Clubfoot

Clubfoot is a multiplanar deformity resulting in the fetal foot fixed in adduction, supination, varus or valgus position, and is characterized by a subluxation of the talo-calcaneo-navicular joint, with underdevelopment of the soft tissues on the medial side of the foot, and frequently of the calf, and peroneal muscles (1).

Talipes equinovarus.

LB98.

Clubfoot is one of the most common congenital anomalies detected prenatally with a prevalence ranging from 1/1000 to 3/1000 live births (2).

It is bilateral in about 50% of cases, with a higher incidence in males compared to females (3).

Clubfoot may be considered as congenital, syndromic, or positional. Congenital clubfoot presents commonly as an isolated anomaly affecting bones, muscles, tendons, and blood vessels of one or both feet in an otherwise structurally normal fetus. Conversely, syndromic or complex cases are associated with additional structural chromosomal anomalies. Positional clubfoot results from a persistently abnormal (adducted/abducted) foot position in a restrictive uterine environment.

The precise etiology of isolated clubfoot has not been completely elucidated yet. Isolated clubfoot has been shown to be the result of a polygenetic inheritance, as also confirmed by the elevated prevalence in some populations and the male-to-female ratio of 2:1 (4-6). Complex clubfoot presents in the setting of chromosomal, mainly Trisomy 18, or genetic syndromes, especially those involving the neuromuscular system such as arthrogryposes (7-12). On the other hand, mechanical factors such as breech presentation, oligohydramnios, uterine anomalies and amniotic bands are the most commonly reported responsible factors of positional clubfoot (4,6).

Associated anomalies are common in fetuses with clubfeet. The risk of associated anomalies is higher in clubfeet presenting in the setting of a chromosomal or genetic disorder. In fetuses with apparently isolated clubfeet on ultrasound the incidence of associated anomalies on follow-up scan is about 8%, while 7% of cases labelled as isolated clubfeet prenatally show associated anomaly at birth (13-15).

The most common neuromuscular condition found at birth and not detected at prenatal ultrasound was arthrogryposis. Arthrogryposis encompasses a heterogeneous group of conditions characterized by multiple joint contractures due to central nervous system disorders. Prenatal diagnosis of arthrogryposis is commonly reached in the second and third trimester of pregnancy and is based upon the visualization of multiple joints contractures, lack of fetal movements and polyhydramnios. Therefore, serial, longitudinal ultrasound assessments throughout pregnancy are needed in order to rule out that talipes are the first sign of a general neuromuscular disorder.

Other anomalies associated with clubfeet involve musculoskeletal, cardiac, urinary and gastrointestinal systems. When looking at syndromic clubfoot, the majority of cases are associated to sex chromosomal anomalies, such as Klinefelter syndrome, while the incidence of trisomy is generally negligible (14,16-18).

Clubfoot is a multifactorial disorder with an etiopathology still unclear, but a genetic contribution in case of isolated clubfoot is plausible as 24.4% of patients with isolated clubfoot had a family history of clubfoot (2). Moreover, chromosomal micro-array (CMA) analyses showed that recurrent copy number variants involving a transcriptional target of PITX1 were found in about 5% of all patients with familial isolated clubfoot (19).

Clubfoot can be diagnosed on ultrasound from the early first trimester of pregnancy when the plantar surface of the fetal foot is persistently seen in the same sagittal plane as both lower extremity bones (i.e., tibia and fibula) throughout the entire examination, both on transverse and longitudinal view (20-23).

Prenatal counselling should focus on risk of aneuploidy, association with genetic syndrome, short- and long-term prognosis. 

The first issue in the prenatal management of clubfoot is a close ultrasound surveillance throughout pregnancy to rule out associated structural anomalies, which can significantly impact short and long-term prognosis. Detailed fetal neurosonography and echocardiography are also warranted in view of the association with cerebral and cardiac anomalies.

There is no consensus yet also on whether invasive tests should be offered in cases of clubfoot, as the incidence of karyotype abnormalities varies in the literature, particularly when there are no ultrasound signs suggestive of additional anomalies. Conversely, prenatal invasive testing should be recommended when other associated risk factors for aneuploidy, such as advanced maternal age or abnormal first trimester screening test results, co-exist with clubfoot. CMA has been recently introduced in routine genetic analysis and it is recommended in fetuses undergoing invasive procedures for major structural anomalies detected on ultrasound (24). Never the less, it is still not possible to extrapolate a robust evidence on the role of CMA analysis in fetuses presenting with clubfoot on ultrasound, as the majority of previously published studies includes only very few cases evaluating the role of CMA in cases of prenatal diagnosis of isolated talipes (13).

Fetal magnetic resonance imaging (MRI) has been shown to provide additional information compared to ultrasound in fetuses affected by central nervous system anomalies. However, its role in fetal anomalies not involving the brain is less clear, and currently there is no evidence to support the routine use of fetal MRI in fetuses with clubfoot, unless there is a suspicion of associated cerebral anomaly on ultrasound.

Prognosis of syndromic clubfoot is closely related to the presence of associated anomalies.

Fetuses with prenatal diagnosis of isolated clubfeet generally have a good prognosis. (25) Thorough phenotypic assessment at birth is warranted in order to detect signs of genetic syndromes not identified prenatally.

Postnatal management of clubfoot has changed in the past 10 years. Evidence from long term follow-up studies on children treated with minimally invasive procedures, such as Ponseti’s or Kite’s methods (25-27), significantly decreased the rate of a more extensive surgical treatment. Ponseti’s technique consists of sequential, manipulative castings and prolonged bracing, followed by eventual minor surgery, and is currently considered the best approach for children with isolated clubfoot (25,28).

Previous studies have suggested a higher risk of abnormal neurodevelopmental outcome in fetuses with clubfeet. However, the small number of cases included, the lack of standardized tools for assessment and heterogeneity in times at follow-up among the studies represent a significant bias in these studies. Longitudinal assessment by a pediatric neurologist is advisable in order to confirm a normal neurological development.

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