Study on Aorta Disease Marfan Syndrome: A Meta-Analysis

Article / Research Article

Nutthanit Teantunyakij

The Prince Royal’s College 117 Kaeonawarat Rd, Tambon Chang Moi, Amphoe Mueang Chiang Mai, Chang Wat Chiang Mai 50000

*Corresponding author :

Nutthanit Teantunyakij
The Prince Royal’s College 117 Kaeonawarat Rd
Tambon Chang Moi
Amphoe Mueang Chiang Mai
Chang Wat Chiang Mai 50000
Submitted :3 July 2021 ; Published : 17 July 2021

Abstract

Objective: To study, and evaluate evidence information based on Aorta Disease Marfan Syndrome and also its treatment from published studies to develop a single synthesis of the results portraying the overall treatment effect.

Methods: We searched online databases for studies and used meta-analytic methods to analyze the data.
Results: Marfan syndrome is a pleiotropic connective tissue disease inherited as an autosomal dominant trait, due to mutations in the FBN1 gene encoding fibrillin 1. It is an important protein of the extracellular matrix that contributes to the final structure of a microfibril. Few cases displaying an autosomal recessive transmission are reported in the world. This disease is considered as a very dangerous one.
However, doctors and scientists are trying to look for a more efficient and best method to treat the disease fully.
Conclusion: Marfan syndrome is an inherited connective-tissue disorder that affects many organ systems, including the skeleton, lungs, eyes, heart and blood vessels. For people with Marfan syndrome, certain activities are thought to increase the risk of serious complications. In general, most people living with Marfan syndrome should exercise regularly through low-intensity, low-impact activities adapted to meet their specific needs. Many people with Marfan syndrome take a beta-blocker medication to reduce stress on the aorta. Some patients with Marfan syndrome take other blood-pressure medications, such as an angiotensin receptor blocker (ARB) or an angiotensin-converting enzyme (ACE) inhibitor. Hospital doctors, family physicians, physiotherapists, physical education teachers, sports coaches and those working in the fitness industry should be aware of the nature of Marfan syndrome and how it relates to exercise ability.

Introduction

Marfan syndrome is an inherited disorder that affects connective tissue — the fibers that support and anchor your organs and other structures in your body. Marfan syndrome most commonly affects the heart, eyes, blood vessels and skeleton.

People with Marfan syndrome are usually tall and thin with unusually long arms, legs, fingers and toes. The damage caused by Marfan syndrome can be mild or severe. If your aorta — the large blood vessel that carries blood from your heart to the rest of your body — is affected, the condition can become life-threatening.

Treatment usually includes medications to keep your blood pressure low to reduce the strain on your aorta. Regular monitoring to check for damage progression is vital. Many people with Marfan syndrome eventually require preventive surgery to repair the aorta.

The signs and symptoms of Marfan syndrome can vary greatly, even among members of the same family, because the disorder can affect so many different areas of the body. Some people experience only mild effects, but others develop life-threatening complications.
Marfan syndrome features may include:

  1. Tall and slender build,
  2. Disproportionately long arms, legs and fingers,
  3. A breastbone that protrudes outward or dips inward,
  4. A high, arched palate and crowded teeth,
  5. Heart murmurs,
  6. Extreme nearsightedness,
  7. An abnormally curved spine, and
  8. Flat feet.

Marfan syndrome affects men and women equally and occurs among all races and ethnic groups. Because it’s a genetic condition, the greatest risk factor for Marfan syndrome is having a parent with the disorder.
Because Marfan syndrome can affect almost any part of your body, it may cause a wide variety of complication such as:

  • Cardiovascular complications – Aortic aneurysm, Aortic dissection, and Valve malformations
  • Eye complications – Lens dislocation, Retinal problems, Early-onset glaucoma or cataracts
  • Skeletal complications – Marfan syndrome increases the risk of abnormal curves in the spine, such as scoliosis. It can also interfere with the normal development of the ribs, which can cause the breastbone to either protrude or appear sunken into the chest. Foot pain and low back pain are common with Marfan syndrome.
  • Complications of pregnancy – Marfan syndrome can weaken the walls of the aorta, the main artery that leaves the heart. During pregnancy, the heart pumps more blood than usual. This can put extra stress on the aorta, which increases the risk of a deadly dissection or rupture.
    In short, Marfan syndrome is a condition that affects the connective tissue. Connective tissue holds the body together and provides support to many structures throughout the body. In Marfan syndrome, the connective tissue is not normal. As a result, many body systems are affected, including the heart, blood vessels, bones, tendons, cartilage, eyes, nervous system, skin and lungs.

The Causes of Aorta Disease Marfan Syndrome
Marfan syndrome is caused by a defect in the gene that enables your body to produce a protein that helps give connective tissue its elasticity and strength.

Most people with Marfan syndrome inherit the abnormal gene from a parent who has the disorder. Each child of an affected parent has a 50-50 chance of inheriting the defective gene. In about 25% of the people who have Marfan syndrome, the abnormal gene comes from neither parent. In these cases, a new mutation develops spontaneously.
Marfan syndrome is caused by a defect in the gene that encodes the structure of fibrillin and the elastic fibers, a major component of connective tissue. This gene is called fibrillin-1 or FBN1.

