Loeys-Dietz syndrome

LDS is a heritable disorder of the connective tissue characterized by multisystem involvement, including craniofacial features, skeletal abnormalities, cutaneous findings, and early-onset and aggressive disease of the aorta and its branches.

LDS is linked to mutations in genes encoding components of the transforming growth factor-beta signaling pathway. These mutations lead to an overactivation of the transforming growth factor-beta signaling pathway, which plays a crucial role in the growth and development of connective tissues throughout the body. This overactivation results in the abnormal development of various tissues, particularly those in the heart, blood vessels, and skeletal system.

The estimated worldwide prevalence of LDS is estimated at 0.00074 per 100,000 population.

Risk factors for LDS include specific pathogenic variants in TGFBR1, TGFBR2, SMAD3, TGFB2, and TGFB3 genes. These genetic variants may contribute to a more severe disease phenotype. Additionally, a familial history of the syndrome is associated with an increased risk.

Clinical manifestations include craniofacial features, skeletal abnormalities such as long and slender limbs (arachnodactyly), joint laxity, and chest deformities (pectus excavatum), cutaneous findings, and early-onset and aggressive disease of the aorta and its branches. Vascular complications, such as arterial tortuosity and aneurysms, are common and distinctive features of LDS. These vascular abnormalities can lead to serious events like aortic aneurysm rupture, which can be life-threatening.

The prognosis is variable and is largely dependent on the patient's specific genetic mutations and the management of associated cardiovascular complications.