What is Marfan syndrome and what causes it?
Marfan syndrome is a rare genetic disorder of the connective tissue, affecting the skeleton, lungs, eyes, heart and blood vessels. The condition is caused by a defect in the gene that tells the body how to make fibrillin-1, often from a parent who is also affected. One quarter of cases may be the result of a spontaneous gene mutation.
What are the chances of inheriting Marfan syndrome?
Each child of an affected parent has a 50-50 chance of inheriting the defective gene. In about 25 percent of the people who have Marfan syndrome, the abnormal gene doesn't come from either parent. In these cases, a new mutation develops spontaneously. Marfan syndrome affects men and women equally and occurs among all races and ethnic groups.
Which genetic tests are used to diagnose Marfan syndrome?
The FBN1 gene is the gene associated with the true Marfan syndrome. Genetic testing of the FBN1 gene identifies 70 - 93 percent of the mutations and is available in clinical laboratories.
Why do people with Marfan syndrome have crowded teeth?
Often, people with Marfan syndrome have a long, narrow face and the roof of the mouth may be higher than normal, causing the teeth to be crowded. Marfan syndrome causes many changes to occur within the body structures, including dental and skeletal (bone) problems.
How does someone get Marfan syndrome?
Marfan syndrome is caused by a mutation in a gene called FBN1. The mutation limits the body's ability to make proteins needed to build connective tissue. One in four people with Marfan syndrome develops the condition for unknown reasons. A person with Marfan syndrome has a 1 in 2 chance of passing it on to their child.
Can you pass on Marfan syndrome?
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.
Can you get Marfan syndrome if your parents don't have it?
Most kids with Marfan syndrome have it because they inherited the abnormal gene from one of their parents, but sometimes it happens in a child without a family history.
Is Marfan syndrome inherited or acquired?
It is caused by genetic changes in the FBN1 gene, which provides instructions for making a protein called fibrillin-1. Marfan syndrome is inherited in an autosomal dominant pattern.
Can marfans skip a generation?
Approximately 25 percent of individuals who have Marfan syndrome, have the condition as a result of a new (de novo) mutation. When a parent has Marfan syndrome, each of his or her children has a 50 percent chance (1 chance in 2) to inherit the FBN1 gene.
At what age is Marfan syndrome usually diagnosed?
Study Patients. Their ages when the Marfan syndrome was first diagnosed ranged from 32 to 72 years (mean age, 46 years). Of these 28 patients, 7 were older than 50 years of age at the time of initial diagnosis.
Should you have children if you have marfans?
If you have Marfan syndrome and are considering pregnancy, it is very important to talk to your doctor. The condition and treatments increase the chance of problems for both you and your unborn baby. Pregnancy creates extra stress on the heart and blood vessels.
Is Marfan syndrome painful?
Skeletal problems that develop as a result of Marfan syndrome can sometimes cause significant pain and discomfort. They may also affect your appearance, which some people find affects their confidence and self-esteem.
What is the average lifespan of someone with Marfan syndrome?
The prevalence of the syndrome is 7-17/100,000. The mean life expectancy for untreated patients with Marfan syndrome is 32 years with aortic dissection, aortic rupture or cardiac failure due to mitral and aortic valve regurgitation as the predominant cause of death in > 90% of the cases.
Is Marfan syndrome detected before or after birth?
Prenatal testing for Marfan syndrome can be carried out approximately 10 to 12 weeks into the pregnancy using chorionic villus sampling (CVS). CVS involves taking a small sample of cells from the organ that links the mother's blood supply with her unborn baby's (the placenta) through the entrance of the womb.
How long does someone with Marfan syndrome live?
Despite the high risk for Marfan related cardiovascular problems, the average life expectancy of those with Marfan syndrome is nearly 70 years. The life expectancy in this syndrome has increased to greater than 25% since 1972.
What is the average lifespan of someone with Marfan syndrome?
The prevalence of the syndrome is 7-17/100,000. The mean life expectancy for untreated patients with Marfan syndrome is 32 years with aortic dissection, aortic rupture or cardiac failure due to mitral and aortic valve regurgitation as the predominant cause of death in > 90% of the cases.
