Clinical features and complications of Loeys-Dietz syndrome: A systematic review

Introduction: Loeys-Dietz syndrome (LDS) is a connective tissue disorder that arises from mutations altering the transforming growth factor 1 signalling pathway. Due to the recent discovery of the underlying genetic mutations leading to LDS, the spectrum of characteristics and complications is not fully understood. Methods: Our search included five databases (Pubmed, SCOPUS, Web of Science, EMBASE and google scholar) and included variations of Loeys-Dietz Syndrome as search terms, using all available data until February 2021. All study types were included. Three reviewers screened 1394 abstracts, of which 418 underwent full-text review and 392 were included in the final analysis. Results: We identified 3896 reported cases of LDS with the most commonly reported features and complications being: aortic aneurysms and dissections, arterial tortuosity, high arched palate, abnormal uvula and hypertelorism. LDS Types 1 and 2 share many clinical features, LDS Type 2 appears to have a more aggressive aortic disease. LDS Type 3 demonstrated an increased prevalence of mitral valve prolapse and arthritis. LDS Type 4 and 5 demonstrated a lower prevalence of musculoskeletal and cardiovascular involvement. Amongst 222 women who underwent 522 pregnancies, 4% experienced an aortic dissection and the peripartum mortality rate was 1%. Conclusion: We observed that LDS is a multisystem connective tissue disorder that is associated with a high burden of complications, requiring a multidisciplinary approach. Ongoing attempts to better characterise these features will allow clinicians to appropriately screen and manage these complications.

Automated summary

Loeys-Dietz syndrome (LDS) is a multisystem connective tissue disorder caused by mutations in the transforming growth factor 1 signalling pathway. It is characterized by features such as aortic aneurysms and dissections, arterial tortuosity, and high arched palate. Different types of LDS have varying clinical features and complications, with LDS Type 2 being associated with more severe aortic disease.