Arterial Tortuosity Syndrome

Arterial tortuosity syndrome is a rare genetic disorder that causes blood vessels to become twisted, elongated, and prone to serious complications that can affect the heart, brain, and other vital organs.

Table of contents

• What is Arterial Tortuosity Syndrome?
• Medical Classification Codes
• Other Names
• How Common Is This Condition?
• Genetic Cause
• How Is It Inherited?
• Signs and Symptoms
• Serious Complications
• How Is It Diagnosed?
• Treatment and Management
• Regular Health Monitoring
• Outlook and Lifespan

What is Arterial Tortuosity Syndrome?

Arterial tortuosity syndrome is a disorder that affects connective tissue, which is the material in the body that provides strength and flexibility to structures such as blood vessels, skin, joints, and the digestive system.^[1]

The name of this condition describes its main feature: abnormal twists and turns, called tortuosity, in the blood vessels that carry blood from the heart to the rest of the body. These vessels are called arteries. The tortuosity happens because the arteries become abnormally long. Since the end points of the arteries are fixed in place, the extra length causes the vessels to twist and curve.^[1]

This condition affects major and medium-sized arteries throughout the body, including the aorta, which is the largest artery that carries blood away from the heart.^[2] Along with the twisting, other blood vessel problems can occur, such as narrowing of vessels (called stenosis), abnormal bulging (called aneurysms), and small clusters of enlarged blood vessels just under the skin.^[1]

Medical Classification Codes

208050
Q27.8; Q87.82
C565942

Other Names

ATS, ATORS, Arterial Tortuosity

How Common Is This Condition?

Arterial tortuosity syndrome is extremely rare. About 100 cases have been reported in medical literature worldwide.^[1][4] The exact number of people affected is unknown, and the condition occurs equally in males and females.^[4]

Genetic Cause

Arterial tortuosity syndrome is caused by changes, called mutations, in a gene named SLC2A10. This gene is located on chromosome 20.^[1][3] At least 23 different mutations in this gene have been found in people with the condition.^[3]

The SLC2A10 gene provides instructions for making a protein called GLUT10. This protein appears to be involved in regulating an important process in the body called the transforming growth factor-beta (TGF-β) signaling pathway. This pathway controls how cells grow and divide, how they mature to perform specific jobs, and how bones and blood vessels develop.^[1]

When the SLC2A10 gene has mutations, the GLUT10 protein does not work properly or is completely absent. This leads to too much activity in the TGF-β signaling pathway. The excessive growth signals cause the arteries to become too long, which creates the twisting pattern. The overactive signaling also disrupts the normal structure of connective tissue throughout the body, leading to problems beyond the blood vessels.^[1]

How Is It Inherited?

Arterial tortuosity syndrome follows an autosomal recessive pattern of inheritance.^[2][4] This means that a person must inherit two copies of the mutated gene—one from each parent—to develop the condition.

Parents who each carry one mutated copy of the gene typically do not show any signs of the disorder themselves. When both parents are carriers, each of their children has a 25 percent chance of having the condition, a 50 percent chance of being a carrier like the parents, and a 25 percent chance of not inheriting the mutation at all.

Signs and Symptoms

The symptoms of arterial tortuosity syndrome are variable and depend on which arteries are affected. The condition usually begins to show signs in infancy or early childhood.^[4]

Blood Vessel Problems

The cardiovascular system is the main area affected by this condition. Blood vessel abnormalities may include:

• Tortuosity and elongation of major and medium-sized arteries^[3]
• Stenosis or narrowing of arteries^[3]
• Aneurysms or abnormal bulging of arteries^[3]
• Problems with the aortic valve^[3]
• High blood pressure (hypertension)^[3]
• Enlargement of the heart due to increased pressure^[7]

Facial Features

People with arterial tortuosity syndrome often have distinctive facial features, which may include:

• A long, narrow face with sagging or droopy cheeks^[1]
• Eye openings that are narrowed (called blepharophimosis) with outside corners that point downward^[1]
• A beaked nose with soft cartilage^[1]
• A high, arched roof of the mouth^[1]
• A small lower jaw (called micrognathia)^[1]
• Large ears^[1]

Many people with this condition appear older than their actual age.^[1]

Skin and Joint Problems

Because connective tissue throughout the body is affected, people may experience:

• Unusually soft and stretchy skin^[1]
• Joints that are either very loose and flexible (called hypermobile) or have deformities that limit movement (called contractures)^[1][2]

Skeletal Features

Skeletal abnormalities may include:

• Long, slender fingers and toes (called arachnodactyly)^[1]
• Curvature of the spine (called scoliosis)^[1]
• A chest that is either sunken inward (called pectus excavatum) or protruding outward (called pectus carinatum)^[1]

Other Problems

Additional features may include:

• Protrusion of organs through gaps in muscles, known as hernias, which can occur in the groin (inguinal), diaphragm, or around the navel (umbilical)^[1][2]
• Elongation of the intestines^[1]
• Pouches called diverticula in the intestinal walls^[1]
• Eye problems, including a cone-shaped and abnormally thin cornea (called keratoconus)^[1]

