Introduction

Marfan syndrome is a genetic disorder that most people receive from their parents. This disease causes mutation(changes) to a specific gene that leads to problems with developing connective tissue, which supports your body's bones, muscles, organs and tissues.¹ About one-fourth of people with Marfan syndrome are not affected by their parents and they are the first person in their family who have this condition; it is called the "dominant" mode of inheritance. Symptoms of Marfan syndrome can vary from mild to severe as per the area of the body involved like skeleton, eyes, heart, blood vessels, skin, lungs etc. Treatment also varies depending on the location of the body affected.² 

What happens in marfan syndrome?

Every human has fibrillin-1 protein, which helps in the production of elastic fibres in connective tissue and also affects another protein in your body, transforming growth factor-beta (TGF-beta), which controls the functioning of cells throughout the body.³ Marfan syndrome leads to a genetic mutation that changes the amount of fibrillin-1 and the function of cells, which ultimately affects the strength and performance of tissues throughout the body. Which results in the overgrowth of bones, making them longer than usual.¹ 

Signs and symptoms

As Marfan syndrome affects your connective tissues, in some cases symptoms become visible at a very early stage, but in most cases, changes become evident as you age. Because connective tissues are widely present in your body, it can affect the entire body including your skeletal system, heart, blood vessels, eyes, skin and organs.⁴

Physical appearance

Physical symptoms include:⁴

• Longer arms, legs, fingers and toes concerning the rest of the body
• Long, narrow face
• Tall and thin body build
• Loose joints
• Flat feet
• Abnormal chest wall, with sternum, either caving inward or protruding outward
• Pain in the lower back and numbness in the legs
• Pain in the spinal cord due to weakness in the tissues that surround it. Curved spine (Scoliosis) affects 60% of people with Marfan syndrome

Eye problems

Eye problems are experienced by over half of individuals diagnosed with Marfan syndrome, which include:

• Glaucoma
• A difference in the shape of the eye
• Changes in vision result in blurry vision and nearsightedness
• The lens of the eyes develops cloudy areas or shifts, which develop cataracts and ectopia lentis respectively

Lung problems 

Changes in connective tissues of the lungs increase the chances of:

• Asthma
• Bronchitis
• Pneumonia
• Chronic obstructive pulmonary disease (COPD)

Dental issues

Dental problems include:

• Crowded teeth
• The arched palate (roof of the mouth) is narrow and higher than the normal

Skin problems

• Skin loses its elasticity, which leads to the development of stretch marks

Heart and blood vessel-related conditions

Most people with Marfan syndrome develop changes in their heart and blood vessels including:

• Aortic aneurysm. The wall of the aorta becomes weak and could burst. Mostly happens at the aortic root
• Aortic dissection. In this condition, initially, the inner layer of the three wall layers of the aorta gets torn, which leads to separation from other layers and possibly wall rupture
• Heart valve problems. In Marfan syndrome value tissues become weak, which causes leaking backflow of blood
• Arrhythmia. Changes in connective tissues of the heart lead to shortness of breath
• Irregular heartbeat like fluttering, rapid or forceful beats

Importance of treatment options

People with Marfan syndrome have nearly the same life expectancy as normal individuals, so treatment makes it possible for people with the disorder to have long and productive lives. Marfan syndrome symptoms vary from person to person, so everyone with Marfan syndrome must be treated as per the individual requirements.¹ If anyone diagnosed with Marfan syndrome preferably reaches a doctor having experience in treating Marfan syndrome, the doctor will keep close tabs on all the systems of the body which are vulnerable to developing problems. It includes regular eye exams, image tests for heart and lung problems, and an evaluation of your skeleton and growth. Ask your doctors how often you should schedule follow-up visits.⁵ 

Psychological support 

If you are experiencing the symptoms of Marfan syndrome talk to your family and friends and discuss the problems you are facing. You can also join a community or online support. They may be able to put you in touch with a support group through the Marfan Trust. If it affects your body in such a way, which makes you feel depressed and anxious, you can get the help of a healthcare professional. 

