We recently found mutations of the transforming growth factor beta 1 (TGF-beta1) gene (TGFB1) in 9 families, in which progressive diaphyseal dysplasia (Camurati-Engelmann disease) is segregating [Kinoshita et al., 2000: Nat Genetics 26:19-20]. During the study, we encountered two unrelated girls, aged 17 and 11 years, who had clinical manifestations of the disorder, such as marfanoid habitus, waddling gait, muscular weakness, intense leg pain, flexion contracture of the hip and knee joints, delayed sexual development, increased serum alkaline phosphatase levels, and increased erythrocyte sedimentation rates. Radiographic studies in the two girls demonstrated not only diaphyseal dysplasia (cortical thickening of the diaphyses) resembling that of progressive diaphyseal dysplasia but also metaphyseal expansion of the long bones, coarse and thick trabeculae of the long and short tubular bones, striations in the spinal, pelvic, and long bones, and cranial sclerosis restricted to the petromastoid regions. These radiographic changes were overall identical with those seen in hyperostosis generalisata with striations of the bones rather than those in progressive diaphyseal dysplasia. Polymerase chain reaction-direct sequencing of all exons and their flanking regions of TGFB1 did not detect any mutations. PCR-single strand conformational polymorphism analysis of the TGF-beta type 1 receptor gene (TGFBR1) did not demonstrate any aberrant DNA fragments. We concluded from these findings that the two girls we described belong to a unique entity distinct from either of the two disorders.
Copyright 2001 Wiley-Liss, Inc.