The genetics of ossification of the posterior longitudinal ligament

Object Ossification of the posterior longitudinal ligament (OPLL) is a pathological process of ectopic calcification with a preponderance for the cervical spine. Epidemiological and familial studies have both indicated predisposition; however, the genetic inheritance pattern and responsible genes for OPLL are still uncertain. The aim of this study was to evaluate and summarize the current understanding of the genetics underlying OPLL. Methods The authors reviewed epidemiological and genetic studies surrounding OPLL, with a particular focus on inheritance patterns and potential genes responsible for OPLL, using a PubMed database literature search. Results Despite an unclear inheritance pattern, there appears to be a strong familial link in patients with OPLL. Examination of these patterns using linkage analysis has shown multiple candidate genes that could be responsible for the inheritance of OPLL. Genes for collagen, nucleotide pyrophosphatase, transforming growth factors, and the vitamin D receptor have all been implicated. Additionally, multiple cytokines and growth factors, including bone morphogenetic proteins as well as other proteins and interleukins involved in bone development, have been shown to be abnormally expressed in patients with OPLL. In addition, multiple mechanical and metabolic factors such as hyperinsulinemia and obesity have been shown to be linked to OPLL. Conclusions Ossification of the posterior longitudinal ligament has a complex inheritance pattern. It does not appear that OPLL follows a simple, single-gene Mendelian inheritance pattern. Development of OPLL is more likely multifactorial in nature and develops in patients with a genetic predisposition from a variety of different mutations in various genes on various chromosomes. Additionally, environmental factors and interaction by other pathological disease processes, such as obesity and diabetes mellitus, may play a role in the development of OPLL in susceptible individuals.