Review Question - QID 4442

Figure C shows the classic radiograph found in a child with achondroplasia, which is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3). Characteristic features include the "champagne glass" pelvis, squared iliac wings, and a flat acetabular roof.

Achondroplasia is an autosominal dominant condition caused by a mutation in fibroblast growth factor 3. The mutation causes a change in the genetic make-up of a single protein, changing glycine to arginine at position 380. Characteristic clinical features include rhizomelic dwarfism, frontal bossing, trident hands, and excessive lordosis secondary to congenitally short pedicles.

He et al. discuss the role of the G380R mutation in the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3), which is associated with achondroplasia. They demonstrated that FGFR3 WT/G380R heterodimers form with lower probability than wild-type FGFR3 homodimers at low ligand concentration.

Van Dijk et al. performed multiplex ligation-dependent probe amplification analysis of the COL1A1 gene in a group of 106 patients with a clinical suspicion of osteogenesis imperfecta (OI). They found a deletion of the complete COL1A1 gene on one allele in four families with mild OI.

Incorrect Answers:
Answer 1: Figure A represents rickets with metaphyseal cupping and fraying in the distal radius and ulna.
Answer 2: Figure B shows a radiographic representation of osteopetrosis caused by a genetic defects in osteoclast formation and function.
Answer 4: Figure D represents osteogenesis imperfecta, with marked osteopenia, anterior and medial bowing, and focal sclerosis in the midshaft of the tibia due to prior fracture. Osteogenesis imperfecta is associated with a gene mutation in collagen type I (COL1A2).
Answer 5: Figure E repesents cleidocranial dysplasia, with hypoplasia of the clavicles, an autosomal dominant defect in RUNX2 gene