#119800
ICD+
| ||||||||||||||||||||||||||||||||||||||||||
| CLUBFOOT, CONGENITAL; CCF | ||||||||||||||||||||||||||||||||||||||||||
| Alternative titles; symbols | ||||||||||||||||||||||||||||||||||||||||||
| TALIPES EQUINOVARUS; TEV | ||||||||||||||||||||||||||||||||||||||||||
| Phenotype Gene Relationships | ||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||
| Clinical Synopsis | ||||||||||||||||||||||||||||||||||||||||||
| TEXT | ||||||||||||||||||||||||||||||||||||||||||
| A number sign (#) is used with this entry because of evidence that clubfoot can be caused by mutation in the PITX1 gene (602149) on chromosome 5q31. | ||||||||||||||||||||||||||||||||||||||||||
| Description | ||||||||||||||||||||||||||||||||||||||||||
| Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). For a review, see Dietz (2002). | ||||||||||||||||||||||||||||||||||||||||||
| Nomenclature | ||||||||||||||||||||||||||||||||||||||||||
| Barker et al. (2003) noted that the term 'clubfoot' has variably included both acquired and congenital talipes equinovarus, and historically has even included other conditions such as calcaneovalgus and metatarsus adductus. Moreover, within the congenital group, the distinction between syndromic and isolated subgroups has not been consistent. They concluded that it is sometimes difficult to ascertain the significance of differences between reported series. | ||||||||||||||||||||||||||||||||||||||||||
| Clinical Features | ||||||||||||||||||||||||||||||||||||||||||
| Gurnett et al. (2008) described a 5-generation North American family of European descent segregating clubfoot. The proband had bilateral clubfoot, bilateral foot preaxial polydactyly, and right-sided tibial hemimelia. Five additional family members had clubfoot, 3 of whom had increased severity on the right. Some family members had additional lower limb malformations including patellar hypoplasia, oblique talus manifesting as pes planus, and developmental hip dysplasia. No upper extremity abnormalities or dysmorphic craniofacial features were noted. | ||||||||||||||||||||||||||||||||||||||||||
| Inheritance | ||||||||||||||||||||||||||||||||||||||||||
| Clubfoot appears to be multifactorial trait. Gurnett et al. (2008) described a 5-generation family with asymmetric right-sided predominant clubfoot segregating as an autosomal dominant condition with incomplete penetrance. Palmer (1964) suggested that 2 groups may exist: (1) a group with normal sex ratio, normal maternal age curve, recurrence risk of about 10% and probable dominant inheritance with about 40% penetrance; and (2) a group born to younger mothers with preponderance of males and no clear pattern of inheritance. Book (1948) estimated that the risk of recurrence in subsequently born children in Caucasians is between 3 and 8% if 1 child is affected and about 10% if 1 child and 1 parent are affected. Chung et al. (1969) performed a large-scale study of talipes equinovarus in Hawaii. They found an overall male to female sex ratio of approximately 2 to 1, no significant differences between isolated and familial cases, and no evidence of a maternal age effect. The incidence of uncomplicated TEV by major racial groups adjusted for incomplete ascertainment was highest in Hawaiians (6.81/1000 births), followed by Caucasians (1.12/1000 births) and then East Asians (0.56/1000 births). Beals (1978) studied 50 consecutive Maori kindreds with a child with clubfoot who were treated at the same hospital in New Zealand during a 6-month period. The index patients were 31 males and 19 females. Empiric risk data indicated that if the index patient was female, the chance of subsequent children being affected was 4%, whereas if the index patient was male, the chance was 9%, and if parent and child were affected, the chance was 30%. These risks were much higher than those found in Caucasians by Book (1948) and Wynne-Davies (1964). As in Caucasians, inheritance appeared to be polygenic. The incidence of clubfoot in New Zealand Maori was estimated to be 6.5-7.0/1000 births. Wang et al. (1988) used updated data on families with clubfoot originally reported by Palmer (1964) and concluded that the segregation pattern in these families is best explained by assuming the action of a major gene with additional contribution of multifactorial inheritance. The mixed model suggested that the major gene behaves largely as a dominant. Chapman et al. (2000) analyzed the role of major gene and multifactorial inheritance in the etiology of clubfoot in the New Zealand Polynesian population by studying 287 clubfoot families. Using the computer program POINTER, they showed that the best genetic model for clubfoot in this population is a single dominant gene with a penetrance of 33% and a predicted gene frequency of 0.9%. | ||||||||||||||||||||||||||||||||||||||||||
| Molecular Genetics | ||||||||||||||||||||||||||||||||||||||||||
| In affected members of a 5-generation family segregating clubfoot, Gurnett et al. (2008) identified a missense mutation in the PITX1 gene (602149.0001). | ||||||||||||||||||||||||||||||||||||||||||
| Population Genetics | ||||||||||||||||||||||||||||||||||||||||||
| Kancherla et al. (2010) estimated the incidence of isolated club foot to be 11.4 per 10,000 livebirths in Iowa. Increased prevalence odds ratios (POR) were found for male sex (POR = 1.8) and maternal smoking during pregnancy (POR = 1.5). Low-birth weight showed an increased POR for females (POR = 3.2), but not males (POR = 0.9). | ||||||||||||||||||||||||||||||||||||||||||
| See Also: | ||||||||||||||||||||||||||||||||||||||||||
| Alberman (1965); Ching et al. (1969) | ||||||||||||||||||||||||||||||||||||||||||
| REFERENCES | ||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||