Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Surgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
J Bone Miner Res. 2018 Nov;33(11):1990-1998. doi: 10.1002/jbmr.3531. Epub 2018 Aug 3.
Fibrous dysplasia (FD) is a mosaic disorder of benign fibro-osseous lesions, which may be associated with extraskeletal features as part of McCune-Albright syndrome (MAS). Cranial base abnormalities, including Chiari I malformation (CM1), in which the cerebellum extends below the foramen magnum, and secondary basilar invagination (BI), in which the odontoid prolapses into the posterior cranial fossa, are potentially serious complications of metabolic bone disorders. The purpose of this study was to determine the prevalence, natural history, and risk factors for CM1 and BI in patients with FD/MAS, and to determine mechanisms of cranial base deformities. Clinical and radiographic data from subjects in an FD/MAS natural history study were evaluated and compared to normal controls. In 158 patients with craniofacial FD, 10 (6.3%) cases of CM1 and 12 (7.6%) cases of BI were diagnosed. No cranial base abnormalities were identified in 10 control subjects. Craniomorphometric and volumetric analyses identified cranial constriction and cranial settling as the primary mechanisms of cranial base abnormalities, whereas intracranial hypertension was a contributing factor in a minority of subjects. Longitudinal analyses found progression of odontoid position with age, but no progression of tonsillar position. No endocrinopathies were associated with CM1. MAS endocrinopathies associated with BI included hyperthyroidism (odds ratio [OR] 12.0; 95% confidence interval [CI], 2.9 to 55.6; p < 0.01), precocious puberty (OR 5.6; 95% CI, 1.2 to 26.0; p < 0.05), and hypophosphatemia (OR 7.7; 95% CI, 1.9 to 27.0; p < 0.01). Scoliosis was associated with both CM1 (OR 4.8; 95% CI, 1.1 to 22.8; p < 0.05) and BI (OR = infinity; 95% CI, 4.7 to infinity; p < 0.01). This study successfully characterized cranial base abnormalities in FD/MAS and the pathophysiological connection between them. These findings support routine screening for cranial base abnormalities in patients with craniofacial FD, as well as aggressive management of contributory risk factors. © 2018 American Society for Bone and Mineral Research.
纤维发育不良 (FD) 是一种良性纤维骨性病变的镶嵌障碍，可能与 extraskeletal 特征相关，作为 McCune-Albright 综合征 (MAS) 的一部分。颅底异常，包括 Chiari I 畸形 (CM1)，其中小脑延伸至枕骨大孔以下，以及继发性基底凹陷 (BI)，其中齿状突突入颅后窝，是代谢性骨疾病的潜在严重并发症。本研究的目的是确定 FD/MAS 患者中 CM1 和 BI 的患病率、自然史和危险因素，并确定颅底畸形的发病机制。对 FD/MAS 自然史研究中的受试者的临床和影像学数据进行了评估，并与正常对照组进行了比较。在 158 例颅面 FD 患者中，诊断出 10 例 (6.3%) CM1 和 12 例 (7.6%) BI。在 10 名对照受试者中未发现颅底异常。颅形态计量学和体积分析确定颅狭窄和颅沉降为颅底异常的主要机制，而颅内压升高在少数受试者中是一个促成因素。纵向分析发现齿状突位置随年龄而进展，但扁桃体位置无进展。无内分泌疾病与 CM1 相关。与 BI 相关的 MAS 内分泌疾病包括甲状腺功能亢进症 (比值比 [OR] 12.0；95%置信区间 [CI]，2.9 至 55.6；p<0.01)、性早熟 (OR 5.6；95%CI，1.2 至 26.0；p<0.05) 和低磷血症 (OR 7.7；95%CI，1.9 至 27.0；p<0.01)。脊柱侧凸与 CM1 (OR 4.8；95%CI，1.1 至 22.8；p<0.05) 和 BI (OR=infinity；95%CI，4.7 至 infinity；p<0.01) 均相关。本研究成功地描述了 FD/MAS 中的颅底异常以及它们之间的病理生理联系。这些发现支持对颅面 FD 患者进行颅底异常的常规筛查，并对促成因素进行积极管理。 © 2018 美国骨矿研究学会。
