Mazabraud Syndrome

Fibromyxomas in fibrous dysplasia; combined soft tissue and skeletal hamartomatous disorder.

Mazabraud syndrome is a rare benign condition characterized by the co-occurrence of intramuscular myxomas and monostotic or polyostotic fibrous dysplasia of bone. It represents a non-inflammatory, hamartomatous disorder involving mesenchymal tissue affecting both bone and soft tissue.

Extremely rare (<1:1,000,000). More common in women (F:M ≈ 2–3:1). Bone lesions typically develop during childhood, whereas intramuscular myxomas usually manifest in adulthood (3rd to 5th decade).

Belongs to the group of hamartomatous syndromes involving the skeletal and soft tissues. Considered part of the GNAS-associated mosaic disorders.

In over 80% of cases, identical postzygotic GNAS1 mutations are found in both bone and soft tissue lesions, suggesting a clonal origin. These mutations lead to constitutive activation of the Gs-alpha subunit, increased intracellular cAMP, and stimulation of mesenchymal cell proliferation.

• Bone: fibrous dysplasia (mono- or polyostotic) presenting with pain, deformities, and increased fracture risk
• Soft tissue: intramuscular myxomas, often multiple, soft, painless, slow-growing
• 80% of cases present with ipsilateral distribution of myxomas and bone lesions
• Unlike McCune-Albright syndrome, endocrine abnormalities are typically absent

• Clinical: combination of fibrous dysplasia and soft tissue tumors
• Imaging:
  • CT/MRI/X-ray: fibrous dysplasia shows “ground-glass” matrix; myxomas appear as hypodense or high T2-signal lesions
• Histology:
  • Fibrous dysplasia: fibro-osseous lesions with irregular trabeculae in fibrous stroma
  • Myxomas: sparsely cellular myxoid matrix with spindle-shaped cells
• Genetics: detection of GNAS1 mutation (e.g., p.R201H or p.R201C)

• Fibrous dysplasia: pelvis, femur, tibia, ribs, craniofacial bones
• Intramuscular myxomas: commonly in thighs, buttocks, shoulder girdle; may affect multiple regions

Longstanding, painless bony swelling or deformity since childhood, followed in adulthood by slowly enlarging soft tissue nodules. Endocrine symptoms are typically absent.

Not relevant. No cutaneous manifestations are associated.

• Increased risk of pathological fractures
• Rare malignant transformation of fibrous dysplasia (e.g., osteosarcoma)
• Very rare malignant progression of intramuscular myxomas

Benign and chronic course. Malignant transformation is rare (<1–2%). Long-term monitoring is advised.

No preventive measures. Early detection through imaging of atypical soft tissue masses is essential.

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