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Genetics Home Reference: your guide to understanding genetic conditions
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Arterial tortuosity syndrome

Reviewed January 2013

What is arterial tortuosity syndrome?

Arterial tortuosity syndrome is a disorder that affects connective tissue. Connective tissue provides strength and flexibility to structures throughout the body, including blood vessels, skin, joints, and the gastrointestinal tract.

As its name suggests, arterial tortuosity syndrome is characterized by blood vessel abnormalities, particularly abnormal twists and turns (tortuosity) of the blood vessels that carry blood from the heart to the rest of the body (the arteries). Tortuosity arises from abnormal elongation of the arteries; since the end points of the arteries are fixed, the extra length twists and curves. Other blood vessel abnormalities that may occur in this disorder include constriction (stenosis) and abnormal bulging (aneurysm) of vessels, as well as small clusters of enlarged blood vessels just under the skin (telangiectasia).

Complications resulting from the abnormal arteries can be life-threatening. Rupture of an aneurysm or sudden tearing (dissection) of the layers in an arterial wall can result in massive loss of blood from the circulatory system. Blockage of blood flow to vital organs such as the heart, lungs, or brain can lead to heart attacks, respiratory problems, and strokes. Stenosis of the arteries forces the heart to work harder to pump blood and may lead to heart failure. As a result of these complications, arterial tortuosity syndrome is often fatal in childhood, although some individuals with mild cases of the disorder live into adulthood.

Features of arterial tortuosity syndrome outside the circulatory system are caused by abnormal connective tissue in other parts of the body. These features include joints that are either loose and very flexible (hypermobile) or that have deformities limiting movement (contractures), and unusually soft and stretchable skin. Some affected individuals have long, slender fingers and toes (arachnodactyly); curvature of the spine (scoliosis); or a chest that is either sunken (pectus excavatum) or protruding (pectus carinatum). They may have protrusion of organs through gaps in muscles (hernias), elongation of the intestines, or pouches called diverticula in the intestinal walls.

People with arterial tortuosity syndrome often look older than their age and have distinctive facial features including a long, narrow face with droopy cheeks; eye openings that are narrowed (blepharophimosis) with outside corners that point downward (downslanting palpebral fissures); a beaked nose with soft cartilage; a high, arched roof of the mouth (palate); a small lower jaw (micrognathia); and large ears. The cornea, which is the clear front covering of the eye, may be cone-shaped and abnormally thin (keratoconus).

How common is arterial tortuosity syndrome?

Arterial tortuosity syndrome is a rare disorder; its prevalence is unknown. About 100 cases have been reported in the medical literature.

What genes are related to arterial tortuosity syndrome?

Arterial tortuosity syndrome is caused by mutations in the SLC2A10 gene. This gene provides instructions for making a protein called GLUT10. The level of GLUT10 appears to be involved in the regulation of a process called the transforming growth factor-beta (TGF-β) signaling pathway. This pathway is involved in cell growth and division (proliferation) and the process by which cells mature to carry out special functions (differentiation). The TGF-β signaling pathway is also involved in bone and blood vessel development and the formation of the extracellular matrix, an intricate lattice of proteins and other molecules that forms in the spaces between cells and defines the structure and properties of connective tissues.

SLC2A10 gene mutations that cause arterial tortuosity syndrome reduce or eliminate GLUT10 function. By mechanisms that are not well understood, a lack (deficiency) of functional GLUT10 protein leads to overactivity (upregulation) of TGF-β signaling. Excessive growth signaling results in elongation of the arteries, leading to tortuosity. Overactive TGF-β signaling also interferes with normal formation of the connective tissues in other parts of the body, leading to the additional signs and symptoms of arterial tortuosity syndrome.

Related Gene(s)

Changes in this gene are associated with arterial tortuosity syndrome.

  • SLC2A10

How do people inherit arterial tortuosity syndrome?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of arterial tortuosity syndrome?

These resources address the diagnosis or management of arterial tortuosity syndrome and may include treatment providers.

