Chiari I Malformation and Basilar Invagination in Fibrous Dysplasia: Prevalence, Mechanisms, and Clinical Implications

Abstract

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.

Neuraxial dysraphism in EPAS1- associated syndrome due to improper mesenchymal transition

“…[3][4][5] CMI is sometimes associated with syndromes that impair normal bone development, e.g., achondroplasia. 3,[6][7][8][9] We previously identified CMI and occult spinal dysraphism in 2 patients with EPAS1 gain-of-function syndrome. 10 Early somatic gain-of-function mutations in EPAS1 encoding the protein hypoxia-inducible factor-2α (HIF-2α) causes a syndrome characterized by multiple paragangliomas, somatostatinoma, and polycythemia.…”

Fibrous Dysplasia of Bone and McCune–Albright Syndrome: A Bench to Bedside Review

“…Cranial base abnormalities in FD are of concern due to the potential risk of devastating neurologic sequela. A recent study of 158 patients with craniofacial FD found that 6.3% had Chiari I malformation, while 7.6 % had secondary basilar invagination [47].…”

“…Due to the risk for cranial base abnormalities, a full neurologic exam should be performed regularly in patients with craniofacial FD, and the cranial base should be evaluated radiographically at school age and when symptomatic [47].…”

Fibrous dysplasia of occipital and temporal bone. A case report

“…[9] patient, a 14-year-old girl with polyostotic fibrous dysplasia, McCune–Albright syndrome and bilateral occipital aneurysmal bone cysts. The Pan et al [10] study clearly documents the propensity of the patients with craniofacial fibrous dysplasia toward basilar invagination and Chiari I malformation. Their detailed craniomorphometric evaluation suggests that Chiari I malformation stems from restriction of the posterior fossa volume.…”