How is the family of a person with Marfan syndrome affected?
The abnormal gene happens as follows: In about 3 out of 4 cases, the gene is inherited from a parent who is affected. Each child of an affected parent has a 1 in 2 chance of having the disorder (autosomal dominant inheritance). In about 1 out of 4 cases, the abnormal gene is from a new mutation.
What is the average height of someone with Marfan syndrome?
Mean length at birth was 53 +/- 4.4 cm for males and 52.5 +/- 3.5 cm for females. Mean final height was 191.3 +/- 9 cm for males and 175.4 +/- 8.2 cm for females.
What is the greatest risk factor for Marfan syndrome?
Risk factors. 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.
Why does my aorta bulge out?
The pressure of blood leaving your heart can cause the wall of your aorta to bulge out , like a weak spot in a tire. In people who have Marfan syndrome, this is most likely to happen at the aortic root — where the artery leaves your heart.
What is the effect of Marfan syndrome on the aorta?
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.
What are the complications of Marfan syndrome?
The most dangerous complications of Marfan syndrome involve the heart and blood vessels. Faulty connective tissue can weaken the aorta — the large artery that arises from the heart and supplies blood to the body.
How do people with Marfan syndrome get their genes?
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.
What causes the wall of the aorta to bulge out?
Aortic aneurysm. The pressure of blood leaving your heart can cause the wall of your aorta to bulge out, like a weak spot in a tire. In people who have Marfan syndrome, this is most likely to happen at the aortic root — where the artery leaves your heart. Aortic dissection. The wall of the aorta is made up of layers.
What is Marfan syndrome?
Overview. 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, ...
What causes aortic valve to leak?
Aortic root dilation: The aortic root is the area where the aorta meets the aortic valve. With Marfan syndrome, the aortic root may dilate or widen. This can cause the aortic valve to become stretched and leak. Arrhythmia (abnormal heart rhythm): May occur in some patients with Marfan syndrome.
How big is the aorta for surgery?
When the aorta diameter is more than 4.7 cm (centimeters) to 5.0 cm (depending on your height), 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.
What happens to the blood vessels in Marfan syndrome?
Blood vessel changes: With Marfan syndrome, the walls of the blood vessels become weak and dilate (stretch). These blood vessel changes often affect the aorta, the major artery that carries blood from the heart to the rest of the body.
What is the condition called when the connective tissue is damaged?
Marfan syndrome (also called Marfan’s syndrome or Marfans 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 isn’t normal. As a result, many body systems are affected, including the heart, blood vessels, bones, tendons, cartilage, eyes, nervous system, skin and lungs.
How does Marfan syndrome work?
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.
What percentage of Marfan syndrome is genetic?
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.
Why do people with Marfan syndrome have a narrow face?
Often, people with Marfan syndrome have a long, narrow face and the roof of the mouth may be higher than normal, causing the teeth to be crowded. Marfan syndrome causes many changes to occur within the body structures, including dental and skeletal (bone) problems.
How is Marfan Syndrome Managed?
People with Marfan syndrome are born with it, but features of the condition are not always present right away. Some people have a lot of Marfan features at birth or as young children – including serious conditions like aortic enlargement. Others have fewer features when they are young and don’t develop aortic enlargement or other signs of Marfan syndrome until they are adults. Some features of Marfan syndrome, like those affecting the heart and blood vessels, bones or joints, can get worse over time.
How does Marfan affect the body?
Marfan syndrome and related conditions affect the body’s connective tissue. Connective tissue holds the body together and plays a role in its growth and development. Because connective tissue is found throughout the body, Marfan syndrome and related disorders can affect many parts of the body, including the heart and blood vessels, bones and joints, eyes, skin, and lungs.
What is Marfan syndrome?
Marfan syndrome is a genetic condition that affects the body’s connective tissue. Connective tissue holds all the body’s cells, organs and tissue together. It also plays an important role in helping the body grow and develop properly.
What is it called when the aorta is enlarged and the valves cannot come together?
Aortic regurgitation is when the aortic valve does not fully close and blood leaks back into the heart. This often happens when the aorta is enlarged and the valves cannot fully come together. The only symptoms a person may have are forceful heartbeats and shortness of breath during light activity.
