Connective tissues (CT) join and separate different organs and tissues in the body. They are found in the body including CNS i.e. Central Nervous System and also meninges which is the outer layer of central nervous system is made of these connective tissues. They are made up of proteins.
Connective tissues consist of cells, extrafibrillar matrix and fibres. The cells of CT include leucocytes, fibroblasts, mast cells, macrophages and adipocytes. A genetic disorder that affects the connective tissues is called Marfan syndrome.
Marfan syndrome was first described in 1896 and is named after Antoine Marfan. Marfan syndrome was described as an autosomal dominant disorder.
What is Marfan Syndrome?
An inherent disorder that affects the connective tissues in the body is called Marfan syndrome. Marfan syndrome is caused by the proteins in the connective tissues.
The mutation of fibrillin-1 protein increases the TGF-β i.e. transforming growth factor beta protein, which disrupts the functioning of connective tissues. This leads to Marfan syndrome and some associated disorders.
Marfan syndrome can affect various parts of the body including eyes, blood vessels, heart, bones, joints, lungs, skin etc. In U.S., 1 in 5000 people is affected from this disorder.
Marfan syndrome can disrupt the functioning of aorta, an artery that supplies blood from the heart to the body. The inner layer of aorta may get ruptured causing bleeding in the vessel, which may be lethal.
Signs and Symptoms of Marfan Syndrome
Marfan syndrome may not show immediate signs or symptoms. They may develop at any age and may get worse. However, they may vary from person to person. The signs and symptoms of Marfan Syndrome include:
- Disproportionately long legs, arms, toes and fingers
- Extremely tall and slender build
- Long, narrow face
- High arched neck and crowded teeth
- Indented or protruding sternum (breastbone)
- Dislocated lenses of the eyes
- High pressure in the eye i.e. glaucoma
- Cystic changes in the lungs
- Flexible joints
- Flat feet
- Curved spine
- Abnormal heart sounds
Other symptoms of Marfan Syndrome include:
- Learning disability
- Small lower jaw i.e. micrognathia
- Stretch marks on the skin which are not associated with weight loss.
Prognosis and Life Expectancy of Marfan Syndrome
The average life expectancy of a person with Marfan syndrome is 45 years, if it is untreated. However, with proper care there can be normal life expectancy.
Epidemiology of Marfan Syndrome
The occurrence of Marfan syndrome is estimated to be 1 in 5,000 in the US. In Europe, it is estimated to be 3 in 10,000. The prevalence of the disorder is thought to be similar globally.
Causes of Marfan Syndrome
The cause of Marfan syndrome is a defective gene that equips the body in producing proteins, which helps in strengthening and increasing elasticity in connective tissues. The causes vary in different cases as the gene affects in different ways in different patients, which is called variable expression. Hence, the causes of Marfan Syndrome can be divided as under:
- The gene is generally inherited from the parent having Marfan syndrome. There is a 50-50 chance for the child to get affected by the inherited defective gene.
- 25% cases are a result of unconstrained mutation at the time of conception.
- In rare instances, the gene defect can occur during egg cells or sperm formation.
The reason behind the variable expression of the gene in Marfan syndrome is not yet understood and is being studied by the scientists.
Pathophysiology of Marfan Syndrome
The mutation in FBN1 gene on chromosome 15 leads to Marfan syndrome. The mutation of FBN1 gene encodes a glycoprotein called fibrillin-1, which affects the strength and elasticity of connective tissues in the body.
Transforming growth factor beta i.e. TGF- β plays a vital role in Marfan syndrome. It binds directly to fibrillin-1 which disables the biological activity. This binding results into an inflammatory reaction which releases proteases that degrades the elasticity and strength of connective tissues.
How is Marfan Syndrome Inherited?
There are two copies of fibrillin gene in everybody. The mutation in any one gene leads to Marfan syndrome in people. The normal copy of fibrillin has inadequate potential to compensate the activity of the mutate gene. Thus, at the time of conception either the mutate fibrillin or normal fibrillin is passed to the child from either of the parents. Hence, there is a 50-50% chance of transmitting the mutate fibrillin gene from the parent with Marfan syndrome to the child. However, the mutation may take place during the formation of sperm or egg cell, resulting into transmission of mutate fibrillin gene. Thus, the parents may not have Marfan syndrome, but the child may get affected and may pass to next generation.
Diagnosis of Marfan Syndrome
The diagnosis of Marfan syndrome is not easy as it may develop at any age. However, a careful examination by a team of specialist doctors can help in diagnosing Marfan syndrome. The family history of Marfan syndrome is an important tool in identifying Marfan syndrome. The clinical diagnosis includes:
- Echocardiogram: It is a tool to measure the heart murmur.
