack the distinction in isolated or syndromic forms. Moreover, available literature on the etiology of clubfoot has important limitations due to considerable heterogeneity. To date, there is no consensus on which genetic abnormality should be regarded as the main causative target. Besides the PITX1-TBX4 pathway and Homeobox (HOX) genes, whose role is historically recognized, neural cell line mutations (e.g. FSTL gene), SHOX gene and abnormalities in cellular matrix cells, muscle fibers proteins and peroxisomes deserve some importance. However, further international collaborative studies are strongly encouraged to gain a deeper knowledge on genetic causative factors and provide genetic diagnostic panels.

Strenghts and limitations

The present study provides accurate and reliable data from an Italian region and poses the basis for a larger work aimed to estimate the national extent of this pathology. Limitations are given by the retrospective nature of the study, the narrow time frame considered (2015–2018), and the lack of distinction in isolated or syndromic forms of congenital clubfoot.

Conclusions

Congenital clubfoot is an emerging malformation whose incidence and prevalence in Apulia, Italy, range from 1.4 to 1.9 and 1.3 to 1.9 per 1,000 births, respectively. Such values are comparable with Italian data from the CeDAP registry but higher than those reported in previous studies from Europe. An accurate prospective national study is warranted to improve the knowledge on incidence and prevalence on a larger scale. Genetic studies to better classify congenital clubfoot in either syndromic or isolated forms are also desirable.

Data Availability

All relevant data are included in the article.

Abbreviations

CeDAP:

Certificate of Delivery Care Registry

DA:

Distal arthrogryposis

EUROCAT:

European Surveillance of Congenital Anomalies

FLNB:

Filamin B

HOX:

Homeobox

ICTEV:

Isolated congenital talipes equinovarus

LMC:

Lateral motor column

PEX:

Peroxisomal

PMA:

Peroneal muscular atrophy

References

  1. Basit S, Khoshhal KI. Genetics of clubfoot; recent progress and future perspectives. Eur J Med Genet. 2018;61:107–13.

    Article  PubMed  Google Scholar 

  2. O’Shea RM, Sabatini CS. What is new in idiopathic clubfoot? Curr Rev Musculoskelet Med. 2016;9:470–7.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sadler B, Gurnett CA, Dobbs MB. The genetics of isolated and syndromic clubfoot. J Child Orthop. 2019;13(3):238–44. https://doi.org/10.1302/1863-2548.13.190063. PMID: 31312262; PMCID: PMC6598048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wynne-Davies R. Family studies and the cause of congenital club foot. Talipes equinovarus, talipes calcaneo-valgus and metatarsus varus. J Bone Joint Surg [Br]. 1964;46–B:445–63.

    Article  Google Scholar 

  5. Gurnett CA, Boehm S, Connolly A, Reimschisel T, Dobbs MB. Impact of congenital talipes equinovarus etiology on treatment outcomes. Dev Med Child Neurol. 2008;50:498–502.

    Article  PubMed  Google Scholar 

  6. Lochmiller C, Johnston D, Scott A, Risman M, Hecht JT. Genetic epidemiology study of idiopathic talipes equinovarus. Am J Med Genet. 1998;79:90–6.

    Article  CAS  PubMed  Google Scholar 

  7. Engell V, Nielsen J, Damborg F, et al. Heritability of clubfoot: a twin study. J Child Orthop. 2014;8:37–41.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kruse LM, Dobbs MB, Gurnett CA. Polygenic threshold model with sex dimorphism in clubfoot inheritance: the Carter effect. J Bone Jt Surg Am 2008.

  9. Gunalan R, Mazelan A, Lee Y, Saw A. Pattern of presentation and outcome of short-term treatment for idiopathic clubfoot / CTEV with Ponseti Method. Malays Orthop J 2016.

  10. Beals RK. Club foot in the Maori: a genetic study of 50 kindreds. N Z Med J 1978.

  11. Chung CS, Nemechek RW, Larsen IJ, Ching GH. Genetic and epidemiological studies of clubfoot in Hawaii. General and medical considerations. Hum Hered 1969.

  12. van Pompe HF. Congenital musculoskeletal malformation in South African blacks: a study of incidence. S Afr Med J 1976.

  13. Yamamoto H. A clinical, genetic and epidemiologic study of congenital club foot. Jinrui Idengaku Zasshi 1979.

  14. Faldini C, Traina F, Nanni M, Sanzarello I, Borghi R, Perna F. Congenital idiopathic talipes equinovarus before and after walking age: observations and strategy of treatment from a series of 88 cases. J Orthop Traumatol. 2016;17:81–7. https://doi.org/10.1007/s10195-015-0377-4.

