FRCS EMQs: Paediatric orthopaedics

Clinical Rationale: PEX.

Clinical Rationale: Core binding factor alpha-1 (CBFA1).

Clinical Rationale: X-linked recessive. Hypophosphataemic rickets is an example of an X-linked dominant condition where the defective PEX gene produces a non-functioning zinc-metalloproteinase. This enzyme usually breaks down FGF23 and its accumulation increases urinary excretion of phosphate and reduces alpha-1 hydroxylase activity. This accounts for the low serum phosphate and defective mineralization of bone. Males are often more affected than females due to the random inactivation of one of the X chromosomes in females. The condition characterized by absent clavicles is cleidocranial dysostosis. The CBFA1 gene encodes a transcription factor for osteocalcin that regulates intramembranous ossification. The mutant state produces a proportionate dwarfism where the defining feature is partial or complete unilateral or bilateral aplasia of the clavicles and problems with formation of the skull bones. Duchenne’s muscular dystrophy is an X-linked recessive condition that presents with muscle weakness, difficulty walking and a Gower’s sign on examination with pseudohypertrophy of some muscle groups. Gower’s sign involves using the arms to splint the legs when rising from the floor due to weakness in the gluteal and quadriceps muscles. The gene defect results in virtually no production of the dystrophin protein that is responsible for maintaining muscle cell structure; its absence leads to cell death. In Becker’s muscular dystrophy, a similar genetic defect exists that results in the production of defective dystrophin.