Byrnes et al. (2010) studied a consanguineous French Canadian family in which 3 sibs had type A1 brachydactyly. Radiographs and metacarpophalangeal profiles of the proband showed significantly shortened middle phalanges of digits 2 to 5 as well as ... Byrnes et al. (2010) studied a consanguineous French Canadian family in which 3 sibs had type A1 brachydactyly. Radiographs and metacarpophalangeal profiles of the proband showed significantly shortened middle phalanges of digits 2 to 5 as well as the first distal phalanx. A very short first metacarpal was observed, giving the appearance of a proximally placed thumb. The third to fifth metacarpals showed less marked shortening, and the ulnar styloid process was truncated. The feet were similarly affected. The proband and an affected sister were both 5 feet tall (5th centile) and both were treated for clubfeet as children; neither had fibular hypoplasia. Their affected brother was 5 feet 6 inches tall (10th centile), and all 3 affected sibs were shorter than their 2 unaffected sisters. The proband had a son who was of average height and appeared to be unaffected; however, radiography revealed subtle but significant changes, and his metacarpophalangeal profile showed that the middle phalanges of the second to fifth digits were short and below -2 SD when controlled for age and sex, and his first metacarpal was also short.
In 3 affected sibs from a consanguineous French Canadian family with type A1 brachydactyly mapping to chromosome 20q11, Byrnes et al. (2010) identified homozygosity for a missense mutation in the candidate gene GDF5 (R399C; 601146.0020). The proband's son, ... In 3 affected sibs from a consanguineous French Canadian family with type A1 brachydactyly mapping to chromosome 20q11, Byrnes et al. (2010) identified homozygosity for a missense mutation in the candidate gene GDF5 (R399C; 601146.0020). The proband's son, who had a milder phenotype, was heterozygous for the R399C mutation, consistent with a semidominant pattern of inheritance.