Arterial tortuosity syndrome: phenotypic and cardiovascular features in 4 newly identified patients

Abstract

Abstract Arterial tortuosity syndrome (ATS) is an autosomal recessive connective tissue disease caused by biallelic variants in the SLC2A10gene and characterized by tortuosity and elongation of the aorta and medium-sized arteries. It’s considered an extremely rare disease; only 106 individuals with genetically confirmed ATS have been identified to date. The aim of this study is to contribute to the phenotypic, cardiovascular and genetic characterization of this disease. Four cases of ATS from two families are described, contributing to the clinical delineation of the entity. Two cases with diaphragmatic hernia and a case with complex uropathy, reported in the literature only 11 times, are highlighted. Regarding the vascular involvement, a predominant supra-aortic affectation stands out and only 1 case of focal stenosis is detected (renal artery). All presented severe intracranial tortuosity. To reduce hemodynamic stress on the arterial wall, beta-adrenergic blocking treatment was prescribed. A not previously described mutation (c.899T>G (p.Leu300Trp)) is presented in a proband; it has an allegedly deleterious effect in compound heterozygosis with the pathogenic variant c.417T>A (p.Tyr139Ter). The 3 other patients, siblings born from healthy consanguineous parents, had an homozygous variant in SLC2A10: c.510G>A (p.Trp170Ter).