Journal of Down Syndrome & Chromosome Abnormalities
Open Access

Pathophysiology of McCune-Albright Syndrome

Leonard Shepherd^{* *}Correspondence: Dr. Leonard Shepherd, Department of Genetics, University of Washington School of Medicine, Seattle, USA, Email:

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Description

The hallmark symptoms of McCune-Albright syndrome (MAS) are precocious puberty, skin patches, and Fibrous Dysplasia of the bone (FD). With an estimated prevalence of between 1/100,000 and 1/1,000,000, it is a rare disease. FD can show as a limp, discomfort, and possibly a pathologic fracture and can affect one or more skeletal locations. Scoliosis is a common condition that can progress. Other hyper functioning endocrinopathies, such as hyperthyroidism, excess growth hormone, Cushing syndrome, and renal phosphate wasting, may also be present in addition to PP, which is characterized by vaginal bleeding or spotting, the development of breast tissue. Although spot typically emerge during the new-born period, PP or FD is typically the ones that cause them, to consult doctor for treatment. Approximately 50% of MAS patients have renal problems. Somatic GNAS gene mutations, more especially mutations in the Gs alpha protein that controls cAMP, are the cause of the disease. The proliferation, migration, and survival of the cell in which the mutation occurs spontaneously during embryonic development define the severity of the disease. The diagnosis of MAS is typically made based on clinical evidence. Simple radiographs are frequently enough to diagnose FD, and FD lesions can be biopsied to confirm the diagnosis. The range of tissues that may be involved in MAS patients' evaluations should serve as a guide and each should undergo specific testing. Genetic testing is not always accessible but is still a possibility. However, genetic counseling ought to be made available. Neurofibromatosis, osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty, and ovarian neoplasm are examples of an alternative diagnoses. The tissues damaged and how severely they are impacted determine the course of treatment. Typically, some kind of surgical procedure is advised. The treatment of FD typically involves the use of bisphosphonates. To assist preserve the muscle around the FD bone and reduce the chance of fracture, strengthening activities are advised. All endocrinopathies must be treated. Malignancies connected to MAS are extremely uncommon. Less than 1% of instances with MAS result in the malignant transformation of FD lesions.

GTPase activity

Activating mutations in GNAS, which encodes the -subunit of the G-coupled protein receptor, are the cause of MAS due to the intrinsic GTPase activity of the -subunit being lost as a result of these mutations, constitutive receptor activation, and incorrect cAMP generation result. A crucial part of the GTPase, Arg201, is also where pathogenic mutations most frequently occur. More than 95% of missense mutations that cause disease are found at the R201H and R201C locations; sporadic mutations may also be found at the Q227 and other regions early on in the process of embryogenesis, somatic mutations in MAS take place. The amount and location of tissue harbouring mutations strongly influence the final phenotype. MAS are not inherited, and there are no known instances of vertical transmission, which is consistent with mosaic illness. The disease appears to affect all ethnic groups, and neither genetic nor environmental risk factors are currently identified The hyper functioning endocrinopathies that characterize MAS are caused by constitutive, ligand-independent signaling through the LH, FSH, TSH, GHRH, and ACTH receptors. Constitutive Gs activation in bone hampers skeletal stem cell differentiation, which results in the replacement of healthy bone and marrow with immature woven bone and fibrotic stroma.

Conclusion

Girls are more likely to experience McCune-Albright syndrome, which includes excess growth hormone and early puberty. Patients have advanced age and increased linear growth and early and effective management of both disorders results in decreased growth rate and stabilized bone age. When pediatric patients are identified with growth hormone excess, the anticipated adult and final heights are not adversely impacted.