McCune-Albright syndrome with kyphosis challenges in diagnosis and treatment: a rare male case report

McCune-Albright syndrome (MAS) is a rare multisystem disorder defined by fibrous dysplasia (FD), café-au-lait pigmentation, and hyperfunctioning endocrinopathies, resulting from post-zygotic somatic activating pathogenic variants in GNAS. This report describes a 14-year-old boy with severe polyostotic FD and spinal involvement, emphasizing diagnostic delay and the complexities of individualized management. Although referred for progressive thoracic kyphosis and back pain, skeletal manifestations began at age 8 with a distal radius fracture, followed by impaired fracture healing and severe femoral pain. Imaging revealed extensive polyostotic FD with significant spinal involvement and thoracic kyphosis (T2-T11, 39°). MRI demonstrated a taut appearance of the thoracic spinal cord, suggesting increased cord tension associated with the kyphotic deformity, without definite evidence of spinal cord compression or neurological deficits. Endocrine assessment identified biochemical hyperthyroidism with suppressed thyroid-stimulating hormone, hyperprolactinemia, and elevated bone turnover markers. Whole-exome sequencing of lesional bone detected a somatic GNAS c.602G>A (p.Arg201His; R201H) pathogenic variant, absent in peripheral blood. In the absence of neurological impairment or progressive severe spinal deformity necessitating surgery, management included methimazole, a thoracolumbar brace, and individualized off-label denosumab. Over 24 months of follow-up, skeletal pain improved markedly, with no progression of kyphosis or new pathological fractures. After extending the denosumab dosing interval, bone turnover markers partially rebounded, while serum calcium remained within normal limits. This case underscores the importance of early recognition of FD/MAS skeletal manifestations to minimize diagnostic delay. Denosumab may offer symptomatic and biochemical benefits in selected severe cases; however, its use in pediatric patients remains non-standard, with unresolved questions regarding optimal dosing and the risks of rebound bone turnover and hypercalcemia, necessitating careful long-term monitoring.