Clubfoot is a birth defect where a newborn’s foot is twisted inward and downward. The condition results from tendons in the leg and foot being shorter than usual, which pulls the foot into an abnormal position. While it can range from mild to severe, it is a treatable condition, especially when addressed shortly after birth. Clubfoot does not have a single, definitive cause; its development is considered multifactorial, stemming from a complex interplay between genetic and environmental influences.
The Genetic Link to Clubfoot
There is strong evidence for a genetic basis for isolated clubfoot, with about 25% of cases reporting a family history of the condition. Rather than being caused by a single gene, clubfoot is understood as a polygenic trait, meaning variations in multiple genes combine to increase an individual’s susceptibility. No single gene guarantees the condition will manifest, but inheriting a specific combination of these genetic variants creates a predisposition.
Among the genes studied, those within the PITX1-TBX4 pathway are of significant interest. These genes are involved in the normal development of the hindlimb, and variations in this pathway have been directly linked to clubfoot. For example, specific mutations in the PITX1 gene and duplications of the TBX4 gene have been identified in individuals with the condition.
Other gene groups, such as homeobox (HOX) genes and those responsible for muscle contraction, have also been associated with clubfoot. HOX genes play a part in the organizational patterning of the developing fetus, and certain variants are linked to clubfoot phenotypes. Similarly, mutations in genes that code for muscle proteins can lead to the types of joint and muscle issues seen in some forms of the condition. The combined effect of these genes establishes a genetic risk.
Associated Environmental Factors
While genetics can lay the groundwork for clubfoot, environmental factors during pregnancy can act as triggers. One of the most frequently cited factors is maternal smoking. The use of tobacco during pregnancy has been associated with a higher risk of the baby developing clubfoot, particularly in a fetus that may already have a genetic predisposition.
The physical environment within the womb is another contributor. A condition known as oligohydramnios, where there is an insufficient amount of amniotic fluid, can increase the risk. This reduced fluid can restrict fetal movement, preventing the feet from developing in a normal position. The baby’s positioning in the uterus can similarly limit space and contribute to the foot being held in an abnormal orientation.
Other maternal health factors and exposures are also under investigation. For instance, studies have noted associations between clubfoot and maternal obesity or gestational diabetes. The use of certain medications, such as selective serotonin reuptake inhibitors (SSRIs), during pregnancy has also been identified as a potential risk factor.
Family Recurrence and Syndromic Conditions
The likelihood of clubfoot is higher in families with a history of the condition. While the incidence in the general population is about 1 in 1,000 births, the risk increases if a close relative is affected. If a parent has clubfoot, their child has a greater chance of being born with it, and the risk is even more pronounced for siblings.
There are two main types of clubfoot. The most common form is isolated (or idiopathic) clubfoot, which occurs in about 80% of cases. In these instances, clubfoot is not associated with any other medical problems and is the only health issue present.
In the remaining 20% of cases, clubfoot is considered syndromic, meaning it is one component of a broader genetic syndrome or chromosomal abnormality. Conditions such as spina bifida, a neural tube defect, or Edwards syndrome (Trisomy 18) can have clubfoot as one of their features. Identifying whether clubfoot is isolated or part of a syndrome is important for understanding the child’s overall health.