Talipes Equinovarus (Clubfoot)

GENESIS

Talipes equinovarus (TEV; clubfoot) is often a serious foot defect, but predicting severity and response to treatment in the newborn has been notoriously difficult. Over the past 25 years there has been a dramatic shift away from extensive surgical releases to manipulative methods with serial casting (primarily the Ponseti method), in which a series of manipulations and weekly casts are used to bring the foot into a corrected position, followed by the use of splinting and orthotics to maintain the corrected position. In general, the stiffer the foot, the more difficult it will be to correct by manipulation, but early treatment shortly after birth with manipulations and serial casting is extremely important, and relapse is strongly correlated with noncompliance with orthotic bracing. The term idiopathic talipes equinovarus is used to describe the most common type of isolated clubfoot that is not part of a syndrome. The birth prevalence varies among racial groups, averaging 1.12 per 1000 live births among Caucasians; it is lowest among Chinese (0.39 per 1000) and highest among Hawaiian and Maori people (6.8 per 1000). In a study of the birth prevalence of clubfoot in low- and middle-income countries, the birth prevalence ranged from 0.51 per 1000 in China, to 1.11 per 1000 in the Africa region, to 1.74 per 1000 in the Americas, to 1.21 per 1000 in Southeast Asia, to 1.21 per 1000 in India, to 1.19 per 1000 in the Eastern Mediterranean region, to 2.03 per 1000 in Turkey. Males are affected twice as often as females among all ethnic groups, and bilateral involvement occurs slightly more often than unilateral involvement, with the right side more frequently involved than the left side. Postural equinovarus occurs in 0.5 per 1000 live births and is two to three times more common among females than males. TEV can be either a positional deformation or a structural malformation resulting from a wide variety of causes (intrauterine compression, abnormal myogenesis, neurologic abnormalities, vascular insufficiency, and/or genetic factors).

Structural TEV can be either isolated or syndromic (termed complex TEV when there are associated malformations), and such syndromes can result from genetic, chromosomal, or teratogenic causes. Whenever TEV occurs as part of a broader pattern of altered morphogenesis, strong consideration should be given to various genetic connective tissue disorders and skeletal dysplasias that affect the tissues forming the foot (e.g., Larsen syndrome, diastrophic dysplasia, camptomelic dysplasia), neuromuscular disorders that result in diminished foot movement (e.g., spina bifida or distal arthrogryposis), and various types of vascular disruptions as possible causes. Isolated TEV is seen more frequently in large-for-gestational-age infants, as is congenital hip subluxation. TEV also occurs 3.1 times more frequently in infants born to obese diabetic women than in those born to nonobese, nondiabetic women. A population-based study of 6139 cases of clubfoot born in 10 US states from 2001 through 2005 reported strong associations between male sex, preterm birth, low birth weight, primiparity, and breech presentation, as well as dose-related associations with maternal smoking and both pregestational and gestational diabetes. A three-state case-control study of 677 cases of clubfoot revealed cases were more likely to be male and born to primiparous mothers and obese mothers. These associations were greatest in isolated and bilateral cases. Positive associations with high body mass index were confined to cases with a marker of fetal constraint (oligohydramnios, breech delivery, bicornuate uterus, plural birth), inheritance (family history in a first-degree relative), or vascular disruption (early amniocentesis, chorion villus sampling, plural gestation with fetal loss). It is not always possible to determine whether idiopathic TEV is caused by constraint-related foot deformations, and a multifactorial cause encompassing both environmental and genetic factors seems most likely. Positional TEV can result from uterine constraint owing to factors such as oligohydramnios, multiple gestation, or breech presentation ( Figs. 5.1 and 5.2 ).

TEV should be regarded as a multifactorial disorder resulting from a combination of genetic and environmental factors. TEV is positively associated with Hox family genes, collagen family genes, GLI3, N-acetylation genes, T-box family genes, apoptotic pathway genes, and muscle contractile family genes, as well as with maternal smoking. Among 785 individuals with TEV from the United Kingdom and The Netherlands, the male:female ratio was 2.3:1, 58% were affected bilaterally, and 11% had a first- to second-degree family history. One study of Pacific Island people noted a positive family history for idiopathic TEV in 24.4% of all patients studied, and in 20.8% pedigrees studied, parent-to-child transmission occurred. There is also evidence that the anterior tibial vascular tree is poorly developed in children with clubfoot, with a significantly greater prevalence of absence of the dorsalis pedis pulse in the parents of such children. Among 192 patients with 279 clubfeet, using vascular imaging the dorsalis pedis was most frequently reported as absent (21.5%) and the anterior tibial artery was most frequently reported as hypoplastic (18.3%), with 61% of patients noted to have a dominant supply from the posterior tibial artery. Therefore routine Doppler ultrasound (US) imaging is recommended prior to operative intervention. Parental smoking is a known risk factor for this multifactorial defect, and a family history of a first-degree relative with TEV, combined with maternal smoking, increases the risk for isolated TEV, thereby suggesting a gene/environment interaction. Oligohydramnios and early amnion rupture are associated with TEV, and there is a higher incidence of TEV with early amniocentesis at 11–12 weeks of gestation (1.3%) compared with second-trimester amniocentesis at 15–17 weeks (0.1%). This may relate to the relatively larger proportion of total amniotic fluid volume withdrawn for early amniocentesis (15.7% vs. 7.3% at mid-trimester) at a time when the fetal foot is assuming its normal position from a previous physiologic equinus position. This period may be unusually sensitive to constraint and/or vascular disruption. Amniotic fluid leakage before 22 weeks was the only significant factor associated with clubfoot, there being a 15% risk with leakage but only a 1.1% risk without leakage ( Fig. 5.3 ). No case of clubfoot had persistent leakage at 18–20 weeks. Such a transient fluid leak suggests that a disruptive process might have resulted in a developmental arrest of the foot as it moved from the normal equinus position at 9 weeks to the neutral position at 12 weeks. Vascular disruption may be a final common pathway for environmentally induced TEV, which has also been caused by maternal hyperthermia. The use of misoprostol, as well as other unsuccessful early pregnancy termination attempts that result in vascular disruption and hypoxic-ischemic insults to the spinal cord and brainstem, can result in structural TEV, arthrogryposis, Möbius sequence, and cranial nerve damage. Neuromuscular toxins administered during gestation or neuromuscular defects such as arthrogryposis, spinal muscular atrophy, meningomyelocele, and sacral dysgenesis are all associated with structural TEV.