McCune-Albright Syndrome

McCune-Albright Syndrome

McCune-Albright Syndrome (MAS) is a rare genetic disorder characterized by the triad of:

  • Polyostotic fibrous dysplasia of bone
  • Café-au-lait skin pigmentation
  • Autonomous endocrine hyperfunction

MAS is caused by a post-zygotic activating mutation in the GNAS gene, which encodes the alpha subunit of the stimulatory G protein. This mutation leads to constitutive activation of the Gsα protein, resulting in increased cAMP production and various clinical manifestations.

Key Clinical Features:

  1. Fibrous Dysplasia (FD):
    • Abnormal bone growth and weakness
    • Can affect single (monostotic) or multiple (polyostotic) bones
    • Common sites: long bones, ribs, skull base, and pelvis
    • Symptoms: pain, deformity, pathological fractures
  2. Café-au-lait Spots:
    • Large, irregular borders ("coast of Maine")
    • Often follow the midline of the body (Blaschko's lines)
    • Present at birth or appear in early infancy
  3. Endocrine Disorders:
    • Precocious puberty (most common)
    • Hyperthyroidism
    • Growth hormone excess
    • Cushing syndrome
    • Hypophosphatemic rickets

Other Associated Features:

  • Hepatobiliary dysfunction
  • Cardiac arrhythmias
  • Gastrointestinal polyps
  • Pancreatitis
  • Neurological complications (due to craniofacial FD)

Diagnostic Criteria:

Diagnosis is typically based on clinical features and confirmed by genetic testing.

Clinical Diagnosis:

  • Presence of at least two features of the classic triad
  • Careful physical examination and history

Imaging Studies:

  • X-rays: "ground-glass" appearance of fibrous dysplasia
  • Bone scintigraphy: extent of skeletal involvement
  • CT and MRI: detailed evaluation of affected bones

Laboratory Tests:

  • Endocrine function tests (e.g., thyroid, growth hormone, cortisol)
  • Serum calcium, phosphate, and alkaline phosphatase levels

Genetic Testing:

  • Detection of activating mutations in the GNAS gene
  • Often requires testing of affected tissues due to mosaicism

Treatment Approach:

Management of MAS is multidisciplinary and focuses on treating individual manifestations:

1. Fibrous Dysplasia:

  • Bisphosphonates to reduce bone pain and improve bone density
  • Orthopedic interventions for fractures or severe deformities
  • Physical therapy and rehabilitation

2. Endocrine Disorders:

  • Precocious puberty: GnRH analogs, aromatase inhibitors
  • Hyperthyroidism: Antithyroid drugs, radioactive iodine, or surgery
  • Growth hormone excess: Somatostatin analogs, GH receptor antagonists
  • Cushing syndrome: Adrenalectomy if unilateral

3. Café-au-lait Spots:

  • Usually do not require treatment
  • Cosmetic interventions if desired (e.g., laser therapy)

4. Other Manifestations:

  • Regular screening for associated complications
  • Targeted interventions as needed (e.g., hepatobiliary issues, cardiac arrhythmias)

Long-term Outlook:

  • Highly variable, depending on the extent and severity of involvement
  • FD lesions typically stabilize after puberty but may progress in adulthood
  • Endocrine manifestations often require lifelong management
  • Regular follow-up is essential to monitor for progression and complications

Challenges:

  • Pain management in severe FD
  • Psychosocial impact of chronic illness and physical differences
  • Risk of malignant transformation in FD lesions (rare but reported)


Further Reading
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