McCune Albright Syndrome (MAS, OMIM # 174800) is a rare congenital sporadic disorder with an estimated prevalence ranging from 1 in 1,00,000 to 1 in 100,000. MAS is caused by a post-zygotic somatic activating mutation of the GNAS1 gene resulting in an increased GSα protein signaling leading to hyperfunction of glycoprotein hormone receptors, autonomous cell proliferation, and hormonal hypersecretion. The mosaic constitutive activation of this signal transducer is clinically evident with a scattered hyperfunction of endocrine tissues with a wide phenotypic spectrum. MAS classical phenotype includes the clinical triad of bone fibrous dysplasia (BFD), café-au-lait skin spots due to skin dysplasia, and peripheral precocious puberty (PPP). However other endocrinopathies as hyperthyroidism, hypercortisolism, hyperpituitarism, kidney phosphate wasting, can be present.
Precocious puberty (PPP): treatment prevents bone age advancement and compromise of adult height. For girls, the aromatase inhibitor letrozole is used; for boys, treatment options include aromatase inhibitor and androgens receptors blockers Thyroid disease:methimazole effectively manages hyperthyroidism; however, because hyperthyroidism is persistent, thyroidectomy is possible. Growth hormone excess: medical therapy is the preferred first-line treatment; options include (alone or in combination) octreotide and the growth hormone receptor antagonist pegvisomant. Hypercortisolism: treatment varies by the presentation of neonatal Cushing syndrome.
Surveillance of endocrinophaties is mandatory. Infants: clinical signs of hypercortisolism. All children: growth acceleration and other clinical signs of precocious puberty and/or growth hormone excess. Children: Age <5 years: thyroid function abnormalities. With thyroid abnormalities on ultrasound examination but normal thyroid function: periodic monitoring of thyroid function. Males: testicular lesions (physical examination and testicular ultrasound). Females: breast cancer (earlier than is recommended for the general population). Check routinely phosphorus levels related to age to correct phosphate wasting that can worse bone quality and pain.