Marfan Syndrome: a Connective Tissue Disorder 

What maintains our bodies together? Apart from our bones and muscles we haveconnective tissue that supports the organs, holds the bodies cellsand give structure to the body; playing an important role in our development. This elastic fibrous tissue can also get sick and defective, some people might suffer from a disease known as Marfan Syndrome which is a very unique ‘’genetic hereditary disorder affecting fibers of the connective tissue inside body. ’’ (Mayo Foundation For Medical Education and Research, 2018). Different proteins compose the structure and different layers of the connective tissue; specifically the protein fibrillin-1 has to do with providing structural support in elastic and non-elastic connective tissues throughout the body therefore any change in the quantity of this protein will have its effect on the body along with the different organ systems. The etiology of this syndrome mainly occurs because of a mutation and/or malfunction in the gene that tells the body to produce more fibrillin-1.Men, women, and any ethnic group can have it. It is most likely to inherit from a parent or family member. Surprisingly, this genetic mutation can even occur with no family history present; when this occurs it is referred as a spontaneous mutation.

According to The Marfan Foundation, about 1 in 5,000 people have Marfan Syndrome and its a 50% chance that the gene will pass along each time the patient decides to become a parent. Individuals affected by this syndrome are born with it, but the features and complications do not present right away. It is usually a progressive disease but it affects differently in every patient. Some develop complications at birth, as small children or even adults. Every patient experiences the signs and symptoms differently, but one very common sign is a very elongated body frame. People with very lengthy arms, legs, and fingers in a disproportionately matter. Clinical manifestations include flat feet, flexible joints, pectus excavatum (breast bone sunken in) or pectus carinatum (protrusion of sternum), scoliosis, and kyphosis, high arched palate crowded teeth, heart murmurs, and extreme myopia (nearsightedness) can be present in this type of patient. Serious complications and disorders can occur in the pathophysiology of the disease that will affect the cardiovascular system, skeletal system, skin, eyes, and respiratory system. The most dangerous complication is when the the heart and blood vessels are involved, especially the aorta; large artery from the heart that supplies oxygenated blood. The incidence is so common that‘’heart and blood vessels problems affect 9 out of every 10 people diagnosed with Marfan Syndrome. ’’(Marfan Foundation, 2013).

The consequences of this are related to weak connective tissue which leads to a defective aorta giving opportunity to different cardiovascular complications like for example; aortic aneurysm, aortic dissection and valve malformation. Pulmonary complications are present as well and the risk is so high that everyone diagnosed with the disease should avoid to smoke at any cost. Respiratory dysfunctions include spontaneous pneumothorax, restrictive lung disease, emphysema, asthma, and sleep apnea. In the Marfan lung, a spontaneous pneumothorax can be recurrent and present in both lungs this occurs because the connective tissue present around the lungs is weak and any excessive pressure can cause harm. Restrictive lung disease is a result of muscle weakness or anatomy deformities that does not allow complete inhalation making it difficult to receive the appropriate amount of oxygen the body needs. The elastic properties of the lung are very important for the ventilation phase since it is the main component in determining inspiratory muscle effort required to breath. ‘’About 70% of people with Marfan Syndrome will have a restrictive respiratory profile creating and modifying respiratory mechanics. ’’ (Marfan Foundation, 2013). Mainly characterized by bronchoconstriction in the bronchioles, asthma can also occur and it is very important for a correct diagnosis because drugs used to treat asthma (beta-agonists) can interfere on the effects of beta-blockers, which are used as treatment to control aortic growth in people with Marfan Syndrome. Another respiratory complication is sleep apnea; even though it is more common in overweight patients, thin individuals who suffer from Marfan Syndrome can also suffer from this disorder. There can be a few causes but the main is that the connective tissue of the airwayis so loose that while sleeping tends to relax more and it can cause an obstruction. To be properly diagnosed certain symptoms and family history must be present. It is essential for an early accurate diagnosis to properly treat and manage the disease since it tends to worsen with age and the way it manifests in patients can vary widely with the signs and symptoms their relatives suffered. Genetic testing can be very helpful in establishing any risk of the incidence in patients; it also serves as a guideline when a physical exam with a doctor is not quite clear. There are also a number of tests to be done to see the severity of the disease and establish what system of the body is most affecting. One of the first tests will be an echocardiogram; which uses sound waves and real-time images of the heart. It is also useful to check condition and size of the aorta and heart valves. Another heart related test would be an electrocardiogram which checks the heart rate and heart rhythm. An eye examination should also be done since the connective tissues in the eyes will be out of place causing eye problems. ‘’More than half the people who suffer from Marfan Syndrome will have a lens dislocation; this is characterized by the focusing lens in the eye moving out of place because its supporting structure has weakened. There is no cure and the connective tissues that got broken will not heal or reattach. This can bring the consequence of a blurry vision which can be corrected with glasses. ’’(Harvard Health Publishing, 2014). To properly treat Marfan Syndrome the main step is to identify which body system is affecting the most. Since the incidence in cardiac issues is so high treatment usually involves medications to keep blood pressure low to reduce the stress on the aorta.

