Abstract
McCune-Albright syndrome (MAS) is a rare mosaic disorder caused by somatic gain-of-function variants in GNAS and frequently associated with fibrous dysplasia (FD). FD-related complications impair physical function and quality of life (QOL), yet Japanese data are lacking. We conducted a nationwide survey to characterize functional impairment and physician-perceived QOL factors in patients with MAS in Japan. Data on 43 patients were collected using a web-based questionnaire sent to council members of the Japanese Society for Pediatric Endocrinology and the Japanese Society for Bone and Mineral Research. Motor disability was assessed using the Japanese version of the modified Rankin Scale (mRS); respiratory, visual, and hearing impairments were graded using the Japanese severity criteria for designated intractable diseases. Physicians identified the single factor perceived as most affecting each patient's QOL. Motor impairment was present in 72.1%, including moderate or severe impairment (mRS ≥3) in 30.2%; other impairments were each absent in more than 80%. The most frequent QOL-affecting factor was bone pain or fractures (37.2%), followed by facial deformity or appearance changes (18.6%) and mobility or physical activity limitation (16.3%). Physician-perceived QOL factors differed by mRS group (p < 0.001): bone pain and facial deformity predominated in patients with mRS <3, whereas mobility limitation predominated in those with mRS ≥3. These findings indicate that FD-related skeletal manifestations are a major source of disability and QOL burden in Japanese patients with MAS, supporting stratified management tailored to motor disability.