So Why Should We Care?

You may not have Marfan Syndrome. So why learn about it? 

Educating others about genetic disorders allows us all to be more aware of all the different types of people around us, and to not be so insensitive at times. While it's already hard enough to have to deal with the medical issues that Marfan Syndrome brings along, the last thing someone afflicted with the disorder needs is to feel like an outsider from comments and teasing. Simply knowing about disorders such as Marfan Syndrome will stop us from thinking, "What's wrong with that person?" to understanding that they're really just like everyone else... only maybe a bit taller and skinnier. 


Simply check out this article about Michelle Smith, now 22 years old, from Scarborough, Texas. Previously a cheerleader and gymnast, she had to give up sports and start having her health monitored after being diagnosed with Marfan Syndrome. But she then turned to new hobbies, such as pageantry and volunteer work, particularly to spreading awareness for the syndrome. The National Marfan Foundation honored her with a Silver Service award, and she even had the opportunity to meet several celebrities.

Michelle Smith, a beautiful young lady with Marfan Syndrome

Or ever heard of the popular indie rock band Deerhunter? If you haven't, listen to their song Helicopters. It's great:

The lead singer of the five-piece band is Bradford Cox, and he actually has Marfan Syndrome.

Deerhunter, with Bradford Cox on the far right

Cox preforming at Osheaga 2012

Constantly under judgement from audiences because of his 6-foot-4 and very, very skinny body, Cox admits that "it affects your personality, because a lot of your personality is a product of your self-image." People constantly spew insulting words like "hideous", "ugly", and "freak" in his direction, and some even mistake him for being anorexic. However, Cox manages to view his disorder as a strength, and as a performer, his "weird" appearance only adds to his "weird" but wonderful music. 


While these are just a couple examples of amazing people with Marfan Syndrome, more awareness from the public about Marfan Syndrome will support the many others who have it, and also prevent ignorance. At one point, people even thought that the Olympic swimming champion Michael Phelps had Marfan Syndrome, simply because he was lean and had long arms (here is an article from Fox News that goes further in-depth on the topic.) But anybody who was well-educated on the disorder would know that Marfan Syndrome would prevent Phelps from participating in any swimming activity, because of the dangerous impact it would have on his heart. 

Instead of confusing accusations of Marfan Syndrome, people should be able to focus on the actual issue on hand and play a role in aiding medical research so that better treatment can be provided for the individuals that do have the disorder. Check out the Marfan Foundation and the Marfan Trust for possibilities for donations and fundraising. Getting invoved will allow for results that increase early diagnosis, ensure life-saving treatment, and give relentless support to families, caregivers, and healthcare providers.

The Genetics

Genetic disorders occur as the result of defective genes that are passed on to the baby from the mother, the father, or both. Marfan Syndrome is an autosomal dominant disease. Autosomal means the mutation is in a gene located on one of the 22 pairs of autosomes, which are the numbered chromosomes that are the same in all males and females, since the 23rd pair are the sex chromosomes. Dominant refers to a gene that is always expressed, even if only one copy is present. When a parent with Marfan Syndrome passes on a mutated copy of the gene to his/her child, the child will inherit the disorder. However, a parent with the syndrome is also capable of passing on a normal (unchanged) copy of the gene. If a child inherits this normal gene, then he/she will not have the disorder.

Below is an example of a punnett square with one homozygous dominant parent with Marfan Syndrome (RR), and one parent who does not have Marfan Syndrome at all (rr). Since every possible outcome is homozygous (Rr), their child will definitely inherit the disorder, because the syndrome is dominant and therefore carried by the capital R. This means that one capital R is all that is needed for the syndrome to be expressed.

Below is different example of a punnett square with one heterozygous parent (Rr) with Marfan Syndrome, and one parent who does not have Marfan Syndrome at all (rr). Their child will have the disorder if they happen to be Rr, but will not have the disorder if they turn out to be rr, so it is a 50-50 chance.

If both parents have the disorder, then their children are guaranteed to have it as well. However, it is also possible for an individual to develop Marfan Syndrome even if neither parents have it at all. This is caused by a spontaneous gene mutation that happens in either the egg or sperm at the time of conception. Unaffected parents only have about a 1 in 10,000 chance of having a child with the syndrome.

As described in this article, scientists were able to discover the gene that caused Marfan Syndrome in 1991. Further studies allowed the exact position to be pinpointed. The FBN1 gene is located on the long arm (q) of chromosome 15 at position 21.1, from base pair 48,408,305 to base pair 48,645,787. 

The FBN1 gene (Source)

This gene encodes a large protein called fibrillin-1, which is a major building block of microfibrils. Microfibrils are structural components of the supporting matrices of the tissue of the eyes, aorta, lung airways, and the dura of the spinal column. Mutations in FBN1 reduce the amount of fibrillin-1 produced by the cell, alter the structure or stability of fibrillin-1, and/or impair the transport of fibrillin-1 out of the cell. This resuts in a severe reduction in the amount of fibrillin-1 available to form microfibrils. Without enough microfibrils, the overgrowth and instability of connective tissues in many parts of the body cause the signs and symptoms of Marfan syndrome to occur.

