Course:MEDG550/Student Activities/Marfan Syndrome

From UBC Wiki

Marfan Syndrome (MFS) is a genetic condition that affects the connective tissue in many different parts of the body. Connective tissue is like the glue that holds the body together. It provides strength and flexibility to many structures, including bone, muscle, blood vessels, and heart valves [1]. MFS is caused by changes in a section of DNA called the FBN1 gene. The FBN1 gene contains instructions for making the protein fibrillin 1, a building block of connective tissue.

MFS affects people differently. Some people may experience very mild symptoms, while others may have severe, life-threatening symptoms. Generally, people with MFS tend to be tall and thin. They may have unusually flexible (hypermobile) joints and/or curving of the spine (scoliosis). The most serious concern for people with MFS is a weakened aorta, the blood vessel that carries blood from the heart to the rest of the body [2]. This can be life-threatening [2]. Most people with MFS can expect to have a normal lifespan, provided they receive the proper medical care [3].

Signs and Symptoms

Aortic dissection

There are many clinical features seen in people with MFS. Not all people show every sign, but most people will have a combination of cardiovascular (heart and blood vessel), eye, and skeletal symptoms. MFS symptoms vary widely in age of onset, severity, and rate of progression [1]. In more severe cases, features may be seen prenatally or at birth, while in mild cases, features may not be seen until old age [4]. This is not an exhaustive list, but highlights the more common findings in MFS.

Cardiovascular (heart and blood vessels)

  • Aortic root dilatation
    • The aorta is the blood vessel that carries blood from the heart out to the body.
    • The aorta is prone to expansion (dilation) at its base, where it connects to the heart (root). If dilation occurs, there is a risk that it will tear or rupture [5].
  • Aortic dissection
    • Tearing of the aortic wall, so blood enters between the inner and outer layers of the aortic wall.
  • Mitral valve prolapse (MVP)
    • The valve connecting the chambers in the left side of the heart (left atrium to the left ventricle) does not close properly. This can lead to backflow of blood (regurgitation) or more serious complications [5].

Eyes

Ectopia lentis
  • Near-sightedness (myopia)
    • The most common feature.
    • Typically occurs during childhood and progresses (worsens) quickly [3].
  • Displacement of the lens of the eye (ectopia lentis)
    • This is considered a hallmark feature of MFS, and it occurs in about 60% of affected individuals [3]
  • Glaucoma, early cataracts, and retinal detachment may also occur

Skeletal

Arachnodactyly

Other

  • Stretching of the dura membrane that surrounds the spinal cord (dural ectasia)
    • This can cause lower body pain or headaches [1]
  • Abnormal accumulation of air between the membranes that line the lungs (pneumothorax) [3]

Diagnosis

The average age of diagnosis is 19 years [4]. Diagnosing MFS is complex, and providers typically follow the revised Ghent criteria to find patients with MFS [4]. Usually, people with a family history of the condition must show signs like aortic root enlargement or ectopia lentis to be diagnosed, or they may have a pathogenic change in FBN1, or they may have a number of other symptoms that would suggest MFS [3] [4]. Individuals without a family history must be found to have a pathogenic change in FBN1, and either ectopia lentis or aortic root enlargement [3].

Management

Treatment

There is no cure for MFS, but with early treatment and management of symptoms, the risk for developing life-threatening concerns can be reduced. Because MFS affects people in different ways and with different severity, some people may require more treatment for their symptoms than others. Individuals with MFS require care from many health professionals to treat different symptoms. Ophthalmologists treat eye problems, such as cataracts or glaucomas, which may require surgery or eye drops[3]. Orthopedists treat bone problems, such as scoliosis, which can require bracing or surgery to prevent the curving of the spine from getting worse[1]. Cardiologists treat heart conditions and cardiothoracic surgeons perform surgery on organs in the chest[3]. Medication may be prescribed by doctors, such as beta blockers or angiotensin receptor blockers, which manage heart problems[1].  

Surveillance

Management of Marfan syndrome is a long-term process and includes many checkups for each condition. Individuals with MFS should get their length, weight, and height measured every time they visit their family doctor[3]. While bones are growing, they should be checked every time they visit their orthopedist to look for signs of scoliosis or chest problems[3]. They should also have their eyes and heart checked once a year[1].

Lifestyle Changes and Considerations

Managing MFS can also require lifestyle changes to prevent symptoms from getting worse. Anything that can excite the heart, such as decongestants (medicine for stuffy noses) or caffeine should be avoided[3]. It is also recommended that individuals with MFS avoid demanding physical activities and contact sports, such as football or basketball[1]. However, light exercise may be encouraged every once in a while and physical or occupational therapy can also help with muscle strengthening to help with muscle and bone problems[1]. LASIK eye surgery should also be avoided, as it can cause further eye problems[3].

Incidence

About 1 in 5,000 to 1 in 10,000 people have MFS. Men and women are affected equally, and it affects people of all ethnicities [3].

Genetics

MFS is caused by changes (or variants) in the gene FBN1. This gene encodes fibrillin 1, an important component of connective tissue in the body. Changes in FBN1 cause fibrillin to not work as it should, and as a result, lead to the signs we see in people with MFS.

Genetic Counselling

Inheritance

Autosomal Dominant Inheritance

MFS is passed down through families in what is called an autosomal dominant manner. This means that of the two copies of the FBN1 gene that we have (one copy from our mother and one copy from our father), only one copy needs to have a change to cause MFS. Therefore, a person with MFS has one working copy of FBN1 and one changed copy. If that person goes on to have children, they can only pass one copy of FBN1 onto their child, and there is a 50:50 chance whether they will pass on the working copy or the changed copy. If they pass on the changed copy of FBN1, that child will also have MFS. Because MFS is such a variable condition, it is very difficult to predict what the condition will look like for a child who has inherited MFS.