- Ghent Nosology:It is a criterion developed in 1988 and revised in 1996 that defines the clinical features in pulmonary, ocular, skeletal, cardiovascular and integumentary systems. This helps in diagnosing the symptoms of Marfan syndrome. It includes:
- Steinberg Thumb Sign or Walker- Murdoch Wrist Sign: Arachnodactyly, in the skeletal system may be assessed using these two techniques. Steinberg Thumb sign is a sign where the entire thumbnail reaches the ulnar border of hand. Whereas, Walker-Murdoch Wrist sign is a sign in which the thumb and fifth finger overlaps the wrist. These two signs help in identifying the Marfan syndrome by measuring the upper to lower segment ratios. If the diagnosis is positive then Pelvic X-ray can be undertaken.
- Lens Dislocation: It helps in identifying changes in the ocular system. Also, myopia which is related to eye movement can be a criterion in identifying Marfan syndrome.
- Aortic Dilation: It is a major criterion in cardiovascular system as it helps in identifying the diameter of the aorta at the sinus of Valsalva. The measured values should be compared to the normal values according to body surface and age of the patients.
- Pelvic X-ray: It can be undertaken to identify protrusio acetabulae, scoliosis or dural ectasia in the skeletal system.
Treatment & Management of Marfan Syndrome
The management of Marfan syndrome can be done as under:
- Surgical Management of Marfan Syndrome:Various surgeries can help in treating the associated symptoms in different systems. These include:
- Aortic Root Dilation: Aortic dilation helps in minimizing the chances of emergency consequences of Marfan syndrome. β-blocker treatment can be undertaken in patients who underwent aortic root dilation.
- Prophylactic Surgery: It is an effective surgery if the aortic diameter is > 4 cm. Survival data shows an effective improvement in patients who underwent prophylactic surgery.
- Bentall Composite Graft Repair: In this surgery, the cardiothoracic surgeons would replace the aortic valve and aortic root. However, this has low operative mortality rate.
- Re-implantation Technique: This technique, described by David and Feindell in 1992, is an alternative valve conserving procedure, in which the aortic valve is re-implanted into a Dacron tube.However, these techniques are controversial as the aortic valve may require valve replacement through reoperation later.
- Lifestyle Changes for Marfan Syndrome: The patients with Marfan syndrome need to avoid competitive sports as they are at a higher risk of aortic rupture or dissection. Intense activities like weightlifting should be avoided. Brisk walking, doubles tennis, bowling or golf are less intensive activities and can be undertaken.
Coping with Marfan Syndrome
Coping with Marfan syndrome maybe difficult as it is a genetic disorder and it affects adults as well as their children. The adult who may discover Marfan syndrome later in life, would be disturbed as they would wonder how it would affect their relationships, careers and if their children would get affected or not.
Young adults suffering from Marfan syndrome may get self-conscious about their appearance, motor skills and academic performances. Hence, some cosmetic concerns as well as emotional problems are to be addressed by the parents, medical professional and teachers. Medical care and social support can help in coping with Marfan Syndrome for both the adults and children.
Famous People with Marfan Syndrome
Famous people who had Marfan syndrome include:
- Tutankhamen: Tutankhamen was an Egyptian Pharaoh who died at the age of 19. He began ruling his country at the age of 10. In the year 2007, several mummies were studied including Tutankhamen. He was discovered with Marfan syndrome with his unusual tall and thin body and a mild curve in the spine.
- Julius Ceaser: A great ruler and dictator, Julius Ceaser showed symptoms of Marfan syndrome with his long fingers and the long and skinny body.
- Bradford Cox: Bradford Cox known for his multiple talents as a lyricist, singer, guitarist and an actor was diagnosed with Marfan syndrome around 10-12 years of age. This made him have few friends and music was his only refuge.
- Jonathan Larson: A composer and playwright, Jonathan Larson's career was short due to his sudden death. The diagnosis of Marfan syndrome wasn't done and the cause of death was found to be a dissection in the aorta.
- Abraham Lincoln: The long head, thin nose and a not-so-wide chest with lean stature of the 16th President of U.S. are symptoms of Marfan syndrome. His descendants are rumored to inherit the gene, however there is no evidence.
- Flo Hyman: An Olympic silver medalist and a volley ball player, Flo Hyman was tall, which she used to her advantage. She died on January 24, 1986 during a game in Japan. Later she was discovered to have Marfan syndrome.
- Osama Bin Laden: Osama Bin Laden showed symptoms of Marfan syndrome through his long bony face and thin fingers. He also had trouble in walking and sitting straight for a longer time.
- John Tavener: A british composer, John Tavener was known for his works like Song for Athene. He was diagnosed with Marfan syndrome in 1990, prior to which he had two heart attacks. At the age of 69, he died in 2013.
Though complex, it is essential to diagnose and manage Marfan syndrome. However, the outlook of patients suffering from Marfan syndrome has improved since 1970s. This inspires further endeavors for treating Marfan syndrome.