Cardiovascular Risk in TS Patients: Integrating Cardiology, Genetics, and Endocrinology

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The importance of early cardiac evaluation and intervention for  those with Turner Syndrome (TS) cannot be stressed enough. In this post, we will explore a study that highlights the different cardiovascular risks for TS patients and their connection to endocrine and metabolic issues. Please note, that while individuals with TS are at a higher risk for cardiovascular issues, that risk can be mitigated with early and appropriate medical screening and intervention. For this reason, the Turner Syndrome Foundation (TSF) tirelessly advocates for early diagnosis and continued research. Everyone’s health is different, so please consult with your medical team, especially your cardiologist, regarding these risks.

Note: Please consult the glossary towards the end of this article for terms you may not be familiar with.

TS and Haploinsufficiency

TS is a chromosomal disorder that affects 1 in 2,000 live female births. It results from partial or complete loss of an X chromosome. About 50% of  TS patients in the U.S. have a 45 X0 karyotype (all cells have one missing X chromosome), 20–30% have mosaicism (45 X0/46 XX–some cells have only one X chromosome, and some cells have both X chromosomes). The remaining have X chromosome structural abnormalities. The X chromosome has many genes that code for various organs, like the heart, ovaries, immune system, skeletal system, and others. Loss of the entire or part of the X chromosome can lead to single copies of these genes, which may not be adequate to produce the needed gene product. This is called haploinsufficiency

Researchers Kristian H. Mortensen, from the Great Ormond Street Hospital for Children in London; Niels H. Andersen, from the University of Washington in Seattle; and Claus H. Gravholt, from Aarhus University Hospital in Denmark published a study called Cardiovascular Phenotype in Turner Syndrome—Integrating Cardiology, Genetics, and Endocrinology.

In the study, they describe that the SHOX gene has been shown to cause haploinsufficiency in TS, which can lead to cardiovascular disease. The X chromosome has 1,098 genes, far exceeding the

78 genes in the Y (male) chromosome. Morbidity and mortality are higher in undiagnosed TS patients than in the general population. Fortunately though, early diagnosis can help lower this risk.

Cardiovascular Phenotype in TS

Cardiovascular disease can be a critical characteristic of TS. It is responsible for half of the three-fold increased mortality in those with TS. This study focuses on TS associated cardiovascular morbidity and mortality. It also spotlights the importance of early diagnosis and subsequent standard care to reduce morbidity and mortality. The cardiovascular phenotype alone contributes 8% (congenital) and 41% (acquired) of all mortality in TS patients.

“Congenital or acquired cardiovascular diseases cause increased mortality and morbidity in TS patients. Improving their cardiovascular health through collaboration, research, awareness, and advocacy can improve their overall outcomes.”

Types of Cardiovascular Disease

The types of  cardiovascular disease associated with TS can be broadly categorized as congenital or acquired


The spectrum of congenital heart diseases spans from trivial defects to severe and highly complex disorders. From 22 to 70% of all TS patients have a form of congenital heart disease, including:

  • Bicuspid aortic valve: It occurs in 15 to 30% of TS patients, as compared with 1 to 2% of the general population. As the diagnostic sensitivity to differentiate between tricuspid (normal) and bicuspid valves has improved with the use of cardiac magnetic resonance imaging (MRI), the prevalence appears to be increasing. Aortic valve stenosis is seen in 4 to 16%, and regurgitation in 6 to 45% of TS patients.
  • Coarctation of the aorta: 17% of TS patients are known to have coarctation, as compared to 0.04% of the general population. Coarctation can be corrected surgically, but more research needs to be done on the best technique to do so.
  • Mild congenital heart defects: Associated cardiac lesions are among the mild congenital heart defects that can be found in TS patients. Other mild defects include: atrial septal defects, ventricular septal defects, partial anomalous pulmonary venous drainage, persistent left superior vena cava, persistent arterial duct, interrupted inferior vena cava with azygous continuation, and pulmonary valve stenosis.

Fetal ecocardiography ( ECG) performed in weeks 11 to 15 of pregnancy can detect some of the above-mentioned congenital heart defects. Most of them were in the 45 X0 karyotypes; however, lesions are seen in both 45 X0 and mosaic karyotypes.


There is an increased risk of acute aortic dissection in TS patients after the age of 20, stroke after 30, and myocardial infarction (heart attack) after 50.

Aortic dissection is known to occur in 1 to 2% of patients with TS. Peak incidents occur from the 30s to 50s. However, they are not restricted to just adulthood, with an increased incidence rate in the below-19 age group. The outcome of aortic dissection in TS patients is equally dangerous as in the general population, with 22 in 100 patients dying before reaching a hospital.

 In TS, the aortic dissection risk factors are hypertension; karyotype 45 X0; aortic dilation; and left-sided obstructive lesions

including bicuspid aortic valves, coarctation of the aorta, and other obstructive arch lesions.

Aortic diameter is the main risk indicator for aortic dissection. It is assessed by cardiac MRI. Young patients with TS have a smaller aortic diameter, and adults with TS a larger aortic diameter as compared with healthy peers. A larger aortic diameter increases the risk of aortic dissection in TS; however, there is no cut-off value.

The risk of aortic dissection in the pregnant TS population is as high as 2 in 100 pregnancies. Little information is available about causes for aortic dilation, dissection, and rupture. There are some concerns that recombinant human growth hormone (HGH) treatment and estrogen replacement therapy could induce unfavorable aortic wall changes. Patients and their parents should weigh carefully the benefits and risks of growth hormone therapy with their medical team.

Stroke risk increases after age 30, causing increased morbidity and mortality. The risk markers for stroke in TS patients include hypertension, insulin resistance, and obesity. These markers predispose patients to early aging. Atrial fibrillation (AFib) can also increase the risk of thromboembolic stroke in TS. Especially relevant to young TS patients, procoagulant disorders of the clotting system can lead to thromboembolic stroke.

