Whole-Exome Sequencing Analysis Identifies Risk Genes in Atlantoaxial Dislocation Patients with Sandwich Fusion

Sandwich fusion of Klippel-Feil syndrome (KFS), which is a rare congenital disorder involving the fusion of cervical vertebrae, poses significant challenges in the diagnosis and treatment of atlantoaxial dislocation (AAD). While the disorder’s genetic basis is not well-understood, the rarity of the sandwich fusion makes it difficult to study. Whole-exome sequencing (WES) was conducted on 68 unrelated Chinese patients with sandwich fusion. The study compared their genetic data with a control group of 219 individuals without musculoskeletal disorders. Various analyses, including mutational burden assessments, were employed to identify potential pathogenic genes. The study identified significant genetic variations in patients with sandwich fusion, highlighting genes like KMT5A, HYDIN, and PCDHB4 as potential contributors. Notably, severe cases exhibited oligogenic effects, with mutations in genes like MEOX1 associated with the severity of spinal issues. These findings offer critical insights into the genetic basis of sandwich fusion and provide a foundation for future research and therapeutic development.