Genetic epidemiology study of idiopathic talipes equinovarus

Abstract

Previous genetic studies of idiopathic talipes equinovarus (ITEV) suggest an environmental and genetic component to the etiology of ITEV. The present study was undertaken to assess the role of causal factors in the development of ITEV. A total of 285 propositi were ascertained, with detailed family history information available in 173 cases and medical records on the remaining 112 propositi. Information was collected on specific prenatal, parental, and demographic factors. No racial heterogeneity was noted among any of the factors. The overall ratio of affected males to females was 2.5:1. The incidence of twinning among all propositi was significantly increased (P=0.006) above the expected population frequency. A family history of ITEV was noted in 24.4% of all propositi studied. These findings, in addition to the detailed analysis of 53 pedigrees with ITEV history, suggest the potential role of a gene or genes operating in high-risk families to produce this foot deformity.

Update on Clubfoot: Etiology and Treatment

“…A recent study points toward a polygenic threshold model for clubfoot inheritance where multiple genes and environmental factors will be found to play a role [42]. Variants in genes responsible for a variety of environmental factors have been associated with an increase risk of clubfoot [31,39,44,59]. In addition, using a candidate gene approach, other genetic variants have been associated with clubfoot including variants in homeodomain transcription factors HOXD12 and HOXD13 [72], and several apoptotic genes including the caspase genes [32].…”

“…While it is becoming more clear that clubfoot is multifactorial in origin, genetic factors clearly play a role as suggested by the 33% concordance of identical twins and the fact that nearly 25% of all cases are familial [44]. Additional evidence for a genetic etiology is provided by differences in clubfoot prevalence across ethnic populations with the lowest prevalence in Chinese (0.39 cases per 1000 live births) and the highest in Hawaiians and Maoris (seven per 1000) [5,13].…”

“…Additional evidence for a genetic etiology is provided by differences in clubfoot prevalence across ethnic populations with the lowest prevalence in Chinese (0.39 cases per 1000 live births) and the highest in Hawaiians and Maoris (seven per 1000) [5,13]. Though the exact genetic mechanism of clubfoot has not yet been determined, a multifactorial and possibly polygenic causation has been suggested [44,75]. Earlier studies using complex segregation analyses suggested a single incompletely dominant disease gene with unmeasured factors contributing to incomplete penetrance [56,71].…”

“…In a study of over 3000 patients, Honein et al reported an association of smoking with clubfoot, with an adjusted odds ratio of clubfoot of 1.34 for smoking only, 6.52 for family history only, and 20.30 for combined exposure to smoking and family history [33]. Variants in genes responsible for the metabolism of tobacco [31], seasonal viral infections [44], elevated maternal homocysteine [39], and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms [59] have also been associated with an increased risk of clubfoot.…”

Pé torto congênito

“…[1][2][3][4][5] With approximate incidence of one in every 1,000 live births, it predominates in males, in the proportion of 2:1, with bilateral involvement in 50% of cases. [6][7][8][9] Population variations are found in relation to incidence, whereas in the Chinese, there are around 0.39 cases in every 1,000 live births, in Caucasians one to three cases per 1,000 live births, while in Hawaiians it occurs in about seven in every 1,000 live births. 6 …”