Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and chiari malformation type I in patients with hereditary disorders of connective tissue

J Neurosurg Spine. 2007 Dec;7(6):601-9. doi: 10.3171/SPI-07/12/601.


Object: Chiari malformation Type I (CM-I) is generally regarded as a disorder of the paraxial mesoderm. The authors report an association between CM-I and hereditary disorders of connective tissue (HDCT) that can present with lower brainstem symptoms attributable to occipitoatlantoaxial hypermobility and cranial settling.

Methods: The prevalence of HDCT was determined in a prospectively accrued cohort of 2813 patients with CM-I. All patients underwent a detailed medical and neuroradiological workup that included an assessment of articular mobility. Osseous structures composing the craniocervical junction were investigated morphometrically using reconstructed 3D computed tomography and plain x-ray images in 114 patients with HDCT/CM-I, and the results were compared with those obtained in patients with CM-I (55 cases) and healthy control individuals (55 cases).

Results: The diagnostic criteria for Ehlers-Danlos syndrome and related HDCT were met in 357 (12.7%) of the 2813 cases. Hereditability was generally compatible with a pattern of autosomal dominant transmission with variable expressivity. The diagnostic features of HDCT/CM-I were distinguished from those of CM-I by clinical stigmata of connective tissue disease, a greater female preponderance (8:1 compared with 3:1, p < 0.001), and a greater incidence of lower brainstem symptoms (0.41 compared with 0.11, p < 0.001), retroodontoid pannus formation (0.71 compared with 0.11, p < 0.001), and hypoplasia of the oropharynx (0.44 compared with 0.02, p < 0.001). Measurements of the basion-dens interval, basion-atlas interval, atlas-dens interval, dens-atlas interval, clivus-atlas angle, clivus-axis angle, and atlas-axis angle were the same in the supine and upright positions in healthy control individuals and patients with CM-I. In patients with HDCT/CM-I, there was a reduction of the basion-dens interval (3.6 mm, p < 0.001), an enlargement of the basion-atlas interval (3.0 mm, p < 0.001), and a reduction of the clivus-axis angle (10.8 degrees, p < 0.001), clivus-atlas angle (5.8 degrees, p < 0.001), and atlas-axis angle (5.3 degrees, p < 0.001) on assumption of the upright position. These changes were reducible by cervical traction or returning to the supine position.

Conclusions: The identification of HDCT in 357 patients with CM-I establishes an association between two presumably unrelated mesodermal disorders. Morphometric evidence in this cohort-cranial settling, posterior gliding of the occipital condyles, and reduction of the clivus-axis angle, clivus-atlas angle, and atlas-axis angle in the upright position-suggests that hypermobility of the occipitoatlantal and atlantoaxial joints contributes to retroodontoid pannus formation and symptoms referable to basilar impression.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arnold-Chiari Malformation / complications*
  • Arnold-Chiari Malformation / diagnostic imaging
  • Arnold-Chiari Malformation / therapy
  • Atlanto-Axial Joint* / diagnostic imaging
  • Atlanto-Occipital Joint* / diagnostic imaging
  • Child
  • Child, Preschool
  • Cohort Studies
  • Connective Tissue Diseases / complications*
  • Connective Tissue Diseases / genetics*
  • Connective Tissue Diseases / therapy
  • Ehlers-Danlos Syndrome / complications
  • Ehlers-Danlos Syndrome / genetics
  • Female
  • Genes, Dominant
  • Humans
  • Image Processing, Computer-Assisted
  • Imaging, Three-Dimensional
  • Joint Instability / diagnostic imaging
  • Joint Instability / etiology*
  • Male
  • Middle Aged
  • Prospective Studies
  • Skull / diagnostic imaging*
  • Syndrome
  • Tomography, X-Ray Computed
  • Traction