Adult presentation of arterial tortuosity syndrome in a 51‐year‐old woman with a novel homozygous c.1411+1G>A mutation in the SLC2A10 gene

Arterial tortuosity syndrome (ATS) is an autosomal recessive connective tissue disorder, mainly characterized by tortuosity and elongation of the large‐ and medium‐sized arteries with predisposition to stenoses and aneurysms. ATS is caused by mutations in the SLC2A10 gene, encoding for the facilitative glucose transporter 10 (GLUT10) and is described typically in pediatric patients. We report on a 51‐year‐old woman, originally ascertained because of unexplained widespread chronic pain and positive family history of aortic malformation. The main findings included aged appearance, congenital joint hypermobility, joint instability complications, chronic fatigue syndrome, progressive painful joint stiffness, abdominal hernias, pelvic prolapses, multiple cardiac valve prolapses, varicose veins, easy bruising, and gingival recession. Vascular imaging revealed kinking and anomalous origin of the aortic arch branches, marked tortuosity of the aorta, pulmonary and most middle arteries, and a small aneurysm of the splenic artery. SLC2A10 analysis disclosed homozygosity for the novel c.1411+1G>A splice mutation, leading to a 41 amino acids GLUT10 internal deletion. Expression study by immunofluorescence using healthy control cells showed lack of membrane internalization of GLUT10 in patient's skin fibroblasts. This report describes the first splice‐site SLC2A10 mutation and increases to 19 the repertoire of known mutations in this gene. Comparison with the few previously published adult patients with ATS contributes to the natural history of this condition, which is probably under diagnosed within the expanding family of inherited connective tissue disorders. © 2012 Wiley Periodicals, Inc.