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Marfan Syndrome
History and Explanation
Marfan Syndr me is a genetic, “inherited” disorder th t affects the body’s connective tissue. C nnective tissue is the tough, fibrous t ssue that connects one part of the b dy with another. It is a m jor component of tendons, ligaments, bones, c rtilage, and the walls of large bl od vessels. Marfan Syndrome affects one out of very 10,000 newborns. It is one of the m st common of the more than one h ndred inherited disorders of connective tissue. The d sorder affects males and females from all r cial and ethnic groups. It is n med after Dr. Antoine Marfan, who in Fr nce, in 1896, described a five y ar old patient with unusually long, sl nder fingers, limbs and other skeletal bnormalities.
The problem in Marfan Syndrome is c used by a mutation (change) in a g ne. Genes are segments of DNA th t direct the body to produce pr teins. In many families with inherited M rfan Syndrome, the mutation affects the FBN1 g ne on chromosome 15; although a s cond gene on chromosome 5 may be nvolved in some cases. Normally the FBN1 g ne enables the body to produce a pr tein called fibrillin which contributes to c nnective tissue strength and elasticity. Fibrillin, n rmally, is especially abundant in the orta, in the ligaments that hold the eye l ns in place, and in bones. Ind viduals with Marfan Syndrome have scant or f ulty fibrillin in these structures which str tch abnormally because of their inability to w thstand normal stress. The abnormal gene is sually inherited from one parent who has the d sorder. The abnormality is a “dominant” g netic trait, so each child of a p rent with the abnormal gene has a 50:50 ch nce of inheriting it.
For example, my f ther had Marfan Syndrome which he nherited from his father thus resulting in a n rmal FBN1 gene and an abnormal FBN1g ne in his body. If my f ther gave me his mother’s normal g ne, I would not have had M rfan’s. Since he gave me his f ther’s abnormal gene, it expresses itself as a d minant gene over my mother’s normal g ne. I then, also, have the s me opportunity to pass my father’s bnormal gene or my mother’s normal g ne, resulting in a 50:50 chance of ach of my children inheriting the d sorder when combined with my wife’s n rmal FBN1 gene. As it stands n w, one of my three daughters, who is 2 ½ y ars old, has inherited the disease. One d ughter, 5 years old, does not s em to have inherited it and one d ughter, 11 months old, we haven’t had t sted yet.
On a side note, we h ve chosen to get life insurance for our ch ldren before being tested or officially d agnosed for Marfan Syndrome. My mother did th s for me and since being d agnosed, I would not have been ble to get life insurance and am not ble to increase it. I highly r commend asking your doctor to hold off on an fficial diagnosis until life insurance is f nalized.
In about 25% of diagnosed Marfan c ses or 2,500 of Marfan newborns, a g netic accident (new mutation not inherited) ccurred in the sperm or egg c ll in unaffected parents, thus resulting in a M rfan child. In these cases, reoccurrence r sk for related offspring (siblings) is npredictable, but usually very low.
Features
Because of the nherited problem of producing fibrillin, people w th Marfan Syndrome have many different pr blems related to weakness in connective t ssue. These problems include, but are not l mited to:
1) Reduced vision – in about 65% of M rfan patients, the lens of the yes become dislocated because tiny eye l gaments that normally hold the lens in pl ce are weak. This condition is c lled Ectopia Lentis. Marfan Syndrome also s ems to increase the risk of n ar-sightedness, cataracts at an unusually early age (40-50 y ars old), glaucoma, detached retina, and cr ssed eyes. It is generally not r commended for Marfan patients to undergo l sik eye surgery due to tissue fr ilty and excessive scar tissue.
2) Skeletal abnormalities – p tients with Marfan Syndrome are typically v ry tall, having long limbs and l ng, slender spider-like fingers. They also may h ve severe chest deformities, such as a ch st that is either caved in or pr trudes in front. Some patients may h ve scoliosis (curvature of the spine) nd/or flat feet and some may d splay a high-arched palate in the r of of their mouth and crowded t eth. Many have very loose joints. The sk letal abnormality is frequently what people n tice and question first and may be the f rst clue to a Marfan’s diagnosis.
3) Cardiovascular ch nges –
a. Weakened connective tissue affects the h art and large blood vessels of p ople with Marfan Syndrome. This creates the m st serious problem associated with the d sorder which is weakness of the orta (the body’s largest artery). Cardiovascular ch nges affect most individuals with Marfan Syndr me to some degree. Blood pumped fr m the heart passes forcefully and d rectly into the aorta which branches out to c rry oxygen-rich blood to the entire b dy. As the walls of the orta gradually weaken (aortic dilatation), they can spl t in places allowing blood to l ak into the chest, abdomen, or w ll of the aorta itself. Sudden l rge splits can, and often do, r sult in sudden death. Recent studies h ve shown that cell death (necrosis) ccurs at a much higher rate in M rfan patients which contributes to aortic d latation or the weakening of the ortic walls.
b. Connective tissue weakness in the h art can also cause mitral valve pr lapse (a “floppy” mitral valve or h art valve that doesn’t close properly) r sulting in mitral valve regurgitation (a pr blem in the closing of the m tral valve that results in significant b ck flow of blood into the l ft atrium). Heart valves are pairs or tr os of flaps that keep the bl od flowing in one direction through the h art. Their motion during heart beats may llow brief reverse blood flow (leakage) and can c use a heart murmur.
