Arterial tortuosity syndrome: 40 new families and literature review

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aorta / diagnostic imaging
  • Aorta / physiopathology
  • Arteries / abnormalities*
  • Arteries / diagnostic imaging
  • Arteries / physiopathology
  • Biopsy
  • Child
  • Child, Preschool
  • Connective Tissue Growth Factor / genetics
  • Female
  • Glucose Transport Proteins, Facilitative / genetics*
  • Hernia, Diaphragmatic / genetics*
  • Hernia, Diaphragmatic / physiopathology
  • Humans
  • Infant
  • Joint Instability / epidemiology
  • Joint Instability / genetics*
  • Joint Instability / physiopathology
  • Male
  • Mutation
  • Pedigree
  • Respiratory Distress Syndrome, Newborn / genetics*
  • Respiratory Distress Syndrome, Newborn / physiopathology
  • Skin / pathology
  • Skin Diseases, Genetic / epidemiology
  • Skin Diseases, Genetic / genetics*
  • Skin Diseases, Genetic / physiopathology
  • Smad2 Protein / genetics
  • Transforming Growth Factor beta / genetics
  • Vascular Malformations / epidemiology
  • Vascular Malformations / genetics*
  • Vascular Malformations / physiopathology


  • CCN2 protein, human
  • Glucose Transport Proteins, Facilitative
  • SLC2A10 protein, human
  • SMAD2 protein, human
  • Smad2 Protein
  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor

Supplementary concepts

  • Arterial Tortuosity Syndrome
  • Respiratory Distress Syndrome In Premature Infants