Makindo Medical Notes

Related Subjects: |Adrenal Physiology |Addison's Disease |Phaeochromocytoma |Adrenal Adenomas |Adrenal Cancer |Cushing Syndrome |Cushing Disease |Congenital Adrenal hyperplasia |Primary hyperaldosteronism (Conn's syndrome) |ACTH |McCune Albright syndrome

There is very strong evidence that McCune-Albright Syndrome (MAS) is caused by somatic mutations in the GNAS gene. It is a sporadic disorder, meaning it is not inherited but results from a random, somatic mutation.

About

• McCune-Albright Syndrome is a disorder that affects the skin, skeleton, and certain endocrine organs.
• Red cell failure usually presents in a child younger than 1 year.
• Presence of congenital anomalies. Cancer predisposition.

Genetics

• Caused by somatic mutations in the GNAS gene.
• It is caused by a random, somatic mutation not inherited.

Aetiology

• Precocious puberty due to oestrogen from ovarian cysts.
• Cushing's syndrome due to excess cortisol release.

Clinical Features

• Precocious puberty, e.g., menstruation at age 2.
• Precocious puberty seen rarely in boys with development of genitalia.
• Bony fibromas and dysplasias, leading to pathological fractures.
• Thyrotoxicosis, osteomalacia - tender bones, etc.
• Cafe-au-lait spots (also seen in Neurofibromatosis).
• Acromegaly, hypothyroidism, hypoparathyroidism.
• Cushing's syndrome.

Differential Diagnoses

• Neurofibromatosis Type 1 (NF1)
• Other endocrine disorders causing precocious puberty
• Other causes of cafe-au-lait spots
• Skeletal dysplasias and fibrous dysplasia

Investigations

• Blood Tests: Low Calcium, Raised Alkaline Phosphatase (ALP). Low Phosphate levels.
• Endocrine Evaluation: Assess hormone levels (e.g., cortisol, thyroid hormones).
• Skeletal Survey: Identify fibrous dysplasia and skeletal abnormalities.
• Imaging Studies: X-rays, MRI, or CT scans to assess bone lesions and endocrine organs.
• Genetic Testing: Identification of GNAS mutations.

Management

• Endocrinology review for hormonal imbalances.
• Orthopaedic review for skeletal abnormalities and fractures.
• Regular monitoring and management of endocrine dysfunctions.
• Bisphosphonates may be used to strengthen bones in cases of fibrous dysplasia.
• Surgical intervention for severe skeletal deformities or fractures as needed.
• Psychosocial support and counseling for affected individuals and families.
• Typically, individuals with MAS have a normal life span with appropriate management.

Prognosis

• Generally, individuals with McCune-Albright Syndrome have a normal life span with proper management of symptoms and complications.
• Early diagnosis and treatment of endocrine and skeletal abnormalities are crucial for optimal outcomes.
• Regular follow-up is necessary to monitor and manage potential complications such as fractures, endocrine dysfunctions, and cancer predisposition.

Conclusion

McCune-Albright Syndrome is a complex, multisystem disorder characterized by fibrous dysplasia of the bones, endocrine abnormalities, and distinctive skin pigmentation. Caused by somatic mutations in the GNAS gene, it presents in early childhood with varying manifestations depending on the affected systems. Comprehensive management involving endocrinologists, orthopaedic surgeons, and other specialists is essential to address the diverse clinical features and improve patient outcomes. Early intervention and regular monitoring play pivotal roles in minimizing complications and enhancing the quality of life for individuals with MAS.

References

• National Institutes of Health (NIH) - McCune-Albright Syndrome
• Mayo Clinic - McCune-Albright Syndrome
• Medscape - McCune-Albright Syndrome Overview
• NCBI - McCune-Albright Syndrome: Pathophysiology and Clinical Features
• eMedicineHealth - McCune-Albright Syndrome
• Rowe, S. M., et al. (2001). McCune-Albright Syndrome. In *GeneReviews*. University of Washington, Seattle.