Regular monitoring is recommended to check any structural changes in the organs especially the heart. There is no definite cure, treatment focuses on living a long full life with the proper management and teaching the patient in identifying progression of the symptoms. As a last resort, surgical intervention is recommended to repair any deformity. ‘’There has been huge improvements in surgical interventions and pharmacological treatments developed in the last 15-20 years as a ‘’preventative’’ measure to reduce the mortality in Marfan patients. In the past, life expectancy was no more than 40 years old but because of the technology now available the average is 65-75 years old. ‘’(Uriarte, et al. , 2016).Surgical interventions include aortic repair, breastbone corrections, and eye surgeries. As a therapy option patient can wear contacts or glasses for their blurry vision or extreme nearsightedness. There is also a scoliosis treatment for children, it consists of wearing a custom made back bracewhich should be worn until growth is complete. Patient might need to make changes in life like avoiding any recreational or daily activity that might raise blood pressure and increases the risk for aortic dissection. A support group of people who suffer from the same disease is always healthy since patient feels identified and does not get depressed. A study focused on assessing the elastic mechanical properties of the respiratory system in marfan syndrome used mice asa model mimicking aspects of the syndrome in humans. The experiment revealed and found that Marfan mice exhibited an emphysema pattern with large alveolar interseptal distances as they aged through adulthood demonstrating an early lung impairment as an early symptom on the genetic disease. Future research should concentrate on alveolar structure and determine if the disease process emphysema actually develops or if the alveoli rupture because of the constant stretching of the already weakened connective tissue. Furthermore, a real life case of Marfan syndrome involved a 60-year-old Caucasian-female who complained of shortness of breath on exertion, extreme fatigue and lightheadedness for one year.

Gradual onset of fatigue and shortness of breath increased while doing her daily day activities, she says that she would have to stop to ‘’catch her breath’’. History of present illness includes atrial flutter, marfan syndrome, mitral valve regurgitation-severe, mitral valve prolapsed, palpations, pectus excavatum, scoliosis and tachycardia. Her past medical history includes cystitis chronic interstitial, nontoxic goiter, and osteoporosis. Patients family history; states that father had heart surgery. Father is alive at age of 86 and had a mitral valve replacement, congestive heart failure and an atrial fibrillation. Mother is also alive at age 82 and had an angina, she also has Marfan Syndrome as well. Social history; patient has living will. Currently retired and lives with husband. Surgical history includes: an appendectomy, tonsillectomy, hernia repair umbilical, hysterectomy, colonoscopy, and a cardiac catheterization.

Patient is allergic to Anaprox (Naproxen Sodium) and Levaquin (Levofloxacin), both produce a severe reaction. The patient interview revealed that she never smoked cigarettes denies any use of recreational illicit drugs. Says that last alcohol intake was 3 months ago. Patient is a Jehovah’s witness and if surgery has to be done for whatever reason she refuses whole blood, red blood cells, white blood cells, platelets, and plasma. She does admit she will receive fractionated products including: erythropoietin, recombinant factor 7, Keentra and cryoprecipitate and will also accept cell saver and hemodilution. On top of that, she describes herself as an easy bleeder, but when planning for surgeries she builds up on her hemoglobin and reserves significantly and it has proven to be effective for past surgeries. The review of symptoms: Extremities show no clubbing, cyanosis or edema. No varicosities or statis dermatitis. Lungs were clear to auscultation bilaterally with no wheezing, rhonchi, crackles or use of accessory muscles. Normal diaphragmatic excursion. Head, eyes, ears, nose, and throat had normal conjunctiva and lids. Extraocular movements are intact. Grossly normal auditory acuity. Oral mucosa is pink and moist. No septal deviation is present. Teeth have significant decay but gums and palate are in good condition. Neck is supple and no jugular venous distension is present. There is no thyromegaly and no lymphadenopathy. Also, trachea is midline. Heart has regular rate and rhythm. No rubs or gallops are detected. III/VI holosystolic murmur detected. Abdomen is soft, nontender, nondistended, without masses or organomegaly.

Vascularly, there is carotid, abdominal or femoral bruits. Peripheral pulses are intact in all 4 extremities. Musculoskeletal; gait is not observed. Scoliosis is present, chest and ribs protrude. There is good muscle strength and tone in all extremities. The skin is warm and dry without jaundice, rashes, bruising or lesions. No sensory or motor deficits. Patient is alert and oriented x3. Displays normal mood and affect. Answers questions appropriately.

