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Genet Med. 2018 Oct;20(10):1236-1245. doi: 10.1038/gim.2017.253. Epub 2018 Jan 11.

Arterial tortuosity syndrome: 40 new families and literature review.

Author information

1
Center For Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium.
2
APH, Hôpital Européen Georges Pompidou, Centre de Référence des Maladies Vasculaires Rares, INSERM, U970, Université Descartes Paris, Sarbonne Cité, Paris, France.
3
Pediatrics Department, Kuwait University, Kuwait City, Kuwait.
4
Pediatric Department, Security Forces Hospital, Riyadh, Kingdom of Saudi Arabia.
5
Medical Genetics Service, Hôpital Necker-Enfants Malades, Paris, France.
6
Department of Pediatric Cardiology, University of Uludag, Bursa, Turkey.
7
Clinical Genetics Service "Guy Fontaine," Hôpital Calmette, Lille, France.
8
Service de Génétique Clinique, Département de Génétique, AP-HM CHU Timone Enfants, Marseille, France.
9
North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow, United Kingdom.
10
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
11
Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
12
Department of Pediatrics, University of Kansas, Kansas City, Kansas, USA.
13
Department of Cardiology, Ghent University Hospital, Ghent, Belgium.
14
Department of Dermatology, Ghent University Hospital, Ghent, Belgium.
15
Department of Physiology, University of Kelaniya, Ragama, Sri Lanka.
16
Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
17
Center for Human Genetics, Leuven University Hospital, Leuven, Belgium.
18
Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA.
19
Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
20
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
21
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfants, Service de Génétique et Centre de Référence Pour la Maladie de Rendu-Osler, Université Lyon, Lyon, France.
22
Division of Cardiology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
23
Institute of Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
24
Department of Medical Genetics, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey.
25
Department of Medical Genetics, Lille University Hospital, CHU Lille, Lille, France.
26
Department of Physical Medicine and Rehabilitation, Raymond Poincare Hospital, Garches, France.
27
Genetics Laboratory UDIAT Diagnostic Center, Parc Tauli University Hospital, Sabadell, Spain.
28
Department of Ophthalmology, Arkansas Children's Hospital, Little Rock, Arkansas, USA.
29
Department of Internal Medicine, Clínica Universidad de Navarra, Pamplona, Spain.
30
Center of Medical Genetics, University Hospital of Antwerp, Antwerp, Belgium.
31
Paediatric Cardiology and Transition, Leeds General Infirmary, Leeds, United Kingdom.
32
Cardiology Department, Université Côte d'Azur, CHU de Nice et Hôpitaux Universitaires Pédiatriques Lenval, Nice, France.
33
South East Thames Regional Genetics Service, Guy's Hospital, London, United Kingdom.
34
Department of Pediatric Genetics, Amrita Institute of Medical Sciences and Research Center, Cochin, Kerala, India.
35
Clinic for Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria.
36
Clinical Genetics, Yorkshire Regional Genetics Service, Leeds, United Kingdom.
37
Medical Genetics Service, Complejo Hospitalario de Navarra, Pamplona, Spain.
38
Genetic Department, Femme-Mère-Enfant Hospital, Hospices Civils de Lyon and INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, GENDEV Team, Université Claude Bernard Lyon 1, Bron, France.
39
Division of Pediatric Neurology, King Saud University, Riyadh, Kingdom of Saudi Arabia.
40
Medical Genetics Service, CHU Strasbourg, Strasbourg, France.
41
Department of Histology and Embryology, Faculty of Medicine, Near East University, Lefkoşa, Cyprus.
42
Department of Histology and Embryology, Faculty of Medicine, University of Uludag, Bursa, Turkey.
43
Department of Medical Genetics, Faculty of Medicine, University of Uludag, Bursa, Turkey.
44
Centre for Human Genetics, Université de Franche Comté, Besançon, France.
45
A Twist of Fate-ATS, Owasso, Oklahoma, USA.
46
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
47
Center For Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium. bert.callewaert@ugent.be.

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.

PMID:
29323665
DOI:
10.1038/gim.2017.253

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