Serious Complications

Complications from the abnormal arteries can be life-threatening. The cardiovascular system is the major source of illness and death in people with arterial tortuosity syndrome.^[2]

Dangerous complications can occur at any age and include:

• Rupture of an aneurysm, which causes massive blood loss from the circulatory system^[1]
• Sudden tearing of the layers in an arterial wall (called dissection), which also results in severe bleeding^[1][2]
• Blockage of blood flow to vital organs such as the heart, lungs, or brain, which can cause heart attacks, breathing problems, and strokes^[1]
• Heart failure because the narrowing of arteries forces the heart to work much harder to pump blood^[1]
• Stroke that is not caused by bleeding but by blockage of blood vessels to the brain^[2]
• Damage to abdominal organs from blocked blood flow^[2]

Because of these serious complications, arterial tortuosity syndrome has historically been fatal in childhood. However, some people with milder forms of the condition do live into adulthood.^[1] More recent data suggests that the mortality rate may be around 12 percent.^[3]

How Is It Diagnosed?

The diagnosis of arterial tortuosity syndrome requires two key findings: widespread arterial tortuosity seen on imaging tests and confirmation through genetic testing that shows mutations in both copies of the SLC2A10 gene.^[2][3]

Imaging Tests

Several imaging methods can be used to identify the twisted and elongated arteries:

• Echocardiography uses sound waves to create pictures of the heart^[2][3]
• CT scan (computed tomography) uses X-rays to create detailed three-dimensional images^[3][4]
• MRI (magnetic resonance imaging) or MRA (magnetic resonance angiography) uses magnets and radio waves to create detailed pictures of blood vessels^[2][3]
• Angiography involves injecting a special dye into blood vessels to make them visible on X-ray images^[3]

Genetic Testing

Genetic testing to find mutations in the SLC2A10 gene confirms the diagnosis and allows doctors to provide proper genetic counseling to families.^[4]

Other Tests

In some cases, doctors may examine tissue samples from blood vessel walls. Under the microscope, these samples show disruption and fragmentation of the elastic fibers in the arterial wall.^[4]

Treatment and Management

There is no cure for arterial tortuosity syndrome, but treatments can help manage symptoms and reduce the risk of serious complications. People with this condition benefit from coordinated care by a team of specialists at a medical center familiar with the disorder.^[2][3]

Medications

Medications may be used to reduce stress on arterial walls by lowering blood pressure. These include:

• Beta-adrenergic blockers (also called beta-blockers)^[2]
• Angiotensin-converting enzyme inhibitors (ACE inhibitors)^[2]
• Angiotensin II receptor antagonists, such as losartan^[2]

However, the effectiveness of these medications has not been fully established in arterial tortuosity syndrome. Doctors must be careful when using blood pressure-lowering medications if a person has narrowed arteries, especially in the kidneys, as these medications could cause kidney failure.^[2]

Surgery

Surgical procedures may be needed to treat aneurysms and severely narrowed arteries. When possible, surgeons may perform valve-sparing procedures to avoid the need for long-term blood-thinning medications.^[2] In some cases, procedures using catheters (thin tubes inserted into blood vessels) can be performed instead of open surgery.^[2]

Because wound healing may be delayed after surgery, special care is needed. Stitches should be placed carefully without tension and should remain in place for about ten days. When repairing hernias, surgeons may use a supporting mesh to reduce the chance of the hernia coming back.^[2]

Management of Other Problems

• Skeletal problems such as scoliosis require care from an orthopedic specialist^[2]
• Eye problems should be managed by an eye doctor (ophthalmologist) with expertise in connective tissue disorders^[2]
• Dental crowding may need attention from an orthodontist^[2]

Lifestyle Considerations

People with arterial tortuosity syndrome can and should maintain moderate aerobic activity, such as swimming. However, they should avoid activities that put too much stress on the cardiovascular system. Psychological support may be helpful, especially during adolescence.^[2]

Regular Health Monitoring

Regular monitoring is essential to detect problems early. Recommended surveillance includes:^[2]

• Echocardiography every three months until age five years
• MRA or CT scan with three-dimensional reconstruction from head to pelvis once a year, starting at birth or at the time of diagnosis
• Blood pressure monitoring at every medical visit
• Regular X-rays to check for progression of scoliosis, especially during periods of rapid growth
• Dental evaluations to check for tooth crowding as permanent teeth come in

Outlook and Lifespan

The outlook for people with arterial tortuosity syndrome varies depending on the severity of the condition. Early reports suggested high mortality rates, but more recent information indicates that about 12 percent of people with the condition may die from complications.^[3]

While the condition has often been fatal in childhood due to serious cardiovascular complications, some individuals with milder cases have survived into adulthood.^[1] The cardiovascular system remains the major source of health problems and the main concern for survival, with risks for aneurysm formation, arterial dissection, and stroke present at any age.^[2]

With improved diagnosis, regular monitoring, and advances in treatment, the prognosis for people with arterial tortuosity syndrome continues to improve. Early diagnosis and careful management by experienced medical teams are crucial for the best possible outcomes.