Marfan syndrome is an autosomal dominant disorder of the connective tissue. It was first described by the French pediatrician Antoine Marfan in 1896.
There are more than 25-30 different signs and symptoms in Marfan syndrome which can be of variable intensity and differ from patient to patient. Some people may not show any signs and symptoms. This condition worsens with age. Marfan syndrome becomes more obvious as changes occur in connective tissue.
The major systems affected are:
Skeletal system
The facial appearance of affected patients may be distinctive, with elongation and asymmetry. Sometimes there may be a high arched palate resulting in speech disorders [4]. Tall stature along with long thin digits and alteration in body proportions are seen. Wrists may be thin and weak. The arm span measured from the extended fingers often exceeds the height of the patient. Along with this the patient may show flat feet, hammer toes or stooped shoulders. There may be pain in joints, muscle and bones [5].
Eyes
Weakness of suspensory ligament of the eye may cause subluxation of lens, which is a common clinical feature in patients. Myopia and astigmatism may also be present.
Cardiovascular system
The most serious signs and symptoms of Marfan syndrome involve the cardiovascular system (CVS) which can lead to severe complications. Following degeneration in the media of the vessel wall, the aortic valve ring may dilate and produce an incompetent valve. Mitral valve is mainly involved resulting in mitral valve prolapse or regurgitation [6]. Typically, CVS symptoms present with fatigue, shortness of breath and tiredness. Heart murmur and angina pectoris may also be present. An aneurysm may occur in the ascending aorta leading to dissection or rupture.
Spinal affections
People with Marfan syndrome have a risk of developing scoliosis.
Skin
Striae distensae are very common and usually occur over shoulders and hips.
There is no objective diagnostic test of this condition. Since it affects multiple organ systems, a multidisciplinary approach is needed [7].
The diagnosis is done by a complete family history and a thorough examination of the patient’s eyes, heart and bone structure. The thumb sign and wrist sign are elicited for diagnosis.
An echocardiogram must be done to see the heart’s valves and aorta, a plain cardiogram is not sufficient. An echocardiogram will show images of heart in motion. A CT scan or MRI scan maybe done to visualise the heart.
An ophthalmologist will use a slit lamp examination to identify a dislocated lens along with other tests to check eye pressure and retina.
Genetic testing can be done by analysing the fibrillin gene-1 [8].
Marfan syndrome is incurable, but treatment is focussed at reducing pain and preventing complications. The life expectancy has increased over the period of years [9]. An individualized treatment will be selected depending on the severity of symptoms.
Regular echocardiograms should be done to evaluate the status of the aorta and heart valves. Occasionally, a CT scan and MRI scan maybe required. Medications mainly beta blockers maybe given to reduce heart rate and keep blood pressure in control.
An ophthalmologist should regularly check eyes for any vision problems. Most cases can be corrected by glasses or corrective surgery.
If musculoskeletal system is affected patient should check on regular basis for any joint pains, or any deformity should be corrected by orthopaedic surgery as these deformities can limit functioning of the patient.
Surgery in Marfan syndrome is done in cases of aortic rupture or aortic dissection. Valve repair or replacement surgery may also be necessary [10].
Regular moderate physical exercise is recommended.
The prognosis of the disease has vastly improved and life expectancy of patient has also increased. The most important factor is early diagnosis, so that patient can benefit from lifestyle modifications thus increasing the life expectancy. Good medical care and social support can help both adults and children with Marfan syndrome. Average life expectancy of people with Marfan syndrome is about 70 years [3].
Mutations in fibrillin gene (FBN1) [1] on chromosome 15 have been indicated to cause Marfan syndrome. Chromosome 15 encodes fibrillin gene which produces fibrillin, an important component of extracellular matrix as well as maintaining elastic fibres which provide strength and flexibility to the entire body.
Occasionally, mutations occur in Tumour growth factor-beta (TGF-β).
More than 500 fibrillin gene mutations have been identified out of which all are unique to the affected individual or family members. Different gene mutations are responsible for genetic heterogeneity.
As it is a genetic condition, the greatest risk factor for Marfan syndrome is having one parent with this condition [2].
Marfan syndrome affects 1 in every 3000-5000 people, affecting males and females equally. It appears to be distributed equally among all races and backgrounds.
It is one of the more common inheritable disorders. Since it is autosomal dominant, it means that any parent who has it has 50% risk of giving it to the child. 3 out of 4 cases are inherited, which is due to defects or disruptions of fibrillin-1 gene (FBN-1).
There is a 25% chance of spontaneous mutations known as sporadic cases where a patient who presents with Marfan syndrome has no family history of the disorder. Another characteristic feature of this syndrome is variable expression which means different members of a family affected with Marfan syndrome will show varied symptoms of different severity.
Marfan syndrome is caused by mutations in FBN1 gene present on chromosome 15, which encodes for fibrillin-1. Fibrillin is a type of glycoprotein which is an important component of extracellular matrix. This extracellular matrix is required for formation of connective tissue as well as maintaining it. Extracellular matrix is a storehouse of growth factors. Fibrillin helps in formation of microfibrils which give elasticity and strength to connective tissue.
Most mutations are unique and mainly affect a single amino acid of the protein. There is no particular spot for mutation to occur, the entire gene is affected. Severe cases of Marfan syndrome have been noted in the region encompassing exons 24 to 32.
Fibrillin mutations are seen in people who do not show Marfan syndrome but have related connective tissue disorder. Thus an abnormality in fibrillin gene leads to decreased production of microfibrils leading to resulting in connective tissue all throughout the body.
Transforming growth factor beta plays an important role in this condition, wherein fibrillin-1 binds to an inactive form of TGF-β resulting in fibrillin being unavailable for biological activity. The simplest theory states that the decrease in fibrillin along with increased levels of TGF-β is responsible for the pathology. TGF-β results in release of inflammatory proteases which gradually destroy elastic fibres and extracellular matrix. As elastic fibres are richly found in the aorta, ligaments and ciliary zonules of the eye, these areas are the worst affected.
Prevention is mainly for the complications which can occur. To prevent these early diagnoses helps to start treatment according to the patient’s severity of symptoms. Regular check-ups should be done especially of the eyes and heart. Spontaneous gene mutations cannot be prevented. Genetic counselling is recommended for couples with a history of this condition who wish to have children.
Marfan syndrome is a genetically inherited disorder that affects the human connective tissues. Since a major part of the body is made up of connective tissue, multiple organs are affected. Genetically, Marfan syndrome is autosomal dominant, where abnormality in the gene causes a myriad of clinical features mainly affecting the skeletal system-bones and muscle, cardiovascular system-heart and blood vessels and the ocular system.
Arachnodactyly which means spider like fingers in Greek is the hallmark of this condition due to the disproportionately long hands and fingers. Along with long and slender toes and fingers, there may be loose joints resulting in hypermobility. External manifestations are the main key in diagnosing this condition and even two patients from same family may look different. Intelligence is not affected.
Marfan syndrome is an inherited disorder that affects the connective tissue which is the material between cells. This connective tissue gives strength , flexibility and elasticity to the entire body. The condition affects many organs of the body, mainly the heart, eyes and skeleton.
The symptoms presented will vary from patient to patient. The severity increases with age. People with this syndrome tend to look unusually tall and thin. Patients show abnormally long fingers and toes. Most patients with Marfan syndrome may have a narrow face, along with curved spine or any other bony deformities. More than half of the patients will show blurring of vision for far away objects, or the lens may get dislocated from its normal position. Changes in heart and blood vessel may cause tiredness, shortness of breath. This is due to changes in the structure of the heart valves.
Genetic mutations are responsible for this syndrome due to which this condition has a high chance of being passed on to children.
Treatment mainly consists of relieving symptoms depending on the severity hence treatment plan will vary. The medical provider will take a complete history including family history and clinical examination to confirm this condition. Imaging techniques mainly echocardiogram to study the heart functioning are done. CT and MRI scans may also be suggested.
Marfan syndrome is incurable. The objective of the treatment is to prevent any complications and ensure that the patient can lead normal lives. Lifestyle modifications along with counselling help the patient.The most important aspect is early identification of this condition and treatment for prevention of complications.
Regular monitoring and modern treatment allows patients to lead a normal life span.