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

Abstract

<jats:p>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.</jats:p> <jats:p>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.</jats:p> <jats:p>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.</jats:p>

Superior odontoid migration in the Klippel–Feil patient

“…KFS is a well-known developmental disorder whose positioning of the odontoid could stem from several factors. For example, it has been postulated that the fusion process in KFS patients is not fully present at birth and could be ongoing until skeletal maturity [10,54]. In that sense, migration or translocation of the odontoid could develop from physical strain applied upon the craniovertebral junction due to a lack of motion in the cervical region where fused segments are pronounced and where cervical alignment is compensated; thus, more or less a function of time could be involved coupled with the deformity byproducts of the condition that contribute to the spatial orientation of the odontoid.…”

“…Excessive SOM could increase the threat of neurologic compromise and potentially death [11,12,30,39,50]. SOM has been associated with various disorders, such as rheumatoid arthritis [13,17,35,42,48], Down's syndrome [34,52], osteogenesis imperfecta [30,47], and Klippel-Feil syndrome (KFS) [1,10,18].…”

“…This developmental condition is uncommon and believed to occur in 1 in 40,000-42,000 births [22,26]. Various spinal and extraspinal anomalies have been associated with KFS, but vary between individuals [10,23,25,36,37,44,46,53]. Moreover, up to 68% of KFS patients, primarily noted in adulthood, report symptoms related to their syndrome [2,20,43,44,46].…”

Cervical instability in Klippel-Feil syndrome: case report and review of the literature

“…The incidence of KFS has been estimated to be anywhere from 1 in 40,000 to 50,000 live births [4,20], with some studies suggesting a slight female predominance [13,18,21,22]. While a number of genes have been described in association with KFS, the exact etiology remains unknown [20,23].…”

A 6-Year Experience of 100 Cases of Pediatric Bony Craniovertebral Junction Abnormalities: Treatment and Outcomes

“…The immaturity of bones and the implications of the posterior fusion on bone growth are major concerns while deciding the management strategies in this age group. Moreover, the radiological picture is confusing as the ossification of the bones is completed only by 9 years of age [4]. The incidence of different types of abnormalities varies with the demographic environment [5,6] and has ill-defined genetic factors [7,8].…”