The pathogenesis of club foot. A histomorphometric and immunohistochemical study of fetuses

Abstract

We studied 16 club feet and 27 normal feet from spontaneously aborted human fetuses in the second trimester of gestation and measured the length of the spring ligament, and the declination angle and size of the talus. We also studied the cellular characteristics of the spring ligament and the immunohistochemical features of the medial ankle ligaments using monoclonal antibodies against type-Ill collagen, desmin, vimentin, and smooth muscle actin. Histomorphometric results indicated that the talar deformity was not the primarylesion. Histological and immunohistochemical findings showed that the cells and collagen fibres of the medial ankle ligaments of club feet appeared to be the site of the earliest changes, in that they had lost their spatial orientation and had contracted. In severe club feet before the third trimester of gestation, myofibroblast-like cells seemed to create a disorder ofthe ligaments resembling fibromatosis. This led to contraction and resulted in typical club-foot deformity.

Functional Assessment of Clubfoot Associated HOXA9, TPM1, and TPM2 Variants Suggests a Potential Gene Regulation Mechanism

“…The observed decrease in promoter activity with the alternate allele of rs3801776/ HOXA9 (Fig. 3C) could lead to alterations in muscle structure, calf muscle size, and slow and fast-twitch muscle composition, all of which have been reported in clubfoot [17,24,25]. The maturing of myoblasts (differentiated muscle cells) into long, multinucleated muscle fibers facilitates the functional properties of muscle such as contraction, which is a highly regulated process involving many proteins including TPM1 in the quick, easily fatigued fast-twitch muscle fibers and TPM2 in the slow, long contracting, slow-twitch fibers [18].…”

Tibialis Anterior Tendon Transfer after Clubfoot Surgery

“…The normal ratio of type I to type II fibers is 1:2 but in clubfeet the relationship is approximately 7:1. There are also collagen [12,18], myoblast [18], and occasionally arterial abnormalities [51] in children with clubfeet. These findings are in contrast to previous etiological theories suggesting malformation of the talus was the primary abnormality [32,48,49].…”

Pé torto congênito

“…The deltoid ligament and the plantar calcaneonavicular ligament ("spring ligament") are shortened and thickened. 42,55,58,59 Moreover, in CC, the calf muscles are smaller 1,12,28,50,56,57,60,61 , the foot size, as a whole, and that of the bones, individually, is also smaller 50 . Thus, the triceps surae muscle is invariably contractured and shortened [16][17][18], 50, 55-58 , although it is not clear whether the shortening is primary or secondary.…”

“…16,18,21,22,24,26,40 The cytocontractile proteins and myofibroblasts identified in the posteromedial contractured tissues of the hindfoot 30,34 are structurally similar to those present in palmar fibromatosis and express high levels of type III collagen and certain growth fac-tors, when compared to the non-contractured tissues. 41,42 Shortening, fibrosis and retraction of the muscles and ligaments in CC are said to be genetically induced, resulting in abnormal retraction capacity that could possibly be related to primary congenital deformities and also to relapses that occur, even after adequate treatment. Genetic factors may be involved in the origin of CC as suggested by studies that evidenced an increase in family incidence and in identical twins.…”