In most cases, Marfan syndrome is inherited. The pattern is called “autosomal dominant,” meaning it occurs equally in men and women and can be inherited from just one parent with Marfan syndrome. People who have Marfan syndrome have a 50 percent chance of passing along the disorder to each of their children.

In 25 percent of cases, a new gene defect occurs due to an unknown cause. Marfan syndrome is also referred to as a “variable expression” genetic disorder, because not everyone with Marfan syndrome has the same symptoms to the same degree.

Marfan syndrome is present at birth. However, it may not be diagnosed until adolescence or young adulthood. Marfan syndrome is fairly common, affecting 1 in 10,000 to 20,000 people. It has been found in people of all races and ethnic backgrounds.

Marfan syndrome is based on a clinical diagnosis. A multidisciplinary approach is necessary to make the diagnosis because multiple organ systems must be assessed. Members of the team will assess the eyes, heart and blood vessels, spine and skeletal system.

A thorough history of symptoms and information about family members that may have had related problems are also necessary. Other tests, such as chest x-ray, electrocardiogram and echocardiogram will be used to evaluate changes in the heart and blood vessels, and detect heart rhythm problems.

If sections of the aorta are not able to be visualized through echocardiogram, or a dissection is already suspected, a transesophageal echo, magnetic resonance imaging, or computed tomography scan may be needed.
Often a CT or MRI is also needed to evaluate for something called dural ectasia. Dural ectasia is a bulging of the lining of the spinal column. It often does not cause any symptoms but it can be associated with back pain in some patients. Dural ectasia is a feature that helps to support the diagnosis of Marfan syndrome but it can also occur with other connective tissue disorders.

A blood test can be used to help diagnose Marfan syndrome. This blood test is highly specialized and looks for changes in FBN1, the gene that is responsible for most cases of Marfan syndrome.

Genetic counseling should accompany genetic testing because FBN1 testing is not always straightforward. Blood tests also can be used to help in the diagnosis of other genetic mutations, such as Loeys-Dietz syndrome, that cause physical findings similar to Marfan syndrome. Learn more about genetic counseling.

Treatment of Aorta Disease Marfan Syndrome
Treatment

Marfan syndrome requires a treatment plan that is individualized to the patient’s needs. Some people may not require any treatment, just regular follow-up appointments with their doctor. Others may need medications or surgery. The approach depends on the structures affected and the severity of the condition.

Lifestyle issues
Follow-up: Routine follow-up including cardio-vascular, eye, and skeletal exams, especially during the growing years. Your doctors will discuss the frequency of follow-up with you.

Activity: Activity guidelines vary, depending on the extent of the disease and symptoms. Most people with Marfan syndrome can participate in some type of physical and/or recreational activities. Those with dilation of the aorta will be asked to avoid high-intensity team sports, contact sports, and isometric exercises. Ask your cardiologist about activity guidelines for you.

Pregnancy: Genetic counseling should be performed prior to pregnancy as Marfan syndrome is an inherited condition. Pregnant women with Marfan syndrome are considered high risk cases. If the aorta is normal size, the risk for dissection is lower, but not absent. Those with even slight enlargement are at higher risk and the stress of pregnancy may cause more rapid dilation. Careful follow-up, with frequent blood pressure checks and monthly echocardiograms is required during pregnancy. If there is rapid enlargement or aortic regurgitation, bed rest or surgery may be required. Your doctor will discuss with you the best method of delivery with you.

Endocarditis prevention: People with Marfan syndrome who have also had valve surgery have an increased risk for bacterial endocarditis. This is an infection of the heart valves or tissue which occurs when bacteria enter the blood stream. To reduce the risk of endocarditis, antibiotics should be given prior to dental or surgical procedures in patients with Marfan syndrome who have had valve surgery. Check with your doctor about the type and amount of antibiotics you should take. A wallet card may be obtained from the American Heart Association (PDF) with specific antibiotic guidelines.

Medications
Medications are not used to treat Marfan syndrome, however, they may be used to prevent or control complications. Medications may include:

A beta-blocker improves the heart’s ability to relax, decreases the forcefulness of the heartbeat and the pressure within the arteries, thereby preventing or slowing the enlargement of the aorta. Beta-blocker therapy should begin at an early age.

In people who are unable to take beta-blockers due to asthma or side-effects, a calcium channel blocker, such as verapamil, is recommended.

An angiotensin receptor blocker is a type of medication that acts on a chemical pathway in the body. These agents are often used in treatment of high blood pressure as well as heart failure.
Clinical trials are currently being conducted to evaluate how these medications may prevent aortic enlargement. Early studies are encouraging.

Surgery
Surgery for Marfan syndrome is aimed at preventing aortic dissection or rupture and treating valve problems. When the aorta diameter is more than 4.7 cm to 5.0 cm, or if the aorta is enlarging at a rapid pace, surgery is recommended. Your cardiologist may also calculate your aortic root diameter to height ratio, since this may also influence whether you should have surgery. If you are contemplating a pregnancy then that would also affect the recommendations for surgery.

