Review Question - QID 220892

Achondroplasia is characterized by a gain-of-function mutation in the FGFR3 gene, which leads to skeletal dysplasia secondary to inhibited chondrocyte proliferation in the proliferative zone (Answer 2).

Achondroplasia is an autosomal dominant form of skeletal dysplasia caused by a gain-of-function mutation in the FGFR3 gene. This subsequently leads to upregulation of pathways involved in the inhibition of bony growth. STAT1, one of these unregulated pathways, inhibits chondrocyte proliferation in the zone of proliferation within the physis. Patients with this condition typically present with short stature, delayed motor development, frontal bossing, normal intelligence, and hearing impairment.

Ballock and O’Keefe published a review covering physis biology. They cover the biological makeup of each physis layer, the biochemical pathways that regulate the cells of each layer, and their contributions to overall long bone growth. They concluded that understanding the biology of the physics that contribute to bony growth is crucial in the development of treatments that address injuries or abnormalities of the growth plate.

Hosseinzadeh and Milbrandt reviewed the normal function and anatomy of the physis and discuss the potential insults that may occur to this structure, leading to abnormal growth phenotypes. They cover Salter-Harris injuries and their potential for physeal bar formation. They describe that bar resection should be performed in patients with more than two years of growth left who have bars < 50% of the physis cross-sectional area. These procedures are additionally accompanied by interposition of material such as fat, polymethylmethacrylate, silastic, fibrin, or dura substitute. They concluded that understanding of the molecular processes at the level of each physis layer is paramount for developing modalities to address physeal injuries.

Figure A is an unlabeled depiction of the layers of the epiphysis, physis, and metaphysis.
Illustration A is a labeled depiction of the layers of the epiphysis, physis, and metaphysis.

Incorrect Answers:
Answer 1: The layer labeled A represents the resting zone. This is where vital components required for growth are stored. Abnormalities in this anatomic area lead to Gaucher’s Diatrophic dysplasia and pseudoachondroplasia.
Answer 3: The layer labeled C represents the zone of hypertrophy, where chondrocytes mature, hypertrophy, and calcify. Abnormalities in this anatomical area can lead to enchondromas, slipped capital femoral epiphysis, and Rickets.
Answer 4: The layer labeled D represents the zone of provisional calcification, which is where chondrocyte death occurs, leading to calcium release and resultant calcification.
Answer 5: The layer labeled E represents the metaphysis, where mineralization of primary spongiosa occurs.