The patient’s hematologic report reflects high hemoglobin of 20 g/dl. Patient states that she always builds it up because she is ‘’an easy bleeder’’. States that for previous surgeries has resulted very well. All other parameters were normal. Her electrolytes panel had hyperchloremia. All other parameters were within normal ranges. After taking her vital signs the following results were as following: oxygen saturation of 100%, respiratory rate of 25 breaths per minute which is a little bit high, blood pressure of 101/55mmHg, pulse of 75 beats per minute, and temperature of 98. 2 °F. Patient did not cough or produced any mucus. Currently she weighs 158. 5lbs and height is 68 inches. Special Tests that were done to her were revealed certain different things. On the chest x-rays no pleural effusions and no focal infiltrates were visualized. Minimal linear scarring or atelectasis in the inferior lingula and inferior medial right middle lobe. There is a 2mm right lower lobe pulmonary nodule. There is also a 6. 5mm nodule at the left base at the lateral costophrenic sulcus. There is a prominent dextroscoliosis of the midthoracic spine. Pectus excavatum is present. There is no cardiomegaly or pericardial effusion. Patient had catheterization which widely patent coronaries and severemitral regurgitation were discovered. An electrocardiography revealed a sinus rhythm, prolonged PR interval, abnormal R-wave progression and early transition. A carotid ultrasound was performed and revealed multiple bilateral nodules in the thyroid. Lastly, an echocardiogram revealed normal left ventricular cavity size with preserved systolic function and a severe prolapse of the posterior leaflet of the mitral valve, resulting in severe eccentric anteriorly directed jet of mitral regurgitation.

The three arterial blood gases realized were to see her state before and after the surgery since it was decided that she was going into surgery for a mitral valve repair. Her first one which was before the surgery revealed pH 7. 47, PaCo2 35. 0 mmHg, PaO2 99 mmHg, Hc03 of 20mEq/L, Spo2 98% and it was taken on room air. This one interprets as an uncompensated respiratory alkalosis. The second arterial blood gas was obtained and patient was already connected to the ventilator with an airway size of 8. 0 and 23 at the teeth towards the right side with a cuff pressure of 26 on the mode of Continuous Mandatory Ventilation in Volume Control, at a rate of 12, tidal volume of 500, PEEP of 8, and an FiO2 of 70%. The results were a pH 7. 42, CaO2 39 mmHg, PaO2 189 mmHg, and Hc03 25. 9 mEq/L; reveals a normal ABG with hyperoxygenation. Last arterial blood gas; pH 7. 41, PaCo2 34 mm Hg, PaO2 154 mmHg, and HcO3 21. 0 mEq/L which is a fully compensated metabolic acidosis with Hyperoxygenation. Before taking this blood gas the only changes made were PEEP had been reduced to 5 and the FiO2 to 50%. Her medication list included; Albuterol (Ventolin,Proventil) 2. 5mg for nebulizer PRN; is a bronchodilator that relaxes muscles in the airways and increases air flow to the lungs. Inhalation of this medication is used to treat or prevent bronchospasm in people with reversible obstructive airway disease. It is also used to prevent exercise-induced bronchospasm. Meperidine (Demerol) 25mg Injection; used to help relieve moderate to severe pain. It may also be used before and during surgery or other procedures. Meperidine belongs to a class of drugs known as opioid (narcotic) analgesics and is similar to morphine. It works in the brain to change how your body feels and responds to pain. Propofol 10mg/mL IV; Is a short-acting medication that results in a decreased level of consciousness and lack of memory for events. Its uses include the starting and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Diamox 5 mg/kg/dose once daily for 3 days; when people with Marfan get older, the tissue surrounding the brain and spinal cord may weaken and stretch.

This affects the bones in the lower spine causing pain. Her fifth medication was atenolol 25 mg twice per day IV push; is a beta-blocker used mainly for control of hypertension, angina, for management of acute myocardial infarction and occasionally for thyroid storm management. For treatment plan and therapies the main recommendation was a mitral valve repair or replacement via minimally invasive right thoracotomy. To procede the physician ordered a CT thorax with and without contrast to be obtained as soon as possible to review her anatomy for analysis relating to minimally invasive surgery. Recheck serial arterial blood gas in case of need of bicarbonate. Monitor intake/output and blood pressure. Will not use whole blood, red blood cells, white blood cells, platelets, and plasma. She does admit she will receive fractionated products including: erythropoietin, recombinant factor 7, Keentra and cryoprecipitate and will also accept cell saver and hemodilution. She does understand that she could die due to refusal. Patient understands and consents to the above procedures and wishes to proceed. After surgery, continue with usual medications to maintain blood pressure. Her prognosis is in a good position. It is believed that after the surgery patient will feel much better and due to the history of the patient which is compliant with her prescribed medications the outcome will be good.