Introduction: Between 1 and 4 per 1000 births worldwide are affected by clubfoot. Clubfoot etiology is unclear, but both genetic and environmental factors are thought to be involved. Low folate status in pregnant women has been implicated in several congenital malformations and folate metabolism may be affected by polymorphisms in the MTHFR gene.

Methods: Using a case-parent triad design, we investigated whether the MTHFR C677T polymorphism, and maternal peri-conceptional folic acid supplement use, influenced risk of isolated clubfoot. 375 case-parent triads took part.

Results: Among children there was a significant trend of decreasing clubfoot risk with increasing number of Talleles: relative risk (RR ) CT vs CC=0.75 (95% CI: 0.57,0.97); RR TT vs CC=0.57 (95% CI: 0.37,0.91); p trend=0.006. This association was not modified by maternal folic acid use.

Conclusion: Maternal MTHFR genotype did not influence risk of clubfoot in the offspring overall, although a possible interaction with folic acid use was found. This is the first report of a specific genetic polymorphism associated with clubfoot. The direction of the association is intriguing and suggests DNA synthesis may be relevant in clubfoot development. However, clubfoot mechanisms are poorly understood and the folate metabolism pathway is complex. Further research is needed to elucidate these relationships.

Background: Congenital talipes equinovarus (CTEV) is a common developmental disorder of the foot, affecting between 1 and 4.5 babies per 1000 live births. The etiology is not well elucidated. While both genetic and environmental factors are implicated, no specific genes have been identified and little is known about environmental risk factors.

Methods: We conducted a case-control study of idiopathic congenital talipes equinovarus (ICTEV) in the United Kingdom. 194 cases and 60 controls were recruited. Pedigrees were obtained for 162 cases.

Results: The rank of the index pregnancy, maternal education and cesarean delivery were significantly associated with ICTEV risk in a multivariate model. There were suggestions that maternal use of folic acid supplements in the three months before the pregnancy decreased ICTEV risk, and that parental smoking during the pregnancy increased risk. One quarter of pedigrees showed a family history of CTEV, and autosomal dominant inheritance was suggested in some of these.

Conclusion: Uterine restriction did not appear to have a strong influence on ICTEV development in our study. Large population-based studies are needed to clarify the etiology of this common developmental disorder.

Introduction and Aims: To illustrate complete, single chance correction, of congenital clubfoot in 89 cases in the Pacific Islands, from a humanitarian, scientific, and surgical perspective. To identify the unique Polynesian clubfoot gene, its particular characteristics, and the environmental factor suspected to trigger its activation.

Method: A rolling surgical procedure commencing with Turco operation and progressing as far as lateral border decancellation, is used. Tripple arthrodesis is not done, obsessive and meticulous after care is required for two weeks.

Results: Return clinic visits through inter-islands hospitals, aid post and villages, have revealed excellent long-term corrections. There have been no reoccurences and the surgical team have received no negative feedback.

Genetic studies suggest a single dominant gene of variable penetrants. Seventeen comfirmed perterdries from Vanawatu indicate a recessive inheritance in the population. The frequency varies from Island to Island, eg. Efate 0.26, Tanna 0.13. Seven cases gave a history of at least one other family member being affected. However, there was no vertical transmission in any degrees we conclude in a recessive mode of inheritance for ITEV in South Pacific Polynesian people. The desired surgical protocol is determined by an incremental combination of current surgical procedures with careful placement of incisions. Associated bone procedures are carefully selected. A rigorous and disciplined post-operative protocol has avoided known complications to date.

Conclusion: Single stage ITEV correction in adverse surgical conditions is successful and straightforward. The recipient is given a chance to avoid life-long degradation.

Genetic studies indicate a simple environmental cause activating a single dominant gene with 33% penetrants.