McCune-Albright syndrome in Child
MAS has an estimated prevalence of 1 in 100 000 worldwide and affects males and females with equal frequency. It is caused by sporadic mutations in Gs alpha subunit protein (GNAS) in the adenylyl cyclase-cyclic adenosine monophosphate (cAMP) pathway, which plays important roles in regulating the production and excretion of endocrine hormones, among many other biological processes. GNAS mutations in MAS result in a constitutively activated cAMP pathway and thereby the observed clinical phenotypes with an overproduction of several hormones. The mutations of MAS are sporadic and occur post-zygotically; as a result, the affected individuals are genetically mosaic and the clinical presentations of MAS are extremely variable depending on the degree to which each tissue is affected. Inherited cases of MAS do not occur as germline transmission of these mutations is not compatible with life.
The polyostotic fibrous dysplasia associated with MAS entails gradual replacement of bone by abnormal scar-like connective tissue that weakens the bones and makes them prone to fracture. This process can involve any bone but usually affects the long bones, pelvis, scapula, and skull base. In some patients, the clinical manifestations of polyostotic fibrous dysplasia are asymptomatic and detectable only by bone scan; in others, they are markedly disfiguring, with development of pathologic fractures and/or nerve impingements.
Patients usually have café au lait spots with irregular borders that have often been compared to the coastline of Maine, as seen on a map. These patches can be present at birth and become more numerous and darker with age. While the diagnosis of MAS could be considered if the characteristic café au lait macules are identified at birth, the diagnosis is often not made until later in childhood, when symptoms from bony fibrous dysplasia and endocrine dysfunction become more apparent.
Endocrine organ malfunctions can result in precocious puberty with premature development of secondary sexual characteristics. Female patients with MAS may reach early menarche due to the production of excess estrogens by benign ovarian cysts. Males may also experience early puberty with premature production of excess testosterone. Patients with MAS may also have other endocrine abnormalities, including the excess production of growth hormone (gigantism), thyroid hormone (hyperthyroidism), and adrenal hormones (Cushing syndrome).
Q78.1 – Polyostotic fibrous dysplasia
36517007 – Polyostotic fibrous dysplasia of bone
Differential Diagnosis & Pitfalls