Interview with a Professional on Marfan Syndrome

While browsing on the internet for more information, I came across a page of the Cincinnati Children's Hospital Medical Center's website. They're currently ranked the third best children's hospital in the nation, three years in a row. Here is a link to the exact page, which is trying to reach out to children, adolescents, and young adults who have Marfan Syndrome to see if they are interested in participating in a medication study that compares the effect of beta blocker therapy to receptor blocker therapy on the rates of aortic growth and other cardiovascular outcomes.

Although I personally do not have Marfan Syndrome and am not interested or eligible to participate in the medical study, I continued to read through the page and came to a contact at the bottom. I felt that I could gain more information by speaking to an actual professional on my topic, so I decided to contact the name given via email. 

I conducted the email interview with Michelle S. Hamstra, M.S. (Master of Science), who works in the Department of Cardiology at Cincinnati Children's. After introducing myself and my purpose for contacting her, I asked her:

• What are the effects on the heart due to Marfan Syndrome?

• When are people usually diagnosed?

• What kind of medications are used to treat the syndrome?

• What effect do these medications have, and how effective are they in treating the syndrome?

She replied a couple days later with a ton of helpful information:

Good morning, Amanda.
Thank you for your email. 

Marfan syndrome is a genetic disorder that affects the body’s connective tissue. Connective tissue holds all the body’s cells, organs and tissue together. Because connective tissue is found throughout the body, Marfan syndrome can affect many different parts of the body. Features of the disorder are most often found in the heart, blood vessels, bones, joints and eyes. One effect Marfan syndrome can have on the heart is aortic enlargement (the main blood vessel that carries blood away from the heart to the rest of the body. It can become larger than it should and risks tearing or rupturing). Aortic enlargement can be life threatening. The lungs, skin and nervous system may also be affected.

About 3 out of 4 people with Marfan syndrome inherit it, meaning they get the genetic mutation from a parent who has it. A parent has a 50% chance of passing along the genetic mutation each time she/he has a child. If a parent is aware that she/he has Marfan syndrome, then the children are usually diagnosed early in childhood. But some people with Marfan syndrome are the first in their family to have it; when this happens it is called a spontaneous mutation.

Although people with Marfan syndrome are born with it, the features of the disorder are not always present right away. Some people have a lot of Marfan features at birth or as young children. Others have fewer features when they are young and don’t develop aortic enlargement or other signs of Marfan syndrome until they are older. Some features of the disorder can get worse over time.

While Marfan syndrome is a condition that cannot be cured, people can live long, full lives with proper treatment and management. Everyone is different, depending on how severe or mild their features are. Management includes limitations on physical activity, regular doctor appointments and other evaluations to monitor features/symptoms of the disorder. Treatment may include daily medications such as beta blockers (like atenolol/Tenormin) or angiotensin receptor blockers (like losartan/Cozar). These medications manage blood pressure and reduce stress that is placed on the heart. The goal of medical treatment is to control or slow the rate of growth (or dilation) of the aorta. Atenolol and Losartan’s effectiveness in controlling the rate of growth of the aorta is what we are currently researching. Clinical experience would suggest that when used properly, medication can help slow and control aortic enlargement for many people affected by Marfan syndrome. The study you read about that led you to email me, is ending this month. We hope to have results to share before the end of the year.

She even provided me with a very helpful website dedicated entirely to Marfan Syndrome in case I was further interested and needed more information: http://www.marfan.org/

I strongly encourage anyone interested as well to check out the website, and perhaps anyone with Marfan Syndrome to consider the medical study. 

What Marfan Syndrome Looks Like

You may not always be able to tell when someone has Marfan Syndrome, since with modern medicine and technology, many lead completely normal lives. The disorder only expresses itself with the physical deformities it carries, and does not affect the intelligence and thinking of the individual whatsoever. So what exactly does Marfan Syndrome look like?

Generally, people with Marfan Syndrome will have similar physical characteristics. As stated in my previous post, observable traits include a very tall, thin physique, with disproportionately long and flexible limbs, fingers, and toes. Usually, their arm span will be longer than their height. A narrow chest with either a caved in or protruding deformity, flat feet, a high arched palate (dental), and spinal curve may all be present, though it varies greatly.

Here are some examples of minor cases of Marfan Syndrome, with less recognizable characteristics. These individuals may seem more like they're just a little on the skinny side, and less like the carriers of a genetic disorder.