The recommendation for surgery is based on size of the aorta, expected normal size of the aorta, rate of aortic growth, age, height, gender and family history of aortic dissection. Surgery involves a replacement of the dilated portion of the aorta with a graft.

Valve repair or replacement surgery may be needed when Marfan syndrome causes a leaky aortic or mitral valve that leads to changes in the left ventricle or heart failure.

It is recommended that people with Marfan syndrome undergo surgery by surgeons at major centers who are experienced in this type of surgery. A better understanding of Marfan syndrome combined with earlier detection, careful follow-up and safer surgical techniques have resulted in better outcomes for patients.

Get more information on Aorta Surgery for Marfan Syndrome including: Aorta surgery, valve sparing re-implantation aorta surgery, and valve repair or replacement surgery for Marfan Syndrome.

Management

PRE-MANAGEMENT

  • Avoid direct skin to skin contact.
  • Avoid sports, competitive athletics, or isometric exercise.
  • Minimize unnecessary exposure.
  • Regular eye examinations are essential for identifying and correcting any vision problems associated with it.
  • Walk straight, avoid bending of spine.
  • Annual evaluations are important to detect any changes in the spine or sternum.
  • Suggest not to smoke.
  • While eating a balanced diet is important for maintaining a healthy lifestyle, no vitamin or dietary supplement has been shown to help cure, or prevent Marfan syndrome.

PRESENT MANAGEMENT

  • Eye examinations are essential for identifying and correcting any vision problems associated with it. In most cases, eyeglasses or contact lenses can correct the problem, although surgery may be necessary in some cases.
  • Checkups and echocardiograms help the doctor evaluate the size of the aorta and the way the heart is working. Those with heart problems are encouraged to wear a medical alert bracelet and to go to the emergency room if they experience chest, back, or abdominal pain.
  • Heart-valve problems can be managed with drugs such as beta-blockers, which may help decrease stress on the aorta.
  • The goal of treatment is to slow the progression of aortic dilation and damage to heart valves by eliminating arrythmias, minimizing the heart rate, and minimizing blood pressure. Beta blockers have been used to control arrythmias and slow the heart rate.
  • Surgery should be performed before the aorta reaches a size that puts it at high risk for tear or rupture. Because blood clots can form around artificial heart valves, people who have a valve replaced must take the blood-thinning drug for the rest of their lives.
  • Other medications might be needed to further minimize blood pressure without slowing the heart rate, such as ACE inhibitors and angiotensin II receptor antagonists, also known as angiotensin receptor blockers.
  • If the dilation of the aorta progresses to a significant diameter aneurysm, causes a dissection or a rupture, or leads to failure of the aortic or other valve, then surgery becomes necessary. New valve-sparing surgical techniques are becoming more common.
  • If Dural ectasia develops, medication may help minimize any associated pain.
  • While eating a balanced diet is important for maintaining a healthy lifestyle, no vitamin or dietary supplement has been shown to help cure, or prevent Marfan syndrome.
  • People with the syndrome should not engage in contact sports, competitive athletics, or isometric exercise.
  • Engaging in moderate aerobic exercise is important for promoting skeletal and cardiovascular health and a sense of well-being.
  • Marfan’s syndrome is passed on to offspring dominantly. This means that a child with one parent a bearer of the gene has a 50% probability of getting the syndrome.
  • The Nuss procedure is now being offered to people with Marfan syndrome to correct ‘sunken chest’.
  • Treatment of a spontaneous pneumothorax is dependent on the volume of air in the pleural space and the natural progression of the individual’s condition. A small pneumothorax might resolve without active treatment in one to two weeks. Recurrent pneumothoraxes might require chest surgery. Moderately sized pneumothoraxes might need chest drain management for several days in a hospital.
  • β Blocker treatment should be considered in any Marfan patient with aortic dilatation at any age, but prophylactic treatment may be more effective in those with an aortic diameter of < 4 cm • Risk factors for aortic dissection in Marfan syndrome include aortic diameter > 5 cm, aortic dilatation extending beyond the sinus of Valsalva, rapid rate of aortic dilatation, and family history of aortic dissection
  • Marfan patients of all ages should be offered at least annual evaluation with clinical history, examination, and transthoracic echocardiography. In children, serial transthoracic echocardiography at 6–12-month intervals are recommended, the frequency depending on the aortic diameter and the rate of increase
  • Marfan patients should be referred for prophylactic aortic root surgery when the diameter at the sinus of Valsalva exceeds 5.5 cm in an adult or 5.0 cm in a child.
  • Pregnant patients with Marfan syndrome are at increased risk of aortic dissection if the aortic diameter exceeds 4 cm. Such cases warrant frequent cardiovascular monitoring throughout pregnancy and into the puerperium.

FUTURE MANAGEMENT

  • Avoid sports, competitive athletics, or isometric exercise.
  • Avoid to smoke.
  • Take balanced diet.
  • Routine checkup.
  • Avoid junk food.
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