56 McCune-Albright Syndrome
Polyostotic fibrous dysplasia, PFD or POFD
Multiple areas of cutaneous light brown pigmenta- tion, polyostotic fibrous dysplasia of bones, hyper- function of one or more endocrine glands (especially gonads and thyroid), facial asymmetry
Frequency: Rare (fewer than 100 published cases).
Genetics
Virtually all cases sporadic; autosomal dominant (OMIM 174800), due to mutations in the GNAS1 gene encoding the alpha subunit of the stimulatory G-pro- tein of adenylyl cyclase, mapped to 20q13.2; a lethal gene compatible with viability only in the mosaic state (highly variable abnormality); allelic to pseudo- hypoparathyroidism type 1A (OMIM 103580) (re- duced function); mutation in GNAS1 also found in growth hormone-secreting pituitary tumors and thyroid tumors.
Clinical Features
• Patchy/streaky skin hyperpigmentation with irregular margins
• Facial asymmetry (25%)
• Pigmentation of oral mucosa and lips
• Precocious puberty, hyperthyroidism, hyper- parathyroidism, Cushing syndrome, gigantism, acromegaly, toxic goiter, hyperprolactinemia, gynecomastia
• Leg pain, lower limb deformity, bowing of legs, pathologic fractures
• Scoliosis
• Osteosarcomatous transformation
• Visual loss from optic nerve encroachment
• Deafness
Differential Diagnosis
• Fibrous dysplasia
• Jaffe-Campanacci syndrome
• Neurofibromatosis
Radiographic Features Generalized Bone Defects
• Polyostotic (more than one bone involved) fibrous dysplasia (patchy rarefaction and sclerotic le- sions)
• Replacement of normal bone with abnormal fi- brous tissue, with loss of the trabecular pattern (ground-glass appearance)
• Pathologic fractures
• Pseudarthrosis
• Bone deformities
• Advanced bone age
• Tendency to asymmetry
• Hypophosphatemic osteomalacia (rickets)
McCune-Albright Syndrome 744
Fig. 56.1. Patient 1, age 6 years.
Note multiple, irregular café- au-lait skin pigmentation areas over neck and upper back. (Re- printed, with permission, from Canepa et al. 1996)
Skull
• Unilaterally distributed areas of thickening, alter- nating with cyst-like lesions in cranial bones
• Increased density of skull base and facial bones
• Obliteration of paranasal sinuses Limbs
• Lacunar, cyst-like radiolucencies and/or opaque lesions in shafts of tubular bones (proximal femur most frequently involved, followed by tibia, fibula, humerus, radius, and ulna)
• Widened shaft of long bones, thin cortices
• Long bone deformities (shepherd’s crook defor- mity of proximal femur)
Chest
• Sclerotic lesions of ribs
• Fibrotic lesions of scapulae Pelvis
• Fibrotic lesions of pelvis
McCune-Albright Syndrome 745
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Fig. 56.2. aPatient 2, age 13 years. Dense, thick bone at base of skull and frontal bones. b Patient 3, age 19 years. Extensive substi- tution of normal bone by a mixture of lytic and sclerotic lesions, resulting in ‘cotton-wool’ or ‘pagetoid’ appearance of skull
a b
Fig. 56.3. aPatient 4, adult. b Patient 5, age 18 years; note multiple lucent expansile lesions, interspersed with sclerotic areas, involving several posterior ribs in a and a single rib at the costovertebral junction in b
a b
Bibliography
Alvarez-Arratia MC, Rivas F, Avila-Abundis A, Hernandez A, Nazara Z, Lopez A, Castillo A, Cantu JM. A probable mono- genic form of polyostotic fibrous dysplasia. Clin Genet 1983; 24: 132–9
Canepa G, Maroteaux P, Pietrogrande V. Sindromi dismorfiche e malattie costituzionali dello scheletro. Piccin, Padova, 1996
Firat D, Stutzman L. Fibrous dysplasia of the bone: review of twenty-four cases. Am J Med 1968; 44: 421–9
Hibbs RE, Rush HP. Albright’s syndrome. Ann Intern Med 1952; 37: 587–93
Inamo Y, Hanawa Y, Kin H, Okuni M. Findings on magnetic resonance imaging of the spine and femur in a case of McCune-Albright syndrome. Pediatr Radiol 1993; 23: 15–8 Kairemo KJ, Verho S, Dunkel L. Imaging of McCune-Albright
syndrome using bone single photon emission computed tomography. Eur J Pediatr 1999; 158: 123–6
Kitoh H, Nogami H. A simple bone cyst containing secretory cells in its lining membrane in a patient with polyostotic fibrous dysplasia. Pediatr Radiol 1999; 29: 481–3
Ozaki T, Sugihara M, Nakatsuka Y, Kawai A, Inoue H. Polyostot- ic fibrous dysplasia. A long-term follow up of 8 patients. Int Orthop 1996; 20: 227–32
Schwindinger WF, Francomano CA, Levine MA. Identification of a mutation in the gene encoding for the alpha subunit of the stimulatory G-protein of adenylyl cyclase in McCune- Albright syndrome. Proc Natl Acad Sci USA 1992; 89:
5152–6
Viljoen DL, Versfeld GA, Losken W, Beighton P. Polyostotic fibrous dysplasia with cranial hyperostosis: new entity or most severe form of polyostotic fibrous dysplasia? Am J Med Genet 1988; 29: 661–7
McCune-Albright Syndrome 746
Fig. 56.4.Patient 3, age 19 years.
Massive replacement of normal bone by fibrous tissue, character- ized radiographically by lucent, cyst-like, expansile lesions. The cortices are strikingly thinned.
Fig. 56.5. Patient 3, age 19 years. Virtually all bones are in- volved by fibrous dysplasia, resulting in a lucent, hazy appear- ance alternating with small areas of sclerosis. Note severe bow- ing of tibia and fibula. Also note that cortices are extremely thinned, but not violated
McCune-Albright Syndrome 747
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Fig. 56.6. Different degrees of humeral involvement in a patient 6 (age 22 years), b patient 7 (adult), and c patient 3 (19 years)
a c
b
Fig. 56.7 a, b. Localized radiolucent lesions with endosteal scalloping are seen in carpal bones, metacarpals, and finger and toe phalanges in a patient 6 (age 22 years) and b patient 1 (age 6 years). (Reprinted, with permission, from Canepa et al. 1996)
a b
