Primary bone dysplasia with disorganized development of skeletal components
-Rare bone disease
-Rare developmental defect during embryogenesis
-Rare genetic disease
Beighton et al. (1980) described a seemingly 'new' form of dwarfism in a 10-year-old South African girl of mixed ancestry. The designation 'osteoglophonic,' which connotes 'hollowed out,' was based on the radiographic appearance of the metaphyses. The dwarfism ... Beighton et al. (1980) described a seemingly 'new' form of dwarfism in a 10-year-old South African girl of mixed ancestry. The designation 'osteoglophonic,' which connotes 'hollowed out,' was based on the radiographic appearance of the metaphyses. The dwarfism was rhizomelic and the facies was grossly distorted with very marked depression of the nasal bridge, frontal bossing, and prognathism--a caricature of achondroplasia. Cystic changes like those of fibrous dysplasia were combined with the radiographic appearance of an unusual spondyloepimetaphyseal dysplasia. Reports of 2 previous cases were found. Fairbank (1951) described a severely dwarfed male at ages 10 and 24 years. Biopsy of a 'lytic' lesion in the patient of Keats et al. (1975) showed benign, whorled, fibrous tissue. In the patient of Beighton et al. (1980), the parents were nonconsanguineous and the father was 39 years old at her birth, supporting dominant inheritance. Dominant inheritance seems established by the report of affected father and son by Kelley et al. (1983). Craniosynostosis took the form of 'Kleeblattschaedel.' Symmetrical lucent metaphyseal defects were present in most long bones. McKusick (1980) stated that he and his colleagues had entertained the diagnosis of osteoglophonic dwarfism in a 2-month-old child who had bowing of the long bones with overlying dimples, and craniosynostosis of a single suture leading to plagiocephaly. The metaphyses showed striking cystic changes. The ribs were involved. The radiologic features superficially resembled those of Ollier disease (166000). The infant, however, was found to have hypophosphatasia (241500). This deficiency, including the biochemically variant form described by Scriver and Cameron (1969), should be sought in other cases of 'osteoglophonic dwarfism' (Reid, 1984). It is noteworthy that White et al. (2005) demonstrated hypophosphatemia secondary to renal phosphate wasting in patients with this disorder, and demonstrated a correlation with circulating levels of fibroblast growth factor-23 (FGF23; 605380). FGF23 had been shown to be produced by the nonossifying lesions in some patients with fibrous dysplasia of bone (Riminucci et al., 2003). The nonossifying lesions of dysplasia presumably produce FGF23 to account for the hypophosphatemia. Santos et al. (1988) described a boy with features typical of osteoglophonic dwarfism who died suddenly at the age of 10 months. See review by Beighton (1989).
White et al. (2005) demonstrated that osteoglophonic dysplasia is caused by missense mutations in highly conserved residues comprising the ligand-binding and transmembrane domains of FGFR1 (see, e.g., 136350.0008-136350.0010), thus defining novel roles for this receptor as a negative ... White et al. (2005) demonstrated that osteoglophonic dysplasia is caused by missense mutations in highly conserved residues comprising the ligand-binding and transmembrane domains of FGFR1 (see, e.g., 136350.0008-136350.0010), thus defining novel roles for this receptor as a negative regulator of long-bone growth. A diverse group of skeletal disorders is caused by activating mutations in the genes encoding fibroblast growth factor receptors 1-3: FGFR1, FGFR2 (176943), and FGFR3 (134934). In general, mutations in FGFR1 and FGFR2 cause most of the syndromes involving craniosynostosis, whereas the dwarfing syndromes are largely associated with FGFR3 mutations. Osteoglophonic dysplasia is a 'crossover' disorder that has skeletal phenotypes associated with mutations in all 3 fibroblast growth factor receptors. Farrow et al. (2006) identified a mutation in the FGFR1 gene (136350.0012) in the patient with OGD originally reported by Beighton et al. (1980).