Dumitrescu Claudia E, Collins Michael T
Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
Orphanet J Rare Dis. 2008 May 19;3:12. doi: 10.1186/1750-1172-3-12.
McCune-Albright syndrome (MAS) is classically defined by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP). It is a rare disease with estimated prevalence between 1/100,000 and 1/1,000,000. FD can involve a single or multiple skeletal sites and presents with a limp and/or pain, and, occasionally, a pathologic fracture. Scoliosis is common and may be progressive. In addition to PP (vaginal bleeding or spotting and development of breast tissue in girls, testicular and penile enlargement and precocious sexual behavior in boys), other hyperfunctioning endocrinopathies may be involved including hyperthyroidism, growth hormone excess, Cushing syndrome, and renal phosphate wasting. Café-au-lait spots usually appear in the neonatal period, but it is most often PP or FD that brings the child to medical attention. Renal involvement is seen in approximately 50% of the patients with MAS. The disease results from somatic mutations of the GNAS gene, specifically mutations in the cAMP regulating protein, Gs alpha. The extent of the disease is determined by the proliferation, migration and survival of the cell in which the mutation spontaneously occurs during embryonic development. Diagnosis of MAS is usually established on clinical grounds. Plain radiographs are often sufficient to make the diagnosis of FD and biopsy of FD lesions can confirm the diagnosis. The evaluation of patients with MAS should be guided by knowledge of the spectrum of tissues that may be involved, with specific testing for each. Genetic testing is possible, but is not routinely available. Genetic counseling, however, should be offered. Differential diagnoses include neurofibromatosis, osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty, and ovarian neoplasm. Treatment is dictated by the tissues affected, and the extent to which they are affected. Generally, some form of surgical intervention is recommended. Bisphosphonates are frequently used in the treatment of FD. Strengthening exercises are recommended to help maintaining the musculature around the FD bone and minimize the risk for fracture. Treatment of all endocrinopathies is required. Malignancies associated with MAS are distinctly rare occurrences. Malignant transformation of FD lesions occurs in probably less than 1% of the cases of MAS.
McCune - Albright综合征（MAS）的经典定义是由骨纤维发育不良（FD）、咖啡斑皮肤斑点和性早熟（PP）这一临床三联征构成。它是一种罕见疾病，估计患病率在1/100,000至1/1,000,000之间。FD可累及单个或多个骨骼部位，表现为跛行和/或疼痛，偶尔还会发生病理性骨折。脊柱侧弯很常见，且可能会进展。除了性早熟（女孩出现阴道出血或点滴出血以及乳腺组织发育，男孩出现睾丸和阴茎增大以及性早熟行为）外，其他功能亢进性内分泌疾病也可能累及，包括甲状腺功能亢进、生长激素过多、库欣综合征和肾性磷酸盐耗竭。咖啡斑通常在新生儿期出现，但最常是性早熟或骨纤维发育不良使患儿就医。约50%的MAS患者会出现肾脏受累。该疾病由GNAS基因的体细胞突变导致，具体是环磷酸腺苷调节蛋白Gsα中的突变。疾病的严重程度取决于胚胎发育过程中自发发生突变的细胞的增殖、迁移和存活情况。MAS的诊断通常基于临床依据。普通X线平片通常足以诊断FD，FD病变的活检可以确诊。对MAS患者的评估应以可能受累组织范围的知识为指导，并针对每种组织进行特定检测。基因检测可行，但并非常规可用。不过，应提供遗传咨询。鉴别诊断包括神经纤维瘤病、骨化性纤维发育不良、非骨化性纤维瘤、特发性中枢性性早熟和卵巢肿瘤。治疗取决于受影响的组织及其受影响的程度。一般来说，建议采取某种形式的手术干预。双膦酸盐常用于治疗FD。建议进行强化锻炼，以帮助维持FD骨骼周围的肌肉组织并将骨折风险降至最低。所有内分泌疾病都需要治疗。与MAS相关的恶性肿瘤极为罕见。FD病变的恶性转化在MAS病例中可能不到1%。
