What is Fibrous Dysplasia?


"Fibrous dysplasia (FD) is an uncommon bone disease that can affect any bone in the body. The severity of the disease covers a wide spectrum. It can affect a single bone and go unnoticed for years, or it can affect virtually every bone, start very early in life, and result in significant physical impairment.

It is caused by defective gene in the cells that form bone called Gsa. It is encoded in the genome by the gene GNAS. This mutation occurs sometime during development of a baby while it is still in the mother’s uterus. If the mutation occurs early in development, many tissues may be affected. If it occurs late in development, very few tissues may have the mutation. Because the mutation occurs before birth, MAS is considered a genetic disease. But unlike almost all other diseases it is not hereditary because it cannot exist in sperm or egg cells. When the long bones (the bones of the legs and arms) or flat bones (ribs, spine and pelvis) are affected, the bones weaken, may bow, may be painful, and will frequently fracture. Affected bones in the skull often expand, may cause disfigurement and, again, are may be painful.

The areas of the skeleton that are affected are probably established early in life (often long before the disease is even detected). Once the affected areas are established, it is uncommon for new areas to be affected. Affected areas may increase in size or severity, but in general most of the problems as far as fractures and expansion have occurred by the age of 15. Once a bone is affected, it never returns to normal. Pain is commonly associated with FD.  It is often not present in childhood, usually starts later in the course of the disease, and if present, usually continues.

FD can be associated with birth marks (cafe-au-lait spots), and a number of endocrine problems such as precocious puberty, hyperthyroidism, low blood phosphorus, excess growth hormone, and very rarely neonatal Cushings disease. When one or more features are present, this is known as McCune-Albright syndrome. The birth marks can often be the first sign of the disease. However, almost any combination can occur. For example, severe bone disease (with or without endocrine problems) can be associated with minimal skin disease, and vice versa.

FD is typically visible on X-rays. A bone scan involving the use of a radioactive tracer that is taken up by bone is the most sensitive tool for detecting FD lesions, and are often useful at the initial evaluation, for determining the extent of the disease. FD has a typical appearance on radiographs described as “ground glass”. In general, in the long bones, these lesions have a “lytic” appearance. The lesions usually arise in the medullary cavity (middle part of the bone) and expand outward replacing normal bone with the result of thinning of the cortex (outer part of the bone). It is possible for any bone to be involved, but the proximal femur (top part) is the site most commonly involved. The bones are “soft” and prone to deformation, with the classical lesion being the “shepherd’s crook” deformity of the proximal femur (bowing).

There is no cure for FD, but there are treatments for the various problems associated with it. Surgery remains the mainstay of treatment for the bone disease. Surgical treatment is complicated and is best performed by surgeons with experience with FD. Medications known as bisphosphonates (pamidronate (Aredia), zoledronate (Zometa), etc.) have been shown to be very effective in relieving pain. In general, surgery in the bones of the skull usually is not medically required. Although the nerves to the eyes and ears are often surrounded by FD, blindness and significant hearing loss are uncommon."

-Fibrous Dysplasia Foundation

https://www.fibrousdysplasia.org/


What is McCune-Albright Syndrome?


"Originally, the McCune-Albright syndrome (MAS) was defined by the triad of polyostotic fibrous dysplasia of bone (FD), café-au-lait skin pigmentation, and precocious puberty (PP). Later, it was recognized that other endocrinopathies, including hyperthyroidism, growth hormone excess, renal phosphate wasting, with or without rickets in children or osteomalacia in adults, and Cushing syndrome, could be found in association with the original triad. Rarely, other organ systems may be involved (liver, cardiac, parathyroid, pancreas).

While MAS is rare, fibrous dysplasia (FD) is not. FD can involve a single skeletal site (monostotic FD, MFD), or multiple sites (polyostotic FD, PFD). Very rarely one can find PP in association with café-au-lait skin pigmentation in the absence of FD (1%), but in general, FD seems to be the component of the clinical diagnosis most commonly present. Therefore, a more clinically relevant definition of MAS, broader than the original triad of FD + PP + café-au-lait is: MAS = FD + (at least one of the typical hyperfunctioning endocrinopathies and/or café-au-lait spots), almost any combination is possible.

The disease is caused by mutations in the a protein that regulates cell action known as Gsa. It is encoded in the genome by the gene GNAS. The fact that the disease has never been passed from parent to child has led to the notion that the disease is the result of mutations that occur after fertilization, at a point early in the development of the embryo or fetus. The earlier in development the mutation occurs, the greater the disease tissue burden.

Typically, the signs and symptoms of either PP or FD usually account for the initial presentation. In girls with PP, it is usually vaginal bleeding or spotting, accompanied by development of breast tissue, with little or no pubic hair. In boys, it can be bilateral (or unilateral) testicular enlargement with penile enlargement, scrotal skin thickening, body odor, pubic and axiallary hair, and precocious sexual behavior.

FD in the axial skeleton usually presents with a limp and/or pain (sometimes reported by children as being "tired"), but occasionally a pathologic fracture may be the presenting sign. The x-ray will demonstrate a typical lesion arising in the middle of the bone cavity with a "ground glass" appearance. Alternatively, FD in the craniofacial bones will usually present as a painless "lump" or facial asymmetry. The areas most commonly involved are the proximal femora and skull base. In retrospect, café-au-lait spots are the most common but unappreciated "presenting" sign, usually present at birth or shortly thereafter.

Diagnosis of MAS is established on clinical grounds. X-rays are often sufficient to make the diagnosis of FD. A bone scan involving the use of a radioactive tracer that is taken up by bone is the most sensitive tool for detecting the presence of FD lesions, and are often useful, especially at the initial evaluation, for determining the extent of the disease. FD has a typical appearance on radiographs described as "ground glass". In general, in the long bones, these lesions have a "lytic" appearance. The lesions usually arise in the medullary cavity (middle part of the bone) and expand outward replacing normal bone with the result of thinning of the cortex (outer part of the bone). It is possible for any bone to be involved, but the proximal femur (top part) is the site most commonly involved. The bones are "soft" and prone to deformation, with the classical lesion being the "shepherd's crook" deformity of the proximal femur (bowing)."

-Fibrous Dysplasia Foundation

​https://www.fibrousdysplasia.org/