How many people have Marfan syndrome?
About 1 in 5,000 people have Marfan syndrome, including men and women of all races and ethnic groups. About 3 out of 4 people with Marfan syndrome inherit it, meaning they get the genetic mutation from a parent who has it. But some people with Marfan syndrome are the first in their family to have it; when this happens it is called a spontaneous mutation. There is a 50 percent chance that a person with Marfan syndrome will pass along the genetic mutation each time they have a child.
What is it called when you tear your aortic wall?
A tear or rupture between layers of the aortic wall is called an aortic dissection. When this happens, people experience severe pain in the center of their chest, stomach, or back. They may describe the pain as “sharp,” “tearing” or “ripping.” The location of the pain may change. Sometimes, the pain is less severe, but people still have the feeling that “something is very wrong.” If a dissection is suspected, a person needs immediate medical attention and should go to a hospital emergency department right away.
What is the mitral valve?
Mitral valve prolapsed is a condition in which the flaps of one of the heart’s valves (the mitral valve, which regulates blood flow on the left side of the heart) are “floppy” and don’t close tightly. Symptoms can include irregular or rapid heartbeats and shortness of breath. Some people also have leaking of the mitral valve. A small amount of leaking is usually not a problem, but a person may need surgery if the mitral valve leaks a lot.
What is Marfan syndrome?
Marfan syndrome is one of the most common inherited disorders of connective tissue. It is an autosomal dominant condition occurring once in every 10,000 to 20,000 individuals. There is a wide variability in clinical symptoms in Marfan syndrome with the most notable occurring in eye, skeleton, connective tissue and cardiovascular systems.
What is the treatment for Marfan syndrome?
Individuals who have Marfan syndrome are treated by a multidisciplinary medical team that includes a geneticist, cardiologist, ophthalmologist, orthopedist and cardiothoracic surgeon.
Is Marfan syndrome inherited?
Approximately 25 percent of individuals who have Marfan syndrome, have the condition as a result of a new (de novo) mutation. When a parent has Marfan syndrome, each of his or her children has a 50 percent chance (1 chance in 2) to inherit the FBN1 gene. While Marfan syndrome is not always inheri ted, it is always heritable.
What is the chance of a child with Marfan syndrome being born to a parent who does not show features of?
When a child with Marfan syndrome is born to parents who do not show features of the Marfan syndrome, it is likely the child has a new mutation. In this family situation, the chance for future siblings (brothers and sisters of the child with Marfan syndrome) to be born with Marfan syndrome is less than 50 percent.
What is the FBN1 gene?
The FBN1 gene is the gene associated with the true Marfan syndrome. Genetic testing of the FBN1 gene identifies 70 - 93 percent of the mutations and is available in clinical laboratories. However patients negative for the test for gene mutation should be considered for evaluation for other conditions that have similar features of Marfan syndrome such as Dietz syndrome, Ehlers Danlos syndrome, and homocystinura. To unequivocally establish the diagnosis in the absence of a family history requires a major manifestation from two systems and involvement of a third system. If a mutation known to cause Marfan syndrome is identified, the diagnosis requires one major criterion and involvement of a second organ system.
What is FBN1 mutation?
FBN1 mutations are associated with a broad continuum of physical features ranging from isolated features of Marfan syndrome to a severe and rapidly progressive form in newborns. What is Marfan syndrome? Marfan syndrome is one of the most common inherited disorders of connective tissue.
What are the most life threatening symtoms of Marfan syndrome?
Cardiovascular malformations are the most life threatening symptom of Marfan syndrome. They include dilated aorta just as it leaves the heart (at the level of the sinuses of Valsalva), mitral valve prolapse, tricuspid valve prolapse, enlargement of the proximal pulmonary artery, and a high risk for aortic tear and rupture (aortic dissection).
What is Marfan syndrome?
Marfan syndrome is a rare genetic disorder of the connective tissue, affecting the skeleton, lungs, eyes, heart and blood vessels . The condition is caused by a defect in the gene that tells the body how to make fibrillin-1, often from a parent who is also affected. One quarter of cases may be the result of a spontaneous gene mutation.
What medical problems are associated with Marfan syndrome?