Other Cardiovascular Diseases in TS Patients

Ischemic heart disease (related to narrowed arteries in the heart) is more frequent in TS patients. It increases mortality from age 50. TS patients of any age can have elevated blood pressure. Two factors that can induce high blood pressure are oral contraceptives and postmenopausal hormone. Patients should weigh carefully the benefits and risks of hormone replacement therapy with their medical team.

Some other causes of hypertension include insulin resistance, obesity, and GH deficiency or resistance. In TS patients, high blood pressure can contribute to aortic dilation and dissection. 

Sinus tachycardia is a lifelong phenomenon in TS. The risk of atrial tachycardia is high, with bradycardia rare.

Link Between Cardiovascular, Endocrine, and Metabolic Risk Factors

There is a link between cardiovascular, endocrine, and metabolic factors and how they affect patients with TS. Some of these factors are described below:

  • Growth hormone deficiency or resistance is the biggest cause of reduced final height in individuals with TS, specifically SHOX haploinsufficiency. 
  • Estrogen deficiency is also common in patients with TS. Estrogen replacement therapy, a common treatment for estrogen deficiency, may affect cardiovascular disease. 
  • Both type I and type II diabetes are common in patients with TS. 
  • Elevated liver enzymes are common in TS. Cirrhosis is five times more common in those with TS. The hepatic abnormalities could be because of the deficiency of hormones, such as beta-estradiol. Treatment with estrogen replacement therapy normalizes the liver enzymes.
  • X-chromosome material haploinsufficiency is known to cause autoimmune conditions (e.g., celiac disease, hypothyroidism/Hashimoto’s thyroiditis) in patients with TS.


  • Aortic dilation and dissection: An expansion of the aorta (the body’s main artery), which can lead to dissection and rupture, making it a potentially lethal disease. An aortic dissection is a serious condition in which a tear occurs in the inner layer of the aorta.
  • Aortic valve stenosis: Also called aortic stenosis, this occurs when the heart’s aortic valve narrows. The valve doesn’t open fully, which reduces or blocks blood flow from your heart into the main artery in the body (aorta) and to the rest of the body.
  • Atrial fibrillation: Commonly known as AFib, it is the most common type of irregular heartbeat that often causes the heart to beat too quickly. One of the biggest concerns with AFib is the risk of stroke.
  • Autoimmune condition/disease: Happens when the body’s natural defense system can’t tell the difference between your own cells and foreign cells, causing the body to mistakenly attack normal cells.
  • Bicuspid aortic valve: An aortic valve with only two cusps (or flaps) instead of three. The aortic valve controls the flow of blood from the left ventricle (chamber) to the aorta, the main artery delivering blood to the rest of the body.
  • Cardiac lesions: atypical tissue or scarring in the heart.
  • Cardiovascular phenotype: The observable structural and physiological characteristics of the heart, blood vessels, or circulatory system.
  • Cerebrovascular disease: A group of conditions that affect blood flow in the blood vessels in the brain.
  • Cirrhosis: A chronic disease of the liver marked by degeneration of cells, inflammation, and fibrous thickening of tissue.
  • Coarctation: Congenital narrowing of a short section of the aorta.
  • Congenital heart disease: A general term for a range of birth defects that affect the normal way the heart works. The term “congenital” means the condition is present from birth. 
  • Fetal ECG: Fetal echocardiography is a test similar to an ultrasound. This exam allows your doctor to better see the structure and function of the fetus’ heart.
  • Haploinsufficiency: The situation that occurs when one copy of a gene is inactivated or deleted, and the remaining functional copy of the gene is not adequate to produce the needed gene product to preserve normal function.
  • Morbidity: the condition of suffering from a disease or medical condition.
  • Mortality: the state of being dead or subject to death.
  • Procoagulant disorders: A blood disorder involving the factors that help the blood clot.
  • SHOX gene: This gene provides instructions for making a protein that regulates the activity of other genes.
  • Sinus tachycardia: A type of irregular heartbeat characterized by a faster-than-normal heart rate.
  • Thromboembolic stroke: A stroke caused by a blood clot traveling to the brain or from the brain to another part of the body.

What You Can Do

Patient, Parents, and Caregivers

Individuals with TS have a high risk of congenital and acquired heart diseases, diabetes, metabolic disorders, and autoimmune diseases. But they can live long, fulfilling lives.

It is important to work with a multidisciplinary care team that involves a team of specialists, including a:

  • geneticist (gene specialist);
  • endocrinologist (hormone specialist);
  • cardiologist (heart specialist);
  • gastroenterologist (gastrointestinal specialist);
  • ENT (ear, nose, and throat specialist);
  • hepatologist (liver specialist); and/or 
  • nephrologist (kidney specialist).

Please see the Guidelines & Resources on TSF’s website for additional information about medical care.

Medical Professionals

TSF continues to fight for early diagnosis and increased TS research. You can help us by:

If you are a medical provider, we encourage you to::

Written by Ruchika Srivastava, volunteer blog writer. Edited by Susan Herman, TSF Blog Coordinator, and Kayla Ganger, PA-C, TSF Professional Membership Liaison 

© Turner Syndrome Foundation, 2022

One Comment on “Cardiovascular Risk in TS Patients: Integrating Cardiology, Genetics, and Endocrinology

  1. Cardiovascular risk refers to the probability or likelihood of developing cardiovascular diseases (CVDs) in an individual over a certain period of time. It is influenced by various factors that can increase or decrease an individual’s chances of developing CVDs. Understanding and assessing cardiovascular risk is crucial for preventive measures, early detection, and appropriate management of CVDs.

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