Diagnosis and Management of Loeys-Dietz Syndrome: Evidence Gaps and Future Directions

This review summarizes current knowledge on Loeys-Dietz syndrome (LDS), including its genetic basis, multisystem manifestations, diagnosis, surveillance, and management. It also highlights key evidence gaps in risk stratification, medical therapy, imaging surveillance, surgical thresholds, and care of pregnant and pediatric patients.

Although understanding of the genetic basis and clinical spectrum of LDS has improved, LDS-specific evidence remains limited. LDS is increasingly recognized as a multisystem disorder with aggressive aortic disease, extra-aortic vascular involvement, skeletal, craniofacial, allergic, gastrointestinal, and neurodevelopmental manifestations. Current recommendations are largely based on expert consensus and experience with related connective tissue disorders. Most available research focuses on the aortic root and ascending aorta, with less evidence guiding management of peripheral vascular disease. LDS requires early diagnosis, individualized risk assessment, and multidisciplinary longitudinal care supported by genetic evaluation, biomarker-based approaches, multimodality imaging, and structured surveillance. Future research should focus on multicenter registries, genotype-phenotype correlations, biomarker validation, advanced imaging, and LDS-specific therapeutic studies to develop evidence-based guidelines and improve long-term outcomes.