    Article  PubMed  Google Scholar 

  15. Ficara A, Syngelaki A, Hammami A, Akolekar R, Nicolaides KH. Value of routine ultrasound examination at 35–37 weeks’ gestation in diagnosis of fetal abnormalities. Ultrasound Obstet Gynecol. 2020;55:75–80. https://doi.org/10.1002/uog.20857.

    Article  CAS  PubMed  Google Scholar 

  16. Farr A, Wachutka E, Bettelheim D, Windsperger K, Farr S. Perinatal outcomes of infants with congenital limb malformations: an observational study from a tertiary referral center in Central Europe. BMC Pregnancy Childbirth. 2020;20:35. https://doi.org/10.1186/s12884-020-2720-x.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Nemec U, Nemec SF, Kasprian G, Brugger PC, Bettelheim D, Wadhawan I, Kolb A, Graham JM, Rimoin DL, Prayer D. Clubfeet and associated abnormalities on fetal magnetic resonance imaging. Prenat Diagn. 2012;32:822–8. https://doi.org/10.1002/pd.3911.

    Article  PubMed  Google Scholar 

  18. Hasson P, DeLaurier A, Bennett M, et al. Tbx4 and tbx5 acting in connective tissue are required for limb muscle and tendon patterning. Dev Cell. 2010;18:148–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Logan M, Tabin CJ. Role of Pitx1 upstream of Tbx4 in specification of hindlimb identity. Science. 1999;283:1736–9.

    Article  CAS  PubMed  Google Scholar 

  20. Gurnett CA, Alaee F, Kruse LM, et al. Asymmetric lower-limb malformations in individuals with homeobox PITX1 gene mutation. Am J Hum Genet. 2008;83:616–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Alvarado DM, Aferol H, McCall K, et al. Familial isolated clubfoot is associated with recurrent chromosome 17q23.1q23.2 microduplications containing TBX4. Am J Hum Genet. 2010;87:154–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lu W, Bacino CA, Richards BS, et al. Studies of TBX4 and chromosome 17q23.1q23.2: an uncommon cause of nonsyndromic clubfoot. Am J Med Genet A. 2012;158:1620–7.

    Article  CAS  Google Scholar 

  23. Peterson JF, Ghaloul-Gonzalez L, Madan-Khetarpal S, et al. Familial microduplication of 17q23.1–q23.2 involving TBX4 is associated with congenital clubfoot and reduced penetrance in females. Am J Med Genet A. 2014;164:364–9.

    Article  CAS  Google Scholar 

  24. Alvarado DM, McCall K, Aferol H, et al. Pitx1 haploinsufficiency causes clubfoot in humans and a clubfoot-like phenotype in mice. Hum Mol Genet. 2011;20:3943–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Alvarado DM, Buchan JG, Frick SL, et al. Copy number analysis of 413 isolated talipes equinovarus patients suggests role for transcriptional regulators of early limb development. Eur J Hum Genet. 2013;21:373–80.

    Article  CAS  PubMed  Google Scholar 

  26. Pineault KM, Wellik DM. Hox genes and limb musculoskeletal development. Curr Osteoporos Rep. 2014;12:420–7.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Wang LL, Fu WN, Li-Ling J, et al. HOXD13 may play a role in idiopathic congenital clubfoot by regulating the expression of FHL1. Cytogenet Genome Res. 2008;121:189–95.

    Article  CAS  PubMed  Google Scholar 

  28. Alvarado DM, McCall K, Hecht JT, Dobbs MB, Gurnett CA. Deletions of 5¢ HOXC genes are associated with lower extremity malformations, including clubfoot and vertical talus. J Med Genet. 2016;53:250–5.

    Article  CAS  PubMed  Google Scholar 

  29. Anas M, Khanshour YH, Kidane J, Kozlitina R, Cornelia A, Rafipay V, De Mello M, Weston N, Paria A, Khalid JT, Hecht MB, Dobbs BS, Richards N, Vargesson FK, Hamra M, Wilson C, Wise, Christina A, Gurnett, Jonathan J. Rios, genetic association and characterization of FSTL5 in isolated clubfoot. Hum Mol Genet. November 2020;29:15. https://doi.org/10.1093/hmg/ddaa236.

  30. Sadler B, Haller G, Antunes L, Nikolov M, Amarillo I, Coe B, Dobbs MB, Gurnett CA, Rare. and de novo duplications containing SHOX in clubfoot. J Med Genet. 2020;57(12):851–857. https://doi.org/10.1136/jmedgenet-2020-106842. Epub 2020 Jun 9. PMID: 32518174; PMCID: PMC7688552.

