What is McCune-Albright Syndrome (MAS)?

From the Guidelines

McCune-Albright syndrome is a rare genetic disorder characterized by the triad of café-au-lait skin spots, polyostotic fibrous dysplasia, and endocrine abnormalities, and its management should prioritize minimizing morbidity, mortality, and improving quality of life. When considering the treatment of GH excess in the context of McCune-Albright syndrome, it is crucial to weigh the risks and benefits of different approaches, given the potential for sarcomatous transformation with radiotherapy 1. The condition results from a mutation in the GNAS gene, leading to overactive cellular signaling, and its manifestations include:

• Café-au-lait skin spots with irregular borders
• Polyostotic fibrous dysplasia, which can cause pain, deformity, and fractures
• Endocrine abnormalities, such as precocious puberty, hyperthyroidism, growth hormone excess, and Cushing syndrome Given the complexities of McCune-Albright syndrome, treatment should be individualized and may include medical therapies to manage hormonal issues, bisphosphonates for bone pain, and surgery for severe bone deformities, while avoiding radiotherapy due to the risk of sarcomatous transformation, as suggested by the uncertain transforming effect of GH-IGF1 on dysplastic bone 1. Regular monitoring by a multidisciplinary team of specialists, including endocrinologists and orthopedists, is essential for managing this lifelong condition and preventing complications. Key aspects of management include:
• Monitoring for endocrine abnormalities and adjusting treatment as needed
• Managing bone lesions to prevent pain, deformity, and fractures
• Addressing skin manifestations and other symptoms
• Preventing long-term complications, such as pathologic fractures, vision or hearing loss, and hormonal imbalances, which is in line with the recommendation to offer intermittent dose reduction or withdrawal of medical therapy to assess radiation efficacy on GH hypersecretion, although this should be done with caution in the context of McCune-Albright syndrome 1.

From the Research

Definition and Characteristics of McCune Albright Syndrome

• McCune Albright syndrome (MAS) is a rare disease characterized by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP) 2.
• The disease results from somatic mutations of the GNAS gene, specifically mutations in the cAMP regulating protein, Gs alpha 2, 3.
• The extent of the disease is determined by the proliferation, migration, and survival of the cell in which the mutation spontaneously occurs during embryonic development 2.

Clinical Features and Diagnosis

• Patients with MAS present clinically with a variable combination of FD, café-au-lait skin macules, and hyperfunctioning endocrinopathies 3.
• Café-au-lait spots usually appear in the neonatal period, but it is most often PP or FD that brings the child to medical attention 2.
• Diagnosis of MAS is usually established on clinical grounds, with plain radiographs often sufficient to make the diagnosis of FD, and biopsy of FD lesions can confirm the diagnosis 2.
• Genetic testing is possible, but is not routinely available, and genetic counseling should be offered 2.

Treatment and Management

• Treatment is dictated by the tissues affected, and the extent to which they are affected, with some form of surgical intervention often recommended 2.
• Bisphosphonates are frequently used in the treatment of FD, and strengthening exercises are recommended to help maintain the musculature around the FD bone and minimize the risk for fracture 2.
• Treatment of all endocrinopathies is required, and a systematic approach to diagnosis and management is critically important to optimize outcomes for patients with FD/MAS 3.

Complications and Prognosis

• Malignancies associated with MAS are distinctly rare occurrences, with malignant transformation of FD lesions occurring in probably less than 1% of the cases of MAS 2.
• Non-endocrine manifestations, such as fibrous dysplasia of bone, renal phosphate wasting, and skin hyperpigmentation, can also occur, and the prognosis depends on the severity of each individual endocrine manifestation 4.
• Recent data have drawn attention to non-endocrine affections, including hepatobiliary dysfunction and cardiac disease, which are probably an important risk factor for early death 4.