Clinical Exome Sequencing as a Novel Tool for Diagnosing Loeys-Dietz Syndrome Type 3

Abstract

Objective/background: In rare genetic vascular syndromes the diagnosis may not be apparent from the phenotype, but might be important for proper management.

Methods: A previously healthy woman without dysmorphic features presented with pregnancy associated vascular dissections and aneurysms. Next generation clinical exome sequencing was performed.

Results: The differential diagnosis of spontaneous arterial dissection is outlined. The patient's diagnosis became evident after clinical exome sequencing detected a novel missense mutation in the evolutionary conserved region of SMAD3, confirming the diagnosis of Loeys-Dietz syndrome (LDS) type 3. A brief overview of the various types of LDS and their management is presented.

Conclusion: Clinical exome sequencing proved useful in diagnosing LDS type 3 where detailed vascular surveillance and timely intervention with a low threshold is recommended.

Keywords: Aneurysm; Clinical exome sequencing; Loeys-Dietz syndrome; Pregnancy; Spontaneous arterial dissection.