Fibrous dysplasia/McCune-Albright syndrome

Disease definition

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS; OMIM#174800)


The exact prevalence of fibrous dysplasia is unknown, but it is less than 1:2000.

Clinical description

FD/MAS is a rare disorder characterized by skeletal lesions, skin hyperpigmentation, and hyper-functioning endocrinopathies


It arises from post-zygotic gain-of-function mutations in the GNAS gene, which encodes the α-subunit of the Gs signalling protein. These mutations disrupt the intrinsic GTPase activity of Gsα, leading to persistent stimulation of adenylyl cyclase and dysregulated production of cyclic AMP and downstream signalling. The resulting disease is mosaic with a broad clinical spectrum, ranging from a trivial incidentally discovered radiographic finding to severe and disabling disease.

Diagnostic methods

A diagnosis of the subtypes of FD/MAS can only be made after a thorough evaluation of a) the extent of skeletal disease: monostotic/polyostotic and b) the presence of extra-skeletal manifestations. Monostotic fibrous dysplasia is defined as the presence of fibrous dysplasia in one skeletal site only. Polyostotic fibrous dysplasia is defined as the presence of fibrous dysplasia in more than one skeletal site without extra-skeletal manifestations. McCune-Albright syndrome is defined as the combination of FD and one or more extra-skeletal feature, OR the presence of two or more extra skeletal features. Not requiring FD for the diagnosis of MAS reflects better understanding of the molecular pathogenesis of the disorder. Mazabraud Syndrome is the combination of FD with intramuscular myxoma(s). The myxoma is defined as an extra-skeletal manifestation of FD/MAS and may occur in association with any type of the disease (monostotic, polyostotic or MAS).  Other extra-skeletal features include:

  1. Café-au-lait skin macules with characteristic features of jagged, irregular borders (Coast of Maine) and a distribution showing the so-called “respect of” the midline of the body
  2. Gonadotropin-independent sex steroid production resulting in precocious puberty, recurrent ovarian cysts in girls and women or autonomous testosterone production in boys and men. This includes testicular lesions consistent with FD/MAS with or without associated gonadotropin-independent precocious puberty.
  3. Thyroid lesions consistent with FD/MAS with or without non-autoimmune hyperthyroidism
  4. Growth hormone excess
  5. Neonatal hypercortisolism

Of note, FGF-23-associated hypophophataemia is not considered a feature of MAS but rather a marker of the severity of skeletal FD.

Differential diagnosis


Antenatal diagnosis

Not applicable.

Genetic counseling

While a genetic disease, the mutation occurs after fertilization and so can not be inherited.

Management and treatment

Management consists of general measures (Provision of information about the disease, Lifestyle advice, Exercise and rehabilitation) and specific measures including management of FGF-23 induced renal phosphate wasting, Scoliosis, bone pain, Mazabraud syndrome, endocrinopathies of the ovary, testes, thyroid, pituitary and adrenals, haematological manifestations, gastrointestinal manifestations and increased risk of malignancy. Surgical management includes orthopaedic, spinal, craniofacial, maxillofacial and dental aspects.


Very variable depending on severity and response to drug and surgical treatment.

For patients

– Seek a specialist who has experience in treating people with Fibrous dysplasia/McCune-Albright syndrome. You are not alone as a person with FD/MAS or a parent or carer.
– Do connect with patients groups in Fibrous dysplasia/McCune-Albright syndrome – start at the Fibrous Dysplasia Foundation or search Facebook or social media.

– Lose hope, there is usually something that can be done to help you.
– Don’t be put off by doctors who say there is nothing that can be done.
– Ask to see a specialist and use your patient groups.

Expert reviewer

MK Javaid

Font link

Javaid MK et al., Best practice management guidelines for fibrous dysplasia/McCune-Albright syndrome: a consensus statement from the FD/MAS international consortium. Orphanet J Rare Dis. 2019 Jun 13;14(1):139. doi: 10.1186/s13023-019-1102-9.