The long and thin fingers of a 13-year-old patient with Marfan Syndrome (Source)

The Steinberg sign and Walker-Murdoch sign, two hand signs used to evaluate joint mobility in Marfan patients (Source)

A 13-year-old boy with Marfan Syndrome (Source)

To demonstrate the wide range of the symptoms, here are some cases of severe Marfan Syndrome.

(Source)

 

 

 

 

An adolescent with Marfan Syndrome (Source)

Unaffected hands compared to the hands in Marfan Syndrome (Source)

Scoliosis associated with Marfan Syndrome (Source)

High arched palate in a Marfan's patient (Source)

Dislocated lens in Marfan's patient (Source)

Also, check out this video (Source) of an interview with a lovely woman who has Marfan Syndrome explaining and demonstrating her physical symptoms:

An Introduction to Marfan Syndrome

When I first started out on the research project, I had no idea what Marfan Syndrome was. I had never even heard of it. So of course, I needed to educate myself before I could educate others. Naturally, I set out to find the essentials of the disorder first. Here, I have compiled a general introduction to Marfan Syndrome:


Marfan Syndrome was first described in 1896 by French physician Antoine Bernard-Jean Marfan. The syndrome is an autosomal dominant disease, which is a certain pattern of inheritance that is characteristic of some genetic diseases (read more on the genetics of Marfan Syndrome on my other blog post). A syndrome is a collection of physical features which, when they occur together, enable a physician to recognize a certain condition. Symptoms vary greatly from person to person and may affect many different physical areas of the body:

Skeletal:

• Tall, thin physique with disproportionately long limbs (armspan usually greater than height), fingers, and toes 
• Lax ankles (loose ankle ligaments) and flat feet
• Scoliosis (spinal curve)
• Narrow chest, with either a cave or a pigeon (protruding) deformity
• Joint hypermobility
• Common hernias (a sac formed by the lining of the abdominal cavity)
• Ballooning/widening of the dural sac (the membranous sac that encases the spinal cord within the bony structure of the vertebral column)

Cardiovascular:

• Dilation of the ascending and sometimes descending aorta
• Leak of aortic or mitral valves
• Aneurysm and dissection of aorta

Respiratory:

• Collapse of the lungs (pneumothorax)
• Bronchiectasis
• Emphysema and asthma

Ocular:

• Dislocation of lens
• Myopia (nearsightedness)
• Unstable refraction of light in eye
• Retina detachment
• Glaucoma (damage to eye nerves over time)

 Dental:

• high arched palate
• crowded teeth
• narrow jaw

Although people with Marfan Syndrome often have these similar physical features, some will have very mild symptoms, while others have severe ones—even within the same family. This variable expression makes it difficult to predict how the disease will progress in any affected individual once diagnosed. These individuals are usually tested at a young age if their parents are known to have the syndrome. However, by the unlikely chance that a person develops the disease through spontaneous mutation, they will most likely be tested whenever symptoms become noticeable, which can range from the age of a young child to a young adult. To be properly diagnosed, they will have to visit multiple doctors specializing in different areas.
A geneticist may ask whether any family members have the syndrome and take blood tests to check for the gene that causes Marfan Syndrome. A cardiologist (a doctor who specializes in the heart and blood vessels—the cardiovascular system) may listen to the heart for murmur, order x-rays of the chest, take an electrocardiogram (also known as EKG, which measures electrical impulses in the heart) and an echocardiogram (a test that uses sound waves to produce a picture of the heart) to check the size of the aorta and to make sure the valves are functioning well. An orthopedist (a doctor who specializes in corrections of the skeletal system) may check for curvatures of the spine and breastbone, joint problems, and any other bone abnormalities. An ophthalmologist (doctor specializing in the eyes) may dilate the pupil with special drops, then use a slit lamp to detect lens dislocation and other eye problems.

Once diagnosed, patients with Marfan Syndrome will have to undergo treatment. Although there is no cure, doctors can successfully treat just about all of the symptoms. Medications such as beta blockers (read more about these here) and ACE inhibitors (read more about these here) are usually prescribed. These medications work to reduce blood pressure and wear and tear on the blood vessels, delaying the process of aortic dilation. For those with milder symptoms, glasses or contact lenses may be prescribed to treat nearsightedness, and a back brace may be required if scoliosis develops. However, in cases where these symptoms progress, surgery is needed. Possible surgeries include procedures to repair or replace the damaged parts of the heart if the aorta widens too much or if there is valve leakage, if the lens of the eye becomes extremely dislocated, or if scoliosis and chest wall problems become severe enough. 

Life is not the same for all who have Marfan syndrome. Many lead relatively normal lives that only require regular checkups, while others may need constant medical care. However, there are general limitations, such as eye, heart, and joint problems. People with Marfan Syndrome must also avoid putting extra stress on the heart, as well as activities that risk cardiovascular exhaustion, muscle strain, and impact to the chest.


After this beginning and basic exploration, I felt much more informed on Marfan Syndrome, and much readier to tackle further in-depth research.