Skeletal problems 

In Marfan syndrome, people have pain in and around their joints mostly in the hips. In such cases, moderate exercise, as well as pain relief like non-steroidal anti-inflammatory drugs (NSAIDs), can prove helpful. Treatment of curvature of the spine (scoliosis) will depend on the severity of the condition. Braces and physical therapies are enough to correct the curvature of the spine. However, for extreme scoliosis, surgery is required to prevent progression and to return the spine to its correct shape. Sometimes the natural position of the chest affected in Marfan syndrome results in a concave chest if it caves inwards and a convex chest if it protrudes outwards. In rare cases, if it presses against their lungs and affects breathing, surgery will be required. If skeletal problems are making it difficult for you to get around, physiotherapy may help make moving easier and more comfortable.⁶

Eye-related problems 

Marfan syndrome-related eye problems are potentially serious and can lead to a permanent loss of vision. Marfan-related eye complications can be quickly diagnosed during an annual visit to an ophthalmologist. Most eye-related problems can be corrected by the use of eyeglasses and contact lenses, in some cases, surgery may also be required. If you develop cataracts as a result of Marfan syndrome, you may require surgery to remove the clouded lens. In Marfan syndrome, people have a higher risk of developing glaucoma. Although glaucoma cannot be cured, it is possible to prevent it from getting worse. Treatment options include eye drops, laser treatment or surgery.⁵

Heart-related problems

Medications like beta-blockers and angiotensin II receptor blockers are prescribed alone or in combination to slow heart rate, reduce the force of contractions, and decrease the rate of aortic root enlargement thus lowering the strain on the heart and reducing the risk of widening and tearing of the aorta. Regular monitoring of heart valves and aorta with echocardiograms, to find valve-related problems and widening at the root of the aorta, which can be treated by surgically replacing a damaged section.⁵ 

Lifestyle modifications

Eat a healthy and balanced diet rich in fruits, vegetables and whole grains. Quit smoking, because it hurts both your bone and lung health. Exercise should be limited to less intense activities, which can be done at your own pace like walking, cycling or jogging. 

Recommended to avoid competitive or contact sports. Stretching of the connective tissue in the cardiovascular system should be limited. Food and medications which tend to increase blood pressure should be avoided.⁶ 

Pregnancy

If you are thinking about getting pregnant, discuss it with your doctor. Although pregnancy can add stress to the heart, planning helps doctors treat problems before the pregnancy to keep both the mother and baby safe and healthy. 

Genetic counseling

Marfan syndrome is a genetic disorder caused by alteration (changes) in a specific gene called  FBN1, which helps make up the body's connective tissue which supports and regulates the growth of different body parts. So alteration in FBN1 does not allow connective tissue to work normally.⁷

Although clinical diagnosis of Marfan syndrome is possible, genetic testing of the FBN1 gene is important. As some symptoms of Marfan syndrome may develop with age and the symptoms do not meet the criteria of clinical diagnosis, genetic testing can be helpful at this stage. If anyone is found to have an FBN1 gene disease-causing variant should visit a cardiologist and ophthalmologist once a year. Annual checkups help the doctor monitor and evaluate the condition of body parts like the heart, blood vessels, and eyes. So if any problem presents, be managed with medications at the early stage otherwise surgery may be recommended.⁸

New developments

The old belief was that people with Marfan's syndrome were born with weak tissues, making them prone to problems later in life. It was tough to think of ways to strengthen these tissues.⁸ However, the new understanding is that the issues in Marfan's syndrome develop after birth, and they might be more about problems in how the body regulates its tissues rather than just weak tissues. Except for one symptom, most of the problems in Marfan's seem to involve issues with a molecule called TGF β. Recent studies on mice suggest that we might be able to fix these problems even after birth by changing how TGF β works, possibly using drugs that are already being developed for other conditions. These treatments could not only help with heart issues but also with other problems caused by Marfan's syndrome.²

Summary 

Marfan syndrome, a rare hereditary connective tissue disorder, impacts various body systems and can lead to significant health complications if left untreated. Diagnosis relies on the revised Ghent nosology, which involves a thorough assessment of systemic manifestations. Although primarily diagnosed clinically, genetic testing may be beneficial in certain cases. While the exact cause is not fully understood, mutations in the fibrillin-1 gene are thought to contribute to abnormal TGF-β signalling. Cardiovascular issues, such as aortic root dilation and mitral valve prolapse, pose the greatest risk, with acute aortic dissection being a major concern. Routine monitoring of cardiovascular, ocular, and skeletal health through echocardiography, eye examinations, and MRI is recommended post-diagnosis or following surgery. Recent insights into the genetic and molecular aspects of the condition have expanded our understanding beyond its traditional classification as a structural connective tissue disorder.