The Loeys-Dietz syndrome: an update for the clinician

Thoracic aortic aneurysm (TAA) dissection is an important cause of death in the western world. Especially in young adults, the genetic contribution to this disease is estimated to be high, as at least one out of five probands has a positive family history for aortic aneurysms/dissections. In recent years, major progress has been made in the identification of several genes underlying both syndromic and nonsyndromic forms of TAA.

This review will focus on the current knowledge of a recently discovered syndromic form of TAA, namely the Loeys-Dietz syndrome or LDS.

LDS is caused by mutation in the genes encoding the transforming growth factor beta receptor 1 and 2 (TGFBR1 and TGFRB2) and is characterized by aggressive aortic/arterial disease. The clinical characteristics, molecular findings and pathophysiological mechanisms are summarized. The discovery of this entity has confirmed a key role for transforming growth factor beta signaling in aortic aneurysmal disease. Study of the natural history of this condition has revealed important lessons. The arterial disease is widespread and can involve all aortic segments and major branching arteries, necessitating cardiovascular imaging beyond the aortic root segment. Moreover, dissections occur at smaller diameters than in Marfan syndrome, leading to earlier surgery at smaller aortic diameters. Current surgical experience with LDS is excellent, offering a good long-term prognosis with timely identification of the disease.