  31. Collinson JM, Lindström NO, Neves C, Wallace K, Meharg C, Charles RH, Ross ZK, Fraser AM, Mbogo I, Oras K, Nakamoto M, Barker S, Duce S, Miedzybrodzka Z, Vargesson N. The developmental and genetic basis of ‘clubfoot’ in the peroneal muscular atrophy mutant mouse. Development. 2018;145(3):dev160093. https://doi.org/10.1242/dev.160093. PMID: 29439133; PMCID: PMC5818009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Weymouth KS, Blanton SH, Bamshad MJ, Beck AE, Alvarez C, Richards S, Gurnett CA, Dobbs MB, Barnes D, Mitchell LE, Hecht JT. Variants in genes that encode muscle contractile proteins influence risk for isolated clubfoot. Am J Med Genet A. 2011;155A(9):2170–9. https://doi.org/10.1002/ajmg.a.34167. Epub 2011 Aug 10. PMID: 21834041; PMCID: PMC3158831.

    Article  CAS  PubMed  Google Scholar 

  33. Pavone V, Chisari E, Vescio A, Lucenti L, Sessa G, Testa G. The etiology of idiopathic congenital talipes equinovarus: a systematic review. J Orthop Surg Res. 2018;13(1):206. https://doi.org/10.1186/s13018-018-0913-z. PMID: 30134936; PMCID: PMC6104023.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Dibello D, Torelli L, Di Carlo V, d’Adamo AP, Faletra F, Mangogna A, Colin G. Incidence of congenital clubfoot: Preliminary Data from Italian CeDAP Registry. Int J Environ Res Public Health. 2022;19(9):5406. https://doi.org/10.3390/ijerph19095406. PMID: 35564801; PMCID: PMC9105829.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Wang H, Barisic I, Loane M, Addor MC, Bailey LM, Gatt M, Klungsoyr K, Mokoroa O, Nelen V, Neville AJ, O’Mahony M, Pierini A, Rissmann A, Verellen-Dumoulin C, de Walle HEK, Wiesel A, de Wisniewska K, den Berg LTW, Dolk H, Khoshnood B, Garne E. Congenital clubfoot in Europe: a population-based study. Am J Med Genet A. 2019;179(4):595–601. Epub 2019 Feb 10. PMID: 30740879.

    Article  CAS  PubMed  Google Scholar 

  36. Byron-Scott, R., Sharpe, P., Hasler, C., Cundy, P., Hirte, C., Chan, A., … Haan, E.(2005). A south Australian population-based study of congeni- tal talipes equinovarus.Paediatric and Perinatal Epidemiology, 19(3), 227–237.

  37. Kancherla V, Romitti PA, Caspers KM, Puzhankara S, Morcuende JA. Epidemiology of congenital idiopathic talipes equinovarus in Iowa, 1997–2005. Am J Med Genet: A. 2010;152A(7):1695–700.

    Article  PubMed  Google Scholar 

  38. Esbjörnsson AC, Johansson A, Andriesse H, Wallander H. Epidemiology of clubfoot in Sweden from 2016 to 2019: a national register study. PLoS ONE. 2021;16(12):e0260336. https://doi.org/10.1371/journal.pone.0260336. Published 2021 Dec 2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wijayasinghe SR, Abeysekera WYM, Dharmaratne TSS. Descriptive Epidemiology of Congenital Clubfoot Deformity in Sri Lanka. J Coll Physicians Surg Pak. 2018;28(2):166–168. https://doi.org/10.29271/jcpsp.2018.02.166. PMID: 29394982.

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Authors and Affiliations

  1. Neonatology and Neonatal Intensive Care Unit (NICU), University of Bari Aldo Moro, Bari, Italy

    Raffaella Panza & Nicola Laforgia

  2. Orthopaedics Unit, Department of Basic Medical Science, Neuroscience and Sensory Organs, School of Medicine, University of Bari Aldo Moro, Bari, Italy

    Federica Albano, Alberto Casto & Cosimo Del Vecchio

  3. Department of Interdisciplinary Medicine, University of Bari Aldo Moro, Bari, Italy

    Nicola Laforgia

  4. Unit of Pediatric Orthopaedics and Traumatology, Giovanni XXIII Children’s Hospital, Via Giovanni Amendola, Bari, 70126, Italy

    Daniela Dibello

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Contributions

Conceptualization, D.D. and N.L.; Methodology, R.P. and C.D.V.; Writing – Original Draft Preparation, R.P. and F.A.; Writing – Review & Editing, R.P., F.A., and A.C.; Supervision, D.D. and N.L. All authors read and approved the final manuscript.

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Correspondence to Nicola Laforgia.

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Panza, R., Albano, F., Casto, A. et al. Incidence and prevalence of congenital clubfoot in Apulia: a regional model for future prospective national studies. Ital J Pediatr 49, 151 (2023). https://doi.org/10.1186/s13052-023-01559-9

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Italian Journal of Pediatrics

ISSN: 1824-7288

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