Marfan Syndrome

Stretched

1

"Wonderful", you think irritably, as you check the delivery company's website. You arrived home a couple of days ago, after speaking at a conference, only to find out that the airline had misplaced your luggage. While they promised to courier it to you 'overnight', they appear to be stretching the term to its limit ... As you continue to silently curse the airline, your next patient walks in.


2

Sifani is a 28 year-old lady of Pakistani origin. She married David (who is a citizen of your country) just a couple of months ago, and is in the process of applying for permanent residency. Sifani carefully hands you an old and extremely battered card. As you go through it, you realize that it is a hospital record from her childhood, which shows her to have Marfan Syndrome.


3

Sifani tells you that she has not been followed up for almost one and a half decades now. However, after reading about her condition on the internet, she realized that it is important to see a medical professional, especially since she wishes to become pregnant. You congratulate the couple on their marriage, and remark that it was indeed a wise decision to seek medical care. Taking your time, you perform a thorough physical examination. During this, you see that almost all classical features of Marfan Syndrome are present, aside from increased joint mobility. You also note that her blood pressure is 110/80 mmHg, and that her pulse is 84 bpm and regular, with a good volume. No cardiac murmurs are audible. As so much time has passed since the initial diagnosis, you explain that you'd like to conduct some investigations for independent confirmation. Both Sifani and David unhesitatingly agree.


4

Your tests confirm the presence of Marfan Syndrome, as per the Ghent criteria. The FBN1 test is also positive. A transthoracic echocardiogram reveals aortic root dilatation of 5.1 cm, in association with mild left ventricular dilatation. Minimal mitral and aortic regurgitation is also present. A cardiac MRI confirms the echocardiographic findings.


6

Given the presence of left ventricular dilatation, you decide that 24 hour holter monitoring to exclude arrhythmias is justifiable. However, the continuous ECG tracing reveals no arrhythmias, a fact which is of much relief to the couple. They ask you if you are now able to advise Sifani about becoming pregnant.


8

You identify that the degree of aortic root dilatation necessitates aortic root replacement surgery, prior to Sifani becoming pregnant. After explaining this to the couple, you inform them of the necessity to consult a multidisciplinary team, including a cardiologist, regarding this matter.


9

After the couple leaves your office, you call up your colleagues and set up a meeting. Subsequently, your team discusses Sifani's case, and comes to the consensus that she indeed does require aortic root replacement surgery. You then coordinate with the cardiothoracic surgeon, and arrange a date for surgery.


10

The operation goes well, and Sifani recovers without complications. She is soon ready to be sent back home. Now that the cardiac issues have been dealt with, the couple are eager to know how to proceed ....


11

When you inform them that it is now possible to proceed with a pregnancy, both David and Sifani can hardly contain their joy at the good news. At the same time, you explain that Sifani needs to be started on certain drugs, some of which might be potentially teratogenic.


12

Which of the following drugs will you start Sifani on?

1. Propranolol
2. Atenolol
3. Metoprolol

13

After contemplating the side effect profiles of the potential drugs, you decide that Metoprolol is the best option. You carefully counsel the couple about the risks associated with pregnancy, and ask them to see you as soon as Sifani becomes pregnant. Sifani anxiously interrupts your explanation. "Excuse me doctor, but I need to know this now. Since this is a disease which is in my genes, will my child have it too?"


15

"Yes, I was just coming to that", you reply with a smile, and explain that the risk of her child having Marfan Syndrome is exactly 50%. You also make it clear that the clinical picture can be highly variable, and that it cannot be predicted based on the results of genetic testing. Sifani nods her understanding once you finish your explanation. As she highly enthusiastic to learn more about her disease and it's effects on pregnancy, you direct her to several useful patient resources.


16

At the end of the lengthy clinic visit, David and Sifani say that they understand the potential risks, but nevertheless intend to try for a pregnancy. Just a couple of months later, the happy couple are back in your office. Sifani missed her period last week, and her pregnancy test is positive. After congratulating them, you explain that you will now need to closely monitor Sifani throughout the pregnancy.


17

As the couple thank you and prepare to leave, your assistant asks you how Sifani's follow up should be scheduled.


19

You ask Sifani to visit your clinic every month, reemphasizing the importance of regular monitoring, as she has a high-risk pregnancy. Sifani attends her clinic appointments religiously, and