Arterial tortuosity syndrome: 40 new families and literature review

Aude Beyens, Juliette Albuisson, Annekatrien Boel, Mazen Al-Essa, Waheed Al-Manea, Damien Bonnet, Ozlem Bostan, Odile Boute, Tiffany Busa, Nathalie Canham, Ergun Cil, Paul J. Coucke, Margot A. Cousin, Majed Dasouki, Julie De Backer, Anne De Paepe, Sofie De Schepper, Deepthi De Silva, Koenraad Devriendt, Inge De WandeleDavid R. Deyle, Harry Dietz, Sophie Dupuis-Girod, Eudice Fontenot, Björn Fischer-Zirnsak, Alper Gezdirici, Jamal Ghoumid, Fabienne Giuliano, Neus Baena Diéz, Mohammed Z. Haider, Joshua S. Hardin, Xavier Jeunemaitre, Eric W. Klee, Uwe Kornak, Manuel F. Landecho, Anne Legrand, Bart Loeys, Stanislas Lyonnet, Helen Michael, Pamela Moceri, Shehla Mohammed, Laura Muiño-Mosquera, Sheela Nampoothiri, Karin Pichler, Katrina Prescott, Anna Rajeb, Maria Ramos-Arroyo, Massimiliano Rossi, Mustafa Salih, Mohammed Z. Seidahmed, Elise Schaefer, Elisabeth Steichen-Gersdorf, Sehime Temel, Fahrettin Uysal, Marine Vanhomwegen, Lut Van Laer, Lionel Van Maldergem, David Warner, Andy Willaert, Tom R. Collins, Andrea Taylor, Elaine C. Davis, Yuri Zarate, Bert Callewaert

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1236-1245
Number of pages10
JournalGenetics in Medicine
Volume20
Issue number10
DOIs
StatePublished - Oct 1 2018

ASJC Scopus subject areas

  • Genetics(clinical)

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    Beyens, A., Albuisson, J., Boel, A., Al-Essa, M., Al-Manea, W., Bonnet, D., Bostan, O., Boute, O., Busa, T., Canham, N., Cil, E., Coucke, P. J., Cousin, M. A., Dasouki, M., De Backer, J., De Paepe, A., De Schepper, S., De Silva, D., Devriendt, K., ... Callewaert, B. (2018). Arterial tortuosity syndrome: 40 new families and literature review. Genetics in Medicine, 20(10), 1236-1245. https://doi.org/10.1038/gim.2017.253