Approximately 75% of people with MFS have a family history of the condition, while for the remaining 25% of people, the genetic change is new in them (also called de novo) [3].

Genetic Testing

If a person is suspected of having MFS, or if they have been diagnosed with MFS clinically, genetic testing may be offered to confirm or rule out a diagnosis. Genetic testing may be particularly helpful in diagnosing individuals who are mildly affected and/or for identifying other affected family members.

Before pursuing genetic testing, it is important to meet with a genetic counsellor or other genetics health care professional. To find one near you, go to Find a Clinic (Canada) or Find a Genetic Counselor (USA).

MFS and Pregnancy

Women with MFS who are pregnant need to be monitored closely throughout the pregnancy and in the period immediately after giving birth, due to an increased risk of aortic dissection [3] [6]. Women should have an echocardiogram (an ultrasound of the heart) every 2-3 months while pregnant to monitor the size of their aortic root.

Women who have an aortic root diameter >45mm should avoid pregnancy, or it is recommended that they have prophylactic aortic root repair before getting pregnant [7] [5]. In women who have already had an aortic dissection, pregnancy is discouraged [8].

Couples may consider preimplantation genetic diagnosis (PGD) if they want to ensure they do not pass on MFS. If the woman is affected, couples may also wish to consider surrogacy, adoption, or childlessness [8]. Prenatal diagnosis is also an option, but only in the scenario in which a genetic diagnosis has already been found in the family. In such a case, chorionic villus sampling (CVS) could be done between 11 and 14 weeks gestation, or amniocentesis could be done after 15 weeks [6]. These are invasive procedures that have their own risks and benefits, but would allow for prenatal identification of MFS in the fetus. A genetic counsellor can help a family decide what is best for them.

Living with MFS

People who live with MFS can lead fulfilling lives. A Hungarian study found that people with MFS reported greater life satisfaction and happiness than the general Hungarian population [9]. However, life with MFS comes with a unique set of challenges. It is important to remember that every person experiences MFS differently, so they may or may not relate to the descriptions below. The experience can depend on how severe symptoms are, access to social and medical supports, and personal outlook on living with a chronic disease.

Self-esteem

Some people with MFS report lower self-esteem due to the physical features and exercise restrictions that come with the condition. This is especially important for teenagers, but adults can also be impacted. MFS comes with a set of physical features such as being tall and thin, having long fingers, and sometimes stretch marks. Some people believe that the way they look makes it more difficult to date and fit in with peers. Not being able to participate in sports and physical activity can also limit their social circles.[10]

Chronic pain and fatigue

People with MFS report that chronic pain and fatigue can affect their quality of life. If not properly managed, pain and fatigue can interfere with school and work, and reduce general life satisfaction.[10]

Quality of Life

Research on quality of life for people living with MFS shows mixed results. Some studies found that people living with MFS have greater life satisfaction than the general population, while other studies found they have less life satisfaction. Quality of life can be lowered by depression, anxiety, fatigue, pain, low self-esteem, and having more severe physical symptoms.[10] Developing positive coping strategies can improve quality of life. A pilot study found that an MFS group rehabilitation program improved physical and mental health.[11] Participants participated in personalized exercise regimes, group therapy, and individual counselling for employment and dietary concerns.[11] See the Patient Resources section below to find supports near you. You can also ask your physician or genetic counsellor.

Patient Resources

See a list of virtual support groups for MFS and related conditions (click here).

You can also find information about the medical, genetic, and daily life aspects of living with MFS.

See a list of Canadian clinics that specialize in aortic disorders (click here).

You can ask a question to the Medical Advisory Board by phone or email (click here).

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Genetics Home Reference, 2018 https://ghr.nlm.nih.gov/condition/marfan-syndrome#
  2. 2.0 2.1 2.2 Dean, J. (2007). Marfan Syndrome: Clinical Diagnosis and Management. Eur J Hum Genet. 15: 724-733
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 GeneReviews, 2017 https://www.ncbi.nlm.nih.gov/books/NBK1335/
  4. 4.0 4.1 4.2 4.3 Groth, K.A. et al. (2015). Prevalence, incidence, and age at diagnosis of Marfan Syndrome. Orphanet J Rare Dis. 10:153. doi 10.1186/s13023-015-0369-8
  5. 5.0 5.1 5.2 Pepe, G. et al. (2016). Marfan Syndrome: Current Perspectives. Appl Clin Genet. 9: 55-65
  6. 6.0 6.1 Grigoriu, A.C. et al. (2010). Marfan Syndrome and Pregnancy: Clinical Implications and Management. Fet Mat Med Rev. 21(3): 225-241
  7. Smith, K. and B. Gros. (2016). Pregnancy-related acute aortic dissection in Marfan Syndrome: A review of the literature. Congenit Heart Dis. 12(3): 251-260
  8. 8.0 8.1 Mulder, B.J.M. and L.J. Meijboom. (2012). Pregnancy and Marfan Syndrome. J Am Coll Cardiol. 60(3): 230-231
  9. Pólos, M. et al. (2020). Psychological factors affecting Marfan syndrome patients with or without cardiac surgery. Ann Palliat Med. 9(5):3007-3017. doi 10.21037/apm-20-546
  10. 10.0 10.1 10.2 Nielsen C. et al. (2019). A Review of Psychosocial Factors of Marfan Syndrome: Adolescents, Adults, Families, and Providers. J Pediatr Genet. 8(3):109-122. doi: 10.1055/s-0039-1693663
  11. 11.0 11.1 Benninghoven, D. et al. (2017). Inpatient rehabilitation for adult patients with Marfan syndrome: an observational pilot study. Orphanet J Rare Dis. 12:127. doi: 10.1186/s13023-017-0679-0

See Also