Pseudoachondroplasia

Pseudoachondroplasia is caused by autosomal dominant mutations in the gene for cartilage oligomeric matrix protein (COMP), a large pentameric extracellular-matrix glycoprotein of cartilage (and tendon). The mutations - mostly in the calcium-binding domains - compromise protein folding, so the abnormal COMP is retained within the chondrocyte endoplasmic reticulum rather than secreted. This makes pseudoachondroplasia (with some forms of multiple epiphyseal dysplasia, its allelic "COMPopathy" partner) an ER storage disorder: the retained protein triggers ER stress, oxidative and inflammatory processes, chondrocyte death, and consequent loss of long-bone growth.

Unlike achondroplasia (which is evident at birth with characteristic facies), pseudoachondroplasia has no specific clinical or radiological findings at birth; the features develop slowly through childhood. A careful history and serial examination/radiographs make the diagnosis as the characteristic short stature, gait and skeletal changes appear.

The radiographic signature combines:

• Epiphyseal dysplasia - small, irregular, fragmented epiphyses (especially at the hips and knees).
• Metaphyseal dysplasia - irregular, flared/widened metaphyses.
• Spine involvement - platyspondyly (flattened vertebrae), often with anterior vertebral beaking/tonguing.
• Short tubular bones with brachydactyly (short metacarpals/phalanges). This combined epiphyseal-and-metaphyseal-and-spinal picture, in a child who was normal at birth, characterises pseudoachondroplasia.

Management is multidisciplinary and largely orthopaedic and supportive: monitor growth and deformity, correct lower-limb malalignment (guided growth in the growing child, osteotomy later), manage early osteoarthritis (and ultimately arthroplasty), address spinal deformity and cervical instability, and provide genetic counselling. There is no disease-modifying drug; care focuses on preserving function and preventing complications.