Dataset Information

Weak Ligaments and Sloping Joints: A New Hypothesis for Development of Congenital Atlantoaxial Dislocation and Basilar Invagination.

ABSTRACT:

Objective

Developmental bony craniovertebral junction (CVJ) anomalies seem to have a genetic basis and also abnormal joint morphology causing atlantoaxial dislocation (AAD) and basilar invagination (BI).

Methods

DNA extracted polymerase chain reaction single-stranded conformation polymorphism (SSCP) performed for mutation screening of FBN1 gene (n = 50 cases+ 50 age/sex-matched normal; total: 100). Samples with a deviated pattern of bands in SSCP were sequenced to detect the type of variation. Computed tomography (CT) scans of 100 patients (15-45 years old) compared with an equal number of age/sex-matched controls (21.9 ± 8.2 years). Joint parameters studied: sagittal joint inclination (SI), craniocervical tilt (CCT), coronal joint inclination (CI).

Results

Thirty-nine samples (78%) showed sequence variants. Exon 25, 26, 27, and 28 showed variable patterns of DNA bands in SSCP, which on sequencing gives various types of DNA sequence variations in intronic region of the FBN1 gene in 14%, 14%, 6%, and 44% respectively. CT radiology:SI and CCT correlated with both BI and AAD (p < 0.01). The mean SI value in controls: 83.35° ± 8.65°, and in patients with BI and AAD:129° ± 24.05°. Mean CCT in controls: 60.2° ± 9.2°, and in patients with BI and AAD: 86.0° ± 18.1°. Mean CI in controls:110.3° ± 4.23°, and in cases: 125.15° ± 16.4°.

Conclusion

The study showed mutations in FBN1 gene (reported in Marfan syndrome). There is also an alteration of joint morphology, correlating with AAD and BI severity. Hence, we propose a double-hit hypothesis: the presence of weak ligaments (due to FB1 gene alterations) and abnormal joint morphology may contribute to AAD and BI.

SUBMITTER: Chauhan AK

PROVIDER: S-EPMC7788422 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Weak Ligaments and Sloping Joints: A New Hypothesis for Development of Congenital Atlantoaxial Dislocation and Basilar Invagination.

Chauhan Avnish K AK Chandra P Sarat PS Goyal Nishant N Chowdhury Madhumita R MR Banerjee Jyotirmoy J Tripathi Manjari M Kabra Madhulika M

Neurospine 20201231 4

<h4>Objective</h4>Developmental bony craniovertebral junction (CVJ) anomalies seem to have a genetic basis and also abnormal joint morphology causing atlantoaxial dislocation (AAD) and basilar invagination (BI).<h4>Methods</h4>DNA extracted polymerase chain reaction single-stranded conformation polymorphism (SSCP) performed for mutation screening of FBN1 gene (n = 50 cases+ 50 age/sex-matched normal; total: 100). Samples with a deviated pattern of bands in SSCP were sequenced to detect the type ...[more]

PMID: 33401861

Similar Datasets

Project description: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.

Dataset Information

Weak Ligaments and Sloping Joints: A New Hypothesis for Development of Congenital Atlantoaxial Dislocation and Basilar Invagination.

Objective

Methods

Results

Conclusion

Publications

Weak Ligaments and Sloping Joints: A New Hypothesis for Development of Congenital Atlantoaxial Dislocation and Basilar Invagination.

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