McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia

Abstract

Fibrous dysplasia (FD) is sometimes accompanied by extraskeletal manifestations that can include any combination of café-au-lait macules, hyperfunctioning endocrinopathies, such as gonadotropin-independent precocious puberty, hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting, and/or Cushing syndrome, as well as other less common features. The combination of any of these findings, with or without FD, is known as McCune-Albright syndrome (MAS). The broad spectrum of involved tissues and the unpredictable combination of findings owe to the fact that molecular defect is due to dominant activating mutations in the widely expressed signaling protein, Gsα, and the fact these mutations arises sporadically, often times early in development, prior to gastrulation, and can distribute across many or few tissues.The complexity can be mastered by a systematic screening of potentially involved tissues and cognizance that the pattern of involved tissues is established, to some degree, in utero. Thorough testing allows the clinician to establish, often times at presentation, the full extent of the disease, and importantly as well what tissues are unaffected. Treatment and follow-up can then be focused on affected systems and a meaningful prognosis can be offered to the patient and family. The authors outline screening and treatment strategies that allow for effective management of the extraskeletal manifestations of FD.

Сushing’s syndrome in early infancy due to МcCune—Albright syndrome

“…Следует отметить, что фиброзно-кистозная дис-плазия, встречающаяся в 98% случаев СМОБ [6], имеет, как правило, распространенный характер. В нашем случае, очаги поражения, помимо черепа, наблюдались и в других костях скелета.…”

“…АКТГ-независимый гиперкортицизм встречает-ся в 4-5% случаев СМОБ [6] и связан с двусторон-ней нодулярной пигментной гиперплазией надпо-чечников. Чаще всего признаки гиперкортицизма при СМОБ возникают в первые месяцы жизни и могут быть первыми проявлениями заболевания.…”

Wnts’ fashion statement: from body stature to dysplasia

“…The bone lesions may be associated with endocrine dysfunction and skin spots, known as the McCune-Albright syndrome. 58 A recent article from our lab demonstrated a causative role of the Wnt/b-catenin pathway upregulation due to gain-of-function mutation in GNAS, in the pathology of fibrous dysplasia. 59 …”

Locally Aggressive Fibrous Dysplasia Mimicking Malignancy: A Report of Four Cases and Review of the Literature

“…Sudden appearance of pain associated with swelling in a patient with fibrous dysplasia usually indicates either pathologic fracture or in rare instances malignant transformation [11]. Radiographically, malignant transformation is associated with cortical destruction and an adjacent soft tissue mass [2]. These features also are observed in primary bone sarcomas and metastatic lesions.…”

“…Case Descriptions We report four unusual cases of fibrous dysplasia with an aggressive radiographic appearance. They occurred in the rib (1), ilium (2), and distal femur (1). Two patients had pain and two had swelling.…”