Advances in Clinical Genetics of the Ehlers-Danlos Syndromes

Abstract

The Ehlers-Danlos syndromes (EDS) are a group of rare hereditary connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. The clinical and genetic hetero- geneity of EDS frequently leads to underdiagnosis and misdiagnosis. Genetic testing is an essential approach to clarify the underlying diagnosis. Recent research has preliminarily established genotype-phenotype correlations and introduced the novel concept of " disease spectrum" in some subtypes. These studies deepen our understanding of EDS etiology and provide important insights into clinical management. Published in 2023, the Chinese Guidelines for Diagnosis and Treatment of the Ehlers-Danlos Syndromes(the Guidelines) recommend performing genetic testing with deep phenotyping for patients who meet the clinical diagnostic criteria or are suspected of having EDS. However, it should be noted that the clinical diagnosis might differ from the molecular diagnosis. Furthermore, cutting-edge approaches such as periodic data reanalysis, integration of RNA sequencing into family-based whole-genome sequencing, and third-generation sequencing may facilitate the reclassification of variants of uncertain significance or resolve undiagnosed cases. This article summarizes recent progress in the genetics research of EDS, with the hope of offering a valuable resource for clinical diagnosis, treatment and scientific research to optimize the quality of life of patients with EDS.

Keywords

• ehlers-danlos syndromes
• clinical genetics
• genotype-phenotype correlation
• whole genome sequencing
• rna sequencing
• deep phenotyping