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

Abstract Background and purpose: Arterial tortuosity syndrome (ATS) is an autosomal recessive connective tissue disease caused by biallelic variants in the SLC2A10 gene and characterized by tortuosity and elongation of the aorta and medium-sized arteries, focal stenosis and aneurysm formation. 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 and cardiovascular description of this disease, as well as its genetic characterization. Methods and results: Four cases of ATS from two families are described: 3 siblings born from healthy consanguineous parents with an homozygous variant in SLC2A10: c.510G>A (p.Trp170Ter) and a child with two heterozygous variants: c.417T>A (p.Tyr139Ter), classified as pathogenic, and c.899T>G (p.Leu300Trp), not previously described as pathogenic but with an allegedly deleterious effect in compound heterozygosis. The presented clinical spectrum is wide; two cases with diaphragmatic hernia and a complex uropathy are highlighted. Regarding the vascular involvement, a predominant supra-aortic affectation stands out with less involvement in abdominal aorta, visceral branches and lower extremities. No aneurysms were observed and only 1 case of focal stenosis (renal artery). All presented severe intracranial tortuosity. No case of intracardiac involvement is described. To reduce hemodynamic stress on the arterial wall, beta-adrenergic blocking treatment was prescribed. Conclusions: four novel pediatric cases are described, contributing to the clinical delineation of the entity. A case with complex uropathy, reported in the literature only 11 times, is included. Moreover, a not previously described mutation is presented; with an allegedly deleterious effect in association with another pathogenic variable.