Arterial tortuosity syndrome: 40 new families and literature review

Aude Beyens 1, Juliette Albuisson 2, Annekatrien Boel 1, Mazen Al-Essa 3, Waheed Al-Manea 4, Damien Bonnet 5, Ozlem Bostan 6, Odile Boute 7, Tiffany Busa 8, Nathalie Canham 9, Ergun Cil 6, Paul J Coucke 1, Margot A Cousin 10 11, Majed Dasouki 12, Julie De Backer 1 13, Anne De Paepe 1, Sofie De Schepper 14, Deepthi De Silva 15 16, Koenraad Devriendt 17, Inge De Wandele 1, David R Deyle 10 18 19, Harry Dietz 20, Sophie Dupuis-Girod 21, Eudice Fontenot 22, Björn Fischer-Zirnsak 23, Alper Gezdirici 24, Jamal Ghoumid 25, Fabienne Giuliano 26, Neus Baena Diéz 27, Mohammed Z Haider 3, Joshua S Hardin 28, Xavier Jeunemaitre 2, Eric W Klee 10 11 18, Uwe Kornak 23, Manuel F Landecho 29, Anne Legrand 2, Bart Loeys 30, Stanislas Lyonnet 5, Helen Michael 31, Pamela Moceri 32, Shehla Mohammed 33, Laura Muiño-Mosquera 1, Sheela Nampoothiri 34, Karin Pichler 35, Katrina Prescott 36, Anna Rajeb 23, Maria Ramos-Arroyo 37, Massimiliano Rossi 38, Mustafa Salih 39, Mohammed Z Seidahmed 4, Elise Schaefer 40, Elisabeth Steichen-Gersdorf 35, Sehime Temel 41 42 43, Fahrettin Uysal 6, Marine Vanhomwegen 1, Lut Van Laer 30, Lionel Van Maldergem 44, David Warner 28, Andy Willaert 1, Tom R Collins 22, Andrea Taylor 45, Elaine C Davis 46, Yuri Zarate 10, Bert Callewaert 47

Affiliations

01 October 2018

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doi: 10.1038/gim.2017.253

Abstract

Purpose: We delineate the clinical spectrum and describe the histology in arterial tortuosity syndrome (ATS), a rare connective tissue disorder characterized by tortuosity of the large and medium-sized arteries, caused by mutations in SLC2A10.

Methods: We retrospectively characterized 40 novel ATS families (50 patients) and reviewed the 52 previously reported patients. We performed histology and electron microscopy (EM) on skin and vascular biopsies and evaluated TGF-β signaling with immunohistochemistry for pSMAD2 and CTGF.

Results: Stenoses, tortuosity, and aneurysm formation are widespread occurrences. Severe but rare vascular complications include early and aggressive aortic root aneurysms, neonatal intracranial bleeding, ischemic stroke, and gastric perforation. Thus far, no reports unequivocally document vascular dissections or ruptures. Of note, diaphragmatic hernia and infant respiratory distress syndrome (IRDS) are frequently observed. Skin and vascular biopsies show fragmented elastic fibers (EF) and increased collagen deposition. EM of skin EF shows a fragmented elastin core and a peripheral mantle of microfibrils of random directionality. Skin and end-stage diseased vascular tissue do not indicate increased TGF-β signaling.

Conclusion: Our findings warrant attention for IRDS and diaphragmatic hernia, close monitoring of the aortic root early in life, and extensive vascular imaging afterwards. EM on skin biopsies shows disease-specific abnormalities.

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