  • Genetic Testing Registry: Arterial tortuosity syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1859726)
  • Johns Hopkins McKusick-Nathans Institute of Genetic Medicine (http://www.hopkinschildrens.org/Arterial-Tortuosity-Syndrome-The-Case-of-a-Tortuos-Disorder.aspx)
  • National Heart, Lung, and Blood Institute: How is an Aneurysm Treated? (http://www.nhlbi.nih.gov/health/health-topics/topics/arm/treatment.html)

You might also find information on the diagnosis or management of arterial tortuosity syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/arterial-tortuosity-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/arterial-tortuosity-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about arterial tortuosity syndrome?

You may find the following resources about arterial tortuosity syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for arterial tortuosity syndrome?

  • arterial tortuosity
  • ATS

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about arterial tortuosity syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding arterial tortuosity syndrome?

aneurysm ; arachnodactyly ; arteries ; autosomal ; autosomal recessive ; blepharophimosis ; cartilage ; cell ; connective tissue ; cornea ; deficiency ; differentiation ; extracellular ; extracellular matrix ; gastrointestinal ; gene ; growth factor ; heart failure ; inherited ; keratoconus ; lower jaw ; micrognathia ; palate ; pectus excavatum ; prevalence ; proliferation ; protein ; recessive ; respiratory ; rupture ; scoliosis ; stenosis ; syndrome ; telangiectasia ; tissue ; tortuosity

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Akhurst RJ. A sweet link between TGFbeta and vascular disease? Nat Genet. 2006 Apr;38(4):400-1. (http://www.ncbi.nlm.nih.gov/pubmed/16570059?dopt=Abstract)
  • Callewaert BL, Willaert A, Kerstjens-Frederikse WS, De Backer J, Devriendt K, Albrecht B, Ramos-Arroyo MA, Doco-Fenzy M, Hennekam RC, Pyeritz RE, Krogmann ON, Gillessen-kaesbach G, Wakeling EL, Nik-zainal S, Francannet C, Mauran P, Booth C, Barrow M, Dekens R, Loeys BL, Coucke PJ, De Paepe AM. Arterial tortuosity syndrome: clinical and molecular findings in 12 newly identified families. Hum Mutat. 2008 Jan;29(1):150-8. (http://www.ncbi.nlm.nih.gov/pubmed/17935213?dopt=Abstract)
  • Castori M, Ritelli M, Zoppi N, Molisso L, Chiarelli N, Zaccagna F, Grammatico P, Colombi M. 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. Am J Med Genet A. 2012 May;158A(5):1164-9. doi: 10.1002/ajmg.a.35266. Epub 2012 Apr 9. (http://www.ncbi.nlm.nih.gov/pubmed/22488877?dopt=Abstract)
  • Coucke PJ, Willaert A, Wessels MW, Callewaert B, Zoppi N, De Backer J, Fox JE, Mancini GM, Kambouris M, Gardella R, Facchetti F, Willems PJ, Forsyth R, Dietz HC, Barlati S, Colombi M, Loeys B, De Paepe A. Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet. 2006 Apr;38(4):452-7. Epub 2006 Mar 19. (http://www.ncbi.nlm.nih.gov/pubmed/16550171?dopt=Abstract)
  • Ritelli M, Drera B, Vicchio M, Puppini G, Biban P, Pilati M, Prioli MA, Barlati S, Colombi M. Arterial tortuosity syndrome in two Italian paediatric patients. Orphanet J Rare Dis. 2009 Sep 25;4:20. doi: 10.1186/1750-1172-4-20. (http://www.ncbi.nlm.nih.gov/pubmed/19781076?dopt=Abstract)
  • Segade F. Glucose transporter 10 and arterial tortuosity syndrome: the vitamin C connection. FEBS Lett. 2010 Jul 16;584(14):2990-4. doi: 10.1016/j.febslet.2010.06.011. Epub 2010 Jun 12. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20547159?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2013
Published: October 27, 2014