Aortic root dilatation and mitral valve prolapse in three siblings with dental anomalies and short stature syndrome due to a homozygous novel LTBP3 variant.

Abstract

The latent transforming growth factor-beta-binding protein 3 (LTBP3), which encodes one of the extracellular matrix proteins, plays an essential role in skeletal formation through both stimulatory and inhibitory effects on the growth of different cell types, as well as on the production and degradation of the extracellular matrix. Pathogenic variants in LTBP3 have been associated with genetic skeletal disorders that exhibit various cardiovascular features, including aortic root dilatation, aneurysm or dissection of the ascending and descending aorta, and mitral valve prolapse). Aortic root dilatation, an aortopathy that may have lifethreatening consequences, is among the clinical findings in various connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Aortic root dilatation, aneurysm, and aortic dissection should be carefully investigated by cardiologists. In this study, we describe three siblings with short stature and dental anomalies. A homozygous, novel, c.2726-1G > A pathogenic variant in LTBP3 was identified through exome sequencing. After the detection of the LTBP3 variant, the patients were evaluated for possible cardiac findings, which revealed mitral valve prolapse and aortic root dilatation despite the absence of clinical symptoms. In this study, we aimed to shed light on the diagnosis of dental anomalies and short tature syndrome in three siblings with a novel LTBP3 pathogenic variant revealed through exome sequencing. Additionally, we emphasise the importance of searching for cardiac findings, even in the absence of clinical symptoms. We highly suggest that cardiologists take note of cardiac findings in patients with dental anomalies and short stature syndrome.