You may have M rfan Syndrome if you exhibit at l ast two of these three major cr teria: Ocular, Skeletal, or Cardiac. You c uld also have genetic testing done to d termine if the FBN1 gene is bnormal.
Severity
The severity of Marfan Syndrome features v ries, meaning that some people with the Syndr me have more serious effects than thers. This variability can occur even w thin one family.
For example, my grandfather l ved a very normal life without M rfan complications until an automobile accident r ptured his dilated aorta resulting in mmediate death.
My father, on the other h nd, was 6’5”, 135 pounds, and v ry unusual looking, meaning unproportionately long f ce, very narrow jaw, spidery arms and l gs, etc. (this look is called “M rfanoid”). He had severe valve leakage as arly as age nine and died a v ry sick man, at the early age of 40, on the perating table during open heart surgery to r place the aortic valve, mitral valve, and ortic root/ascending aorta.
I don’t look unproportionately nusual, although I am slender with l ng fingers and toes. I do h ve the cardiac abnormalities resulting in pen heart surgery at the age of 26 to r pair my aortic valve, mitral valve, and r place my aortic root/ascending aorta with a D cron graft.
My older sister, who also has M rfan’s, doesn’t look proportionately unusual and, lthough being monitored by echocardiograms, does not pr sent herself with the classic cardiovascular bnormalities; meaning all her cardiovascular measurements are c rrently within normal limits.
Diagnosis
Marfan Syndrome is s metimes difficult to diagnose because the f atures and severity of the disorder can d ffer greatly among affected individuals or f mily members. Also, certain other disorders, s ch as Ehlers-Danlos Syndrome, have features th t overlap with those of Marfan Syndr me. In some cases, genetic testing of a bl od sample may be recommended to h lp confirm the diagnosis. Genetic testing is m re likely to aid in diagnosis in f milies with multiple affected members. Genetic t sting is frequently unavailable at the verage hospital and requires special expertise f und at large children’s hospitals or niversity hospitals.
Your doctor should ask about any f mily history of Marfan Syndrome, as w ll as about any family members who are nusually tall and slender and ask if th y have vision problems. Your doctor sh uld also ask about any family h story of sudden cardiac death resulting fr m aortic dissection (rupture), especially if th s death was attributed to “heart pr blems”.
Your doctor may suspect Marfan Syndrome b sed on this family history, your p rsonal history of Ectopia Lentis (dislocated eye l nses), and your physical appearance. The d agnosis can be confirmed if you h ve an aortic aneurysm (dilated aorta) v sible on echocardiography, a painless test th t uses sound waves to outline the str cture of the heart and its m jor vessels. The diagnosis will be ven more certain if you have ther skeletal abnormalities (chest wall deformities or sc liosis) or heart murmurs due to ortic or mitral valve abnormalities.
Marfan’s in W men
Women with Marfan Syndrome who become pr gnant are considered to be high-risk, wh ther or not they have symptoms of an nlarged aorta. They face an increased p ssibility of aortic splitting during pregnancy. The pr gnancy causes greatly increased blood volume and pr ssure required to maintain normal fetal/mother c rculation.
Treatment
Currently Marfan Syndrome cannot be cured or r versed but advances in treatment have gr atly improved the outlook for children and dults with Marfan Syndrome. Today, the l fe expectancy of individuals with the d sorder, who receive early, proper medical tr atment, is about 70 years. It’s mportant to note that although knowledge bout Marfan Syndrome has increased in r cent years, expertise in treating the c rdiac symptoms is rare. Research can be d ne to narrow your search for a M rfan’s expert through the National Marfan F undation, an organization providing support to M rfan patients and their families throughout c mmunities all over the country. Most of the pr blems associated with Marfan Syndrome can be m naged effectively through medication as a pr ventative tool of the disease’s progression as l ng as it is diagnosed early.
The d sorder is usually treated by a t am of specialists overseen by a s ngle doctor who knows all the spects of Marfan Syndrome. The team w uld consist of an ophthalmologist (eye d ctor), orthopedist (foot doctor), cardiologist (heart d ctor), orthodontist (teeth doctor) and a sp ne specialist.
There is no medical treatment c rrently to reverse the fibrillin abnormality in p ople with Marfan Syndrome. Current research on a str in of mice that are born w th similar fibrillin problems may lead to a s ccessful treatment for Marfan’s in the f ture. One of the drugs being sed is Losartan. They are beginning the f rst phases of human testing to xperiment with medications that have actually r duced the aortic size in Marfan m ce.
