Last Week's Medical Mystery

Each of these patients presented with physical findings of a "tracheal tug" and a high-pitched diastolic murmur loudest over the right second intercostal space that radiated down the right sternal border. In addition, each patient has his/her unique physical findings (see images below) but all carry a unifying diagnosis.

What is your diagnosis, what test(s) would you order to confirm your suspicions, and what treatment, if any, do you recommend?

DIAGNOSIS: Loeys-Dietz syndrome, an autosomal dominant syndrome characterized by the degeneration of collagen and elastic fibers in the tunica media of the proximal aorta (medial sclerosis) and the subsequent development of aortic aneurysms and arterial tortuosity.

The disorder may be associated with hyperteleorism (patient A), marked thinning of the skin (patient B) and bifid uvula (patient C). Other phenotypic abnormalities may include micrognathia, cleft palate, and proptosis. The entity is due to mutations in the genes encoding transforming growth factor beta receptors 1 and 2. In contrast to patients with Ehlers-Danlos syndrome type IV, these patients have a low rate of intraoperative mortality during vascular repair surgery. Patients with Loeys-Dietz syndrome, Marfan syndrome, and Ehlers-Danlos syndrome type IV are at risk of dying from an aortic dissection.

The described findings in the presented case are characteristic of an aneurysm of the ascending aorta (tracheal tug) and consequent dilation of the sinuses of Valsalva (the murmur of aortic regurgitation).