Genetic predisposition to developmental dysplasia of the hip

Abstract Background The aetiopathogenesis of developmental dysplasia of the hip (DDH) has not been clarified. This systematic review evaluated current literature concerning all known chromosomes, loci, genes and their polymorphisms that have been associated or not with the prevalence and severity of DDH. Methods Following the established methodology of MOOSE guidelines, MEDLINE, EMBASE, and CENTRAL were systematically searched from inception to January 2019. Findings Forty-five studies were finally included. The majority of genetic studies were Candidate Gene Association Studies assessing Chinese populations with moderate methodological quality. Among the most frequently studied, are the first, third, 12th,17th and 20th chromosomes. No gene was firmly associated with DDH phenotype. Studies from different populations often report conflicting results on the same single nucleotide polymorphism (SNP). The SNP rs143384 of GDF5 gene on chromosome 20 demonstrated the most robust relationship with DDH phenotype in association studies. The highest odds of co-inheritance in linkage studies have been reported for regions of chromosome 3 and 13. Five SNPs have been associated with the severity of DDH. Animal model studies validating previous human findings provided suggestive evidence of an inducing role of mutations of the GDF5, CX3CR1 and TENM3 genes in DDH aetiopathogenesis. Conclusion DDH is a complex disorder with environmental and genetic causes. However, no firm correlation between genotype and DDH phenotype currently exists. Systematic genome evaluation in studies with larger sample size, better methodological quality and assessment of DDH patients is necessary to clarify the DDH heredity. The role of next-generation sequencing techniques is promising.