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Double heterozygosity in bone growth disorders: Four new observations and review

Because matings between individuals of small stature is common, information regarding double heterozygosity for dominantly inherited bone growth disorders is of considerable importance. We summarize seven occurrences of four combinations of double heterozygosity (achondroplasia/spondyloepiphyseal dysplasia congenita, achondroplasia/pseudoachondroplasia, achondroplasia/osteogenesis imperfecta type I, achondroplasia/hypochondroplasia (non‐FGFR3)), and review additional reports from the literature. Each of the eight different examples of double heterozygosity for bone growth disorders now reported results in distinct phenotypic features, differing severity, and disparate expectations. We document the natural history of each. The genetic processes underlying these disorders also are examined to assess whether knowledge of molecular mechanisms can be used to predict clinical severity. © 2003 Wiley‐Liss, Inc.