Synpolydactyly of the foot in homozygotes

In 2002, we reinvestigated a large synpolydactyly kindred first described in 1995. It was found to have expanded with an increase in number of homozygous offspring. These homozygotes had severe hypoplasia, with synpolydactyly of their hands and feet. We present the clinical, genetic, and surgical findings of this deformity and the histologic findings of the removed bones of the heterozygous and homozygous members. There were 125 affected individuals (113 heterozygotes and 12 homozygotes) of 245 members of the past five generations. We identified seven marriages in which both spouses were affected. Twelve offspring from these marriages had homozygote genetic patterns, hypoplastic synpolydactyly of the hands, and a distinctive foot deformity, with a prominent great toe and syndactylized hypoplastic minor toes. From clinical and surgical perspectives, their hand and foot deformities were different from those of their parents. We surgically treated both feet of four individuals with this deformity, which we called "homozygote foot synpolydactyly." Clinically, the deformity consisted of a supinated prominent great toe, hypoplastic and severely synpolydactylized minor toes, and secondary problems. Radiographically, the bones were underdeveloped, unshaped, and largely fused. Abundant cartilage covering the bones was observed surgically and histologically. Genetically, analysis of HOXD13 identified a 27-base pair duplication with a homozygote pattern. The foot deformity of the homozygotes was so distinctive and complicated that it should be considered a separate foot synpolydactyly type--homozygote foot synpolydactyly.