Current approach to fibrous dysplasia of bone and McCune–Albright syndrome

Abstract

Fibrous dysplasia (FD) of bone is an uncommon disease caused by sporadic, congenital mutations in the cAMP regulating protein, Gsα. It is an example of somatic mosaicism in which a wide spectrum of disease is possible. Widespread skeletal involvement is often associated with varying combinations of café-au-lait skin spots, and/or endocrine dysfunction (precocious puberty, renal phosphate wasting, hyperthyroidism, and/or growth hormone excess). Unrecognized and untreated endocrine dysfunction can exacerbate the skeletal disease. The diagnosis is usually established on clinical grounds on the basis of physical examination and typical radiographic appearance. Occasionally, gene testing of affected tissue may be helpful. The skeletal sites involved with disease are established at an early age, and the complications of fracture deformity are most pronounced in childhood. Bone pain in the absence of a fracture is more common in adults, but can also be present in children. Treatment with bisphosphonates is usually effective at relieving pain, but probably has no effect on the natural history of the disease. Scoliosis, which was previously thought to be an uncommon occurrence, has been shown to be common and progressive, and as such, warrants investigation and, when necessary, surgical treatment. The surgical management of FD remains challenging. Timing and technique remain controversial, but some consensus exists in that grafting materials (of any type) usually fail and should not be a central aspect of the surgical approach. Intramedullary devices are in general superior to side plates and screws. In extremely widespread disease with very early fracture and deformity, no surgical approach will affect final functional outcome. Efforts should be made for the initiation of international collaborative studies to better define optimal surgical approaches to the treatment of this challenging disease.

McCune-Albright Syndrome Mimicking Malignancy: an Endocrine Disease From Oncologist’s Perspective

“…The plain film reveals a lytic, ground glass lesion in FD. In case of doubt about the diagnosis, the CT is helpful in demonstrating the medullary-based, fibro-osseous nature of FD (1). After the diagnosis of FD, bone scintigraphy or a skeletal survey should be done to determine the extent of the disease.…”

“…It comprises around 7-10% of all benign bone tumors. 70-80% of FD cases are monostotic and 20-30% are polyostotic (1). McCune-Albright syndrome (MAS) is defined by the triad of FD, café au lait spots, and precocious puberty or at least one of the typical hyperfunctioning endocrinopathies in almost any possible combination (2).…”

Sarcomatous transformation in the McCune–Albright syndrome

“…According to the genetic literature, it is a syndrome with a variable spectrum, and the absence of vertical transmission suggests that the mutation is somatic or postzygotic, probably occurring before the development of the trilaminar disk, from ecto, end and mesodermal tissues. The mutation occurs in the gene GNAS1, with substitution of arginine residue (codon 201) and glycine (codon 227) in exons 8 and 9, respectively, thus resulting in autonomous hyperfunction in the adenylate cyclase system of the affected tissues [1,5].…”

“…However, the symptoms are variable, depending on the affected area and the extent of the injuries. Since the bone deformities most frequently involve the face and skull, esthetics becomes a major limiting factor, with psychological distress for both patients and their families [1,5,6].…”

“…The monostotic form, which occurs more frequently, affects a single bone or contiguous bones and usually has an asymptomatic course, while the polyostotic pattern is characterized by involvement of several bones. When the latter occurs in patients with café-au-lait spots and endocrine disorders, it characterizes McCune-Albright syndrome [1,2].…”