Makindo Medical Notes

⚠️ Key Point: McCune-Albright Syndrome (MAS) is caused by somatic mutations in the GNAS gene. It is sporadic (not inherited) and results from a random, post-zygotic mutation.

ℹ️ About

• 🦴 A disorder affecting skin, skeleton, and endocrine organs.
• 🌸 Classical triad: café-au-lait spots, polyostotic fibrous dysplasia, endocrine dysfunction.
• 🎗️ Patients may have variable severity, with early childhood presentation.

🧬 Genetics

• Caused by activating somatic mutations in the GNAS gene.
• Leads to constitutive activation of Gsα protein and dysregulated cell signalling.
• Sporadic ➝ not inherited (mosaic distribution explains variable presentation).

⚙️ Aetiology

• Precocious puberty due to autonomous oestrogen release from ovarian cysts.
• Cushing’s syndrome from excess cortisol.
• Other endocrine hyperfunction: thyroid (thyrotoxicosis), pituitary (acromegaly), parathyroid (hypo/hyperparathyroidism).

🩺 Clinical Features

• 🌸 Precocious puberty (e.g. menstruation at age 2 in girls; rare testicular involvement in boys).
• 🦴 Polyostotic fibrous dysplasia ➝ bone deformity, pathological fractures, pain.
• ☕ Café-au-lait spots (irregular, “coast of Maine” borders; also seen in NF1 but with different pattern).
• ⚡ Endocrine abnormalities: thyrotoxicosis, Cushing’s, acromegaly, hypoparathyroidism.
• 🥴 Skeletal fragility and osteomalacia.

⚖️ Differential Diagnoses

• Neurofibromatosis type 1 (NF1)
• Other causes of precocious puberty
• Other causes of café-au-lait macules
• Skeletal dysplasias/fibrous dysplasia without endocrine features

🔬 Investigations

• Bloods: May show hypophosphataemia, low calcium, raised ALP.
• Endocrine tests: Cortisol, thyroid hormones, GH, sex steroids.
• Skeletal survey: To identify fibrous dysplasia lesions.
• Imaging: X-ray, MRI, or CT ➝ bone deformity and endocrine organ assessment.
• Genetic testing: Detection of GNAS mosaic mutations (specialist labs).

💊 Management

• 👩‍⚕️ Endocrinology review for hormonal excess (e.g. aromatase inhibitors for precocious puberty).
• 🦴 Orthopaedic input for deformities, fractures, or corrective surgery.
• 🧱 Bisphosphonates ➝ reduce bone pain and strengthen dysplastic bone.
• 🔧 Surgery for severe deformities or fracture fixation.
• 📅 Lifelong monitoring of endocrine function, skeletal health, and malignancy risk.
• 🤝 Psychosocial support for patient and family.

📈 Prognosis

• Most individuals can live a normal lifespan with multidisciplinary management.
• Severity varies depending on extent of bone disease and endocrine involvement.
• Early diagnosis and treatment of precocious puberty, fractures, and endocrine abnormalities improve outcomes.

✅ Conclusion

McCune-Albright Syndrome is a rare, sporadic, multisystem disorder due to somatic GNAS mutations. The triad of fibrous dysplasia, café-au-lait spots, and endocrine dysfunction is classical but variable. Early recognition, multidisciplinary management, and long-term follow-up are essential to optimise growth, development, and quality of life.

📚 References

• NIH – McCune-Albright Syndrome
• Mayo Clinic – MAS
• Medscape – MAS Overview
• NCBI – Pathophysiology & Clinical Features
• eMedicineHealth – MAS
• Rowe SM et al. (2001). McCune-Albright Syndrome. GeneReviews. Univ of Washington, Seattle.