[Molecular genetic background of developmental bony malformations at the craniocervical junction and cervical spine]. / A nyaki gerinc és a craniocervicalis átmenet csontos-fúziós fejlódési rendellenességeinek molekuláris genetikai háttere.

In this review a new interpretation of the origin of bony developmental malformations affecting the craniocervical junction and the cervical spine is presented based on recent advances in the understanding of embryonic development of the spine and its molecular genetic control. Radiographs, CT and MRI scans or CT myelograms of patients with Klippel-Feil syndrome were used for demonstration. Detailed clinical and radiological analysis of these patients was published earlier [David KM, Stevens JM, Thorogood P, Crockard HA. The dysmorphic cervical spine in Klippel-Feil syndrome: interpretations from developmental biology. Neurosurg Focus 1999;6(6):1.]. Homeotic transformation due to mutations or disturbed expression of Hox genes is a possible mechanism responsible for Cl assimilation. Notochordal defects and/or signalling problems, that result in reduced or impaired Pax-1 gene expression, may underlie vertebral fusions. This, together with asymmetrical distribution of paraxial mesoderm cells and a possible lack of communication across the embryonic mid-line, could cause the asymmetrical fusion patterns. The wide and flattened shape of the fused vertebral bodies, their resemblance to the embryonic cartilaginous vertebrae and the process of progressive bony fusion with age suggest that the fusions occur before or, at the latest, during chondrification of vertebrae. The authors suggest that the aforementioned mechanisms are likely to be, at least in part, responsible for the origin of the bony developmental malformations affecting the craniocervical junction and the cervical spine.

The dysmorphic cervical spine in Klippel-Feil syndrome: interpretations from developmental biology.

The authors conducted a study to identify radiological patterns of Klippel-Feil syndrome (KFS), and they present a new interpretation of the origin of these patterns based on recent advances in understanding of embryonic development of the spine and its molecular genetic control. The authors studied radiographs and computerized tomography (CT) scans as well as magnetic resonance images or CT myelograms obtained in 30 patients with KFS who were referred for treatment between 1982 and 1996; the patients had complained of various neuroorthopedic complications. Homeotic transformation due to mutations or disturbed expression of Hox genes is a possible mechanism responsible for C-1 assimilation, which was found to have occurred in 19 cases (63%). Notochordal defects and/or signaling problems, which result in reduced or impaired Pax-1 gene expression, may underlie vertebral fusions. This, together with asymmetrical distribution of paraxial mesoderm cells and a possible lack of communication across the embryonic midline, could cause asymmetrical fusion patterns, which were present in 17 cases (57%). The wide and flattened shape of the fused vertebral bodies and their resemblance to the embryonic cartilaginous vertebrae as well as the process of progressive bone fusion with age suggest that the fusions occur before or, at the latest, during chondrification of vertebrae. The authors suggest that the aforementioned mechanisms are likely to be, at least in part, responsible for the observed patterns in KFS that affect the craniovertebral junction and the cervical spine.