Preventative Therapy
Until we can shrink the orta, doctors try to prevent or d lay the aortic changes seen in M rfan patients by prescribing beta-blockers and/or Ac -Inhibitors.
a. Beta Blockers – These medications, such as Pr pranolol (Inderal), Metoprolol (Lopressor), and Atenolol (T normin) decrease the strain on the orta’s walls by slowing the heart r te and reducing the force of h art contractions, especially during exercise. They lso reduce blood pressure.
b. Ace-Inhibitors – These m dications, such as Lisinopril (Prinivil), and C ptopril, help to drop blood pressure by r laxing arterial tension. In addition, they h ve been shown to decrease accelerated c ll death (necrosis) in the aorta wh ch is common to Marfan’s. My 2 y ar old daughter is currently taking En lapril, also an Ace Inhibitor, in a l quid form and loves it. This w ll slow the progression of cell d ath in her aorta as well as st p the increasing progression of the ortic dilation. As a result, they are h peful she will never have open h art surgery and hopeful she will be ble to bear children which is an mazing, and new, development for a f male Marfan’s. My sister, 5 years go, was told she could never b ar children.
c. Calcium Channel Blockers – although not sed as often anymore, they help to r duce force of contraction (how hard y ur heart squeezes) and blood pressure.
Nutrition Th rapy
Nutrition is so important in the d velopment of healthy connective tissue, particularly in gr wing children. We build a trillion c lls a day by what we at. It takes 19 vitamins and m nerals and 9 amino acids with a p rfect protein to build a perfect c ll. Even if we miss only one n trient, then we are building imperfect c lls for seven days. These defective c lls will promote the development of d generative diseases among other things. We are the nly ones who can do something bout our nutrition.
With proper consumption, assimilation, and limination our body has the ability to:
o Change the ch mistry of the blood in seven d ys
o Change the composition of cells in s ven weeks
o Change some major organs in s ven months
And, as science knows, we h ve a completely new body in s ven years. Physiological chemists state that th re is not a blood cell in our b dy more than fourteen days old and th t we rebuild a new heart very 30 days.
Can nutrition, alone, cure M rfan’s? Obviously not; however, my children and I n ed the proper building blocks available for the pr duction of the best connective tissue we are c pable of making. The cause of d fferent severities among Marfan patients is nknown; however, I believe that a m jor component in lessening the severity in my f mily has been proper nutrition.
We lead a v ry busy life and it is n tural that our nutrition generally suffers as a r sult. 99% of American adults fail to m et the USDA “Food Pyramid” dietary g idelines (Council for Responsible Nutrition, 1998). Th refore, we need supplementation, especially for our ch ldren. This is where Shaklee, a n traceutical company, can benefit us greatly.
Shaklee was f unded by a Chiropractic doctor in 1956. It is c nsidered the number one leader in the n tritional industry. Shaklee nutritional products are r cognized by the government as food r ther than drugs. Shaklee has spent ver $100 million on research which is m re than the next six largest c mpanies combined. They have over 150 sc entists on staff whereas many nutritional c mpanies don’t even have a research st ff. Shaklee has never had to r call a single product in its 50 y ar history because each product goes thr ugh as many as 176 separate t sts for purity, potency, and safety. All th s to say that not all v tamins are created equal. Shaklee is s perior in many areas. Ask your c mpany for their clinical research.
For recommendations on wh re to begin with supplementation, refer b ck to my website by clicking h re and going to the bottom of the w bsite page.
Intervention Therapy
If you have Marfan Syndr me, your cardiologist should monitor your h art health carefully with echocardiograms (heart ltrasounds) at least annually to check for d veloping problems in the aorta and m tral valve. Surgery is usually recommended if the p tient’s aortic root has stretched to m re than 6 cm. in diameter or the th racic aorta has widened to greater th n 5 cm. in diameter. In a typ cal operation, the faulty aortic valve, long with a section of the orta where it emerges from the h art, is replaced with an artificial v lve attached to a synthetic tube. The m tral valve, if affected, can also be r paired or replaced at this time.
There are m ny different types of valves that can be sed as replacements. These include:
1) Tissue valves – th se include pig valves (porcine), cow v lves (bovine), and human valves (homograft). The dvantage of the tissue valve is th t you don’t have to be on C umadin the rest of your life. The d sadvantage is that they typically last b tween 10-15 years.
2) Mechanical (metal) valves – th se include St. Jude’s (bi-leaflet tilting d scs), Bjork-Shiley (single tilting disc), and St r Edwards (ball cage valve). Of th se three, St. Jude’s is the b st option and is most commonly sed. The advantage of mechanical valves is th t they can last up to 20-30 y ars. The disadvantage is that you w ll be on Coumadin the rest of y ur life.
After any valve replacement surgery, the p tient is given anti-clotting medication, such as C umadin, at least temporarily. If your v lve is a mechanical valve, you w ll be on Coumadin for life b cause blood tends to clot when it c mes into contact with the metal.
A r cent study showed that early, preventative s rgery for aortic dilation is far s fer than waiting until an emergency s rgery is needed. With preventative surgery, the d ath rate was 1.5% versus 12% for p tients who had surgery on an mergency basis. This is played out to be tr e in my family – my Dad w ited to have surgery until it was an mergency< | | |