Marfan syndrome primarily affects the cardiovascular and skeletal systems. People with the condition may also have vision problems ; many are near-sighted, and about 50 percent suffer from dislocation of the ocular lens.
How is Marfan syndrome diagnosed?
People with Marfan syndrome exhibit different combinations of symptoms. Because symptoms of the condition overlap with other related connective tissue disorders, it is vitally important that your physicians be knowledgeable about Marfan syndrome. Tests include:
What doctor monitors Marfan syndrome?
The advances in medical and surgical management of children and adults with Marfan syndrome have resulted in high- quality, productive and long lives. A cardiologist will monitor the aorta and heart valves, an ophthalmologist will monitor the lens and retina of the eyes and an orthopaedist will monitor the spine, legs and feet.
How does Marfan affect the heart?
Marfan syndrome affects the cardiovascular system by making the aorta (an artery that begins at the heart and is the largest in the human body) wider and more fragile. This can lead to leakage of the aortic valve or tears ( dissection) in the aortic wall, which may require surgery to repair. Additionally, the heart’s mitral valve may leak and an irregular heart rhythm may develop.
What is the genetic mutation of FBN1?
Genetic test for a mutation in FBN1, the fibrillin-1 gene. Fibrillin is a component of microfibrils, a group of proteins that add strength and elasticity to connective tissue. A genetic mutation is found in 90 percent to 95 percent of people with Marfan syndrome.
What is the condition that makes your arms and legs flat?
Finally, Marfan syndrome may lead to curvature of the spine, an abnormally shaped chest that sinks in or sticks out, long arms, legs and fingers, flexible joints and flat feet. Because of this, people with the condition are typically taller and thinner in stature.
What are the characteristics of Marfan syndrome?
Other common features of Marfan syndrome include: Unusually flexible joints. Long and narrow face. Highly arched roof of the mouth. Crowded teeth. Scoliosis.
How many chances do you have of inheriting Marfan syndrome?
Each child of an individual with Marfan syndrome has a 50% chance of inheriting the mutation and the disorder. Offspring who inherit the mutation will have Marfan syndrome, although they could be more or less severely affected than their parent. [5]
What is Marfan syndrome?
Listen. Marfan syndrome is a disorder of the connective tissue. Connective tissue provides strength and flexibility to structures throughout the body such as bones, ligaments, muscles, walls of blood vessels, and heart valves. Marfan syndrome affects most organs and tissues, especially the skeleton, lungs, eyes, heart, ...
How many copies of Marfan syndrome are there?
Marfan syndrome is inherited in an autosomal dominant manner. All individuals inherit two copies of each gene. In autosomal dominant conditions, an individual has a disease-causing mutation in only one copy of the gene that causes the person to have the disease.
What is the HPO database?
People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources.
What causes shortness of breath and fatigue?
Most people with Marfan syndrome have abnormalities of the heart and the aorta. Leaks in valves that control blood flow through the heart can cause shortness of breath, fatigue, and an irregular heartbeat felt as skipped or extra beats (palpitations). If leakage occurs, it usually affects the mitral valve, which is a valve between two chambers ...
What is Project OrphanAnesthesia?
Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.
What is Marfan syndrome?
One of the most common inherited disorders affecting connective tissue, Marfan syndrome (MFS) is an autosomal dominant condition with a reported incidence of 1 in 3000 to 5000 individuals. [1] [2] There is a broad range of clinical severity associated with MFS, ranging from isolated features of MFS to neonatal presentation of severe and rapidly progressive disease involving multiple organ systems. [3] The syndrome is associated with classic ocular, cardiovascular, and musculoskeletal abnormalities, although involvement of the lung, skin and central nervous system may also occur. Decreased life expectancy occurs primarily due to aortic complications. Outcome improves with early diagnosis, medical treatment to delay or prevent the progression of aortic dilatation, and timely elective surgery.
What is the diagnosis of Marfan syndrome?
The basis of a diagnosis of Marfan syndrome (MFS) is upon the presence of characteristic manifestations, particularly aortic root dilatation/dissection and ectopia lentis, skeletal findings, mitral valve prolapse, dural ectasia, pneumothorax, and skin striae.
