Best practice management guidelines for fibrous dysplasia/McCune-Albright syndrome: a consensus statement from the FD/MAS international consortium

Abstract

Fibrous Dysplasia / McCune Albright syndrome (FD/MAS) represents a wide spectrum of diseases due to somatic gain-of-function mutations of the GNAS gene. The mutation leads to overactivity in the target tissues and to a wide phenotype of clinical features that vary in severity and age of onset. The rarity of the disease and its variable presentation to multiple specialities often leads to misdiagnosis and inappropriate variability in investigations and treatments. To address this, our international consortium of clinicians, researchers, and patients' advocates has developed pragmatic clinical guidelines for best clinical practice for the definition, diagnosis, staging, treatment and monitoring for FD/MAS to empower patients and support clinical teams in both general and specialised healthcare settings. With the lack of strong evidence to inform care, the guidelines were developed based on review of published literature, long-standing extensive experience of authors, input from other healthcare professionals involved in the care of FD/MAS patients and feedback from patients and patient groups across the globe. This has led to the formulation of a set of statements to inform healthcare professionals, patients, their families, carers and patient groups of the best practice of care. It is anticipated the implementation of these recommendations will lead to improvement in the care of patients with FD/MAS internationally.

Keywords: Diagnosis; Fibrous dysplasia; Guidelines; Management; McCune Albright syndrome.

Fig. 1

Representative images of café-au-lait macules in patients with McCune-Albright syndrome. Photographs of the shoulder (a), back (b), and legs (c) from three patients demonstrating characteristic hyperpigmented lesions with jagged borders, and tendency to either occur or reflect around (“respect”) the midline of the body. Images A and C show large lesions, while the patient in image B has two small lesions in a classic location, demonstrating the broad potential spectrum of involvement

Fig. 2

Representative radiographic features of endocrine involvement in McCune-Albright syndrome. a Pelvic ultrasonography in a 5-year-old girl with clinical signs of precocious puberty demonstrating a large unilateral ovarian cyst. b Testicular ultrasonography in a patient with macro-orchidism demonstrating a discrete, mixed hyper- and hypoechoic lesion (red arrowheads). c Thyroid ultrasonography showing diffuse, bilateral involvement with multiple hyper- and hypoechoic nodules. d A pituitary MRI in a patient with growth hormone excess revealing a pituitary macroadenoma (red arrow) and fibrous dysplasia involvement throughout the skull base (white star)

Fig. 3

Representative radiographic features of fibrous dysplasia. a Femoral X-ray demonstrating diffuse involvement with fibrous dysplasia and a coxa vara (“shepherd’s crook”) deformity (red arrow). Note the irregular appearance of the distal femoral metaphyses (yellow arrowhead) resulting from FGF-23-mediated rickets. b Humeral X-ray demonstrating characteristic features of fibrous dysplasia, including homogenous “ground glass” appearance and cortical thinning. Bowing has occurred at a previously fractured site in the midshaft (red arrowhead). c X-ray from a patient with diffuse spinal FD and resulting thoraco-lumbar scoliosis. Note the presence of bilateral intramedullary femoral rods. d Technetium-99 scintigraphy scan showing increased tracer uptake in areas of fibrous dysplasia, including the skull, spine, right humerus, and right lower extremity (red arrowheads). Diffuse bilateral tracer uptake is also observed in the epiphyses of this growing adolescent. e T2-weight magnetic resonance imaging of the lower extremities showing well-demarcated lesions of intermediate to high signal intensity in the bilateral femurs (red arrows), corresponding to fibrous dysplasia lesions. f Computed tomography of the skull showing diffuse homogenous, “ground glass” involvement characteristic of craniofacial fibrous dysplasia. The bilateral optic canals are involved with fibrous dysplasia and widely patent (red arrows)