Genetics of Degenerative Cervical Myelopathy: A Systematic Review and Meta-Analysis of Candidate Gene Studies

Abstract

Degenerative cervical myelopathy (DCM) is estimated to be the most common cause of adult spinal cord impairment. Evidence that is suggestive of a genetic basis to DCM has been increasing over the last decade. A systematic search was conducted in MEDLINE, EMBASE, Cochrane, and HuGENet databases from their origin up to 14th December 2019 to evaluate the role of single genes in DCM in its onset, clinical phenotype, and response to surgical intervention. The initial search yielded 914 articles, with 39 articles being identified as eligible after screening. We distinguish between those contributing to spinal column deterioration and those contributing to spinal cord deterioration in assessing the evidence of genetic contributions to DCM. Evidence regarding a total of 28 candidate genes was identified. Of these, 22 were found to have an effect on the radiological onset of spinal column disease, while 12 genes had an effect on clinical onset of spinal cord disease. Polymorphisms of eight genes were found to have an effect on the radiological severity of DCM, while three genes had an effect on clinical severity. Polymorphisms of six genes were found to have an effect on clinical response to surgery in spinal cord disease. There are clear genetic effects on the development of spinal pathology, the central nervous system (CNS) response to bony pathology, the severity of both bony and cord pathology, and the subsequent response to surgical intervention. Work to disentangle the mechanisms by which the genes that are reviewed here exert their effects, as well as improved quality of evidence across diverse populations is required for further investigating the genetic contribution to DCM.

The Modic‐endplate‐complex phenotype in cervical spine patients: Association with symptoms and outcomes

“…Furthermore, studies have also illustrated a genetic role in the development of cervical degeneration, ossified posterior longitudinal ligament and myelopathy. [42][43][44] In light of the evidence, the MEC may be a unique biomarker that represents a constellation of events and/or shared risk factors. As there are obvious varying etiologies of MC and endplate abnormalities and clinical impact, likewise for the MEC which needs to be further investigated.…”

Establishing Diagnostic Criteria for Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 3]

“… 7 - 10 However, optimal surgical outcomes are achieved with timely intervention, as a prolonged duration of pre-operative symptoms has been associated with poorer post-operative functional outcomes. 11 - 15 Improving early diagnosis and surgical consideration for treatment is therefore critical in improving long-term outcomes for DCM patients. 16 …”

The Role of Nutrition in Degenerative Cervical Myelopathy: A Systematic Review

“… 7 This indicates that the perception that DCM is driven uniquely by spinal cord compression is an over-simplification, 8 and additional, dynamic factors must contribute to the aetiology of DCM, and/or influence the vulnerability of the spinal cord. Early investigations have identified candidate genetic determinants in small series, 9 but environmental factors are also likely.…”