What is the primary cause of morbidity and mortality in Marfan syndrome?
Of primary concern is cardiac pathology. Aortic root disease, leading to aortic regurgitation, aneurysmal dilatation, and dissection, is the primary cause of morbidity and mortality in MFS, in up to 60% to 80% of patients.
How long does Marfan syndrome last?
The lifespan of untreated patients with the classic Marfan syndrome (MFS) was approximately 32 years in 1972 but has markedly increased to 72 years in 1993. [69] [70] Beta-blockers, noninvasive aortic imaging, and elective aortic root repair have all contributed to an improvement in survival. Life expectancy is significantly lower in men than in women.
What causes aortic dilation in Marfan syndrome?
The pathophysiology of aortic dilatation in Marfan syndrome (MFS) is a complicated process. Fibrillin-1 is a regulator of TGF-beta bioavailability, which in turn leads to inflammation, fibrosis, and activation of specific matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9. [10] Cystic medial degeneration of the aorta occurs when an accumulation of mucopolysaccharide cysts lead to the loss of vascular smooth muscle cells. Aortic wall weakening is due to increased release of MMP, cytokines, chemokines, prostaglandin derivatives, and elastic degradation fragments. These factors, in conjunction with decreased collagen, reduce aortic structural integrity and lead to aneurysmal dilatation. [11] Reduced or altered forms of fibrillin-1 can stimulate the release of sequestered TGF-beta and increase its activity. [12] MFS is therefore caused by vascular remodeling due to a combination of structural microfibril changes, excess TGF-beta, and overexpression of MMP-2 and MMP-9. [11] The role of TGF-beta in the pathophysiology of MFS has been solidified by the use of the therapeutic angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs), both proven to decrease TGF-beta activity. Early studies in a mouse model of MFS have shown the utility of a TGF-beta-neutralizing antibody or the ARB losartan in the treatment of the disease. [13] Comparatively, mutant mice treated with propranolol only exhibited a moderate reduction in the rate of aortic root dilation. Human studies substantiated that ARB therapy resulted in a significant reduction in the rate of change in the aortic root diameter as compared with beta-blocker therapy alone. [14] Various conditions with pronounced clinical overlap with MFS are caused by primary mutations in genes encoding direct effectors and/or regulators of TGF-beta signaling, including Loeys-Dietz syndrome (LDS) and Shprintzen-Goldberg syndrome (SGS).
How many people are affected by MFS?
Approximately 1 in every 3000 to 5000 individuals is affected. The disease occurs worldwide, with no preference for race or gender. It exhibits complete penetrance with variable expression. [9] Twenty-five percent of cases present sporadically due to de novo mutations. [2] MFS is one of the most common single-gene malformation syndrome.
Is Marfan syndrome autosomal dominant?
Although Marfan syndrome (MFS) has an autosomal dominant inheritance, rare case reports have described recessive fibrillin 1 gene (FBN1) mutations. [4] While most individuals with MFS have an affected parent, 25% of patients develop the disease as a result of a de novo mutation involving the gene (FBN1) encoding the connective tissue protein fibrillin-1. [5] [6] FBN1 is a large gene (65 exons) located at chromosome 15q-21.1. Fibrillin-1 is a matrix glycoprotein that is the main constituent of elastic fibers. [7] [8] In less than 10% of patients with typical Marfan phenotype, no mutation in FBN1 is identifiable, likely due to complete allele deletion or altered regulation of the FBN1 gene. In patients with atypical presentations reminiscent of MFS, a mutation in a gene encoding for transforming growth factor-beta receptor (TGFBR) may be the cause. Some individuals with TGFBR1 or TGFBR2 mutations have clinical features consistent with MFS, while others have features of one of two other syndromes: Loeys-Dietz syndrome (LDS) or familial thoracic aortic aneurysm (FTAA) syndrome. [3]
Inheritance
Marfan syndrome is inherited in an autosomal dominant manner. Marfan syndrome is caused by the presence of one genetic change (called a mutation) in the FBN1 gene. We all have two copies of the FBN1 gene, one from mom and one from dad.
More Inheritance Content
Is there variable expression or incomplete penetrance of Marfan syndrome?
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