constitutively activating Gsα mutations present with fibrous dysplasia alone, affecting either a single bone or multiple bones. In patients with isolated fibrous dysplasia, histological changes appear to be indistinguishable form those seen in the context of MAS [110, 111]. As in patients with MAS, nearly all isolated cases of fibrous dysplasia are associated with GNAS mutations at Arg201; however, a study using a mutation-specific restriction enzyme digest assay has recently identified three Gln227 (to Leu) mutations among a total of 56 samples [112]. The skin lesions, which typically have irregular borders, can be single or multiple light brown hyperpigmented areas arranged in segmental patterns that follow the developmental lines of Blaschko [106, 109]. Endocrine abnormalities, in addition to precocious puberty, can be summarized as hyperplasia and increased function of many different glands, including thyroid, adrenal, and pituitary [113-115]. Some patients with MAS also exhibit urinary phosphate wasting, hypophosphatemia, and bone mineralization defects observed as rickets or osteomalacia [113, 114]. While the latter findings are consistent with the role of Gsα in mediating the phosphaturic actions of parathyroid hormone in the renal proximal tubule, recent data shows that serum phosphate in MAS patients is negatively correlated with the level of fibroblast
