Genotype-Phenotype Correlation in Fibrous Dysplasia/McCune-Albright Syndrome Patients With Craniofacial Lesions.

Objectives: We aimed to investigate genotype-phenotype correlations, variant prevalence, and prognostic factors in a Chinese cohort with craniofacial FD/MAS.

Methods: A retrospective study of 93 histologically confirmed FD/MAS cases (2003-2024) analyzed GNAS mutations via direct sequencing. Clinical data, including disease onset, lesion activity (active vs. stable), and extraskeletal manifestations, were correlated with genotypic findings.

Results: R201H was the predominant variant (58.1% vs. 41.9% R201C), with no significant differences in demographics, symptoms, or prognosis between genotypes. Active lesions (34.6%) exhibited earlier disease onset (8.0 vs. 12.0 years, p = 0.026), higher rates of bilateral involvement (51.9% vs. 27.5%, p = 0.033), pain (37.0% vs. 9.8%, p = 0.004), and nasal obstruction (25.9% vs. 2.0%, p = 0.003). MAS was strongly associated with active lesions (25.9% vs. 3.9%, p = 0.026), while monostotic FD predominated in stable lesions. All three cases of osteosarcoma harbored R201C; though statistical significance was not reached.

Conclusions: This study showed no genotype-phenotype correlations in FD/MAS but highlights R201H as the major variant in this population. Active lesions correlate with early onset, bilateral craniofacial involvement, and MAS, warranting close monitoring. R201C's link to malignancy, though inconclusive, suggests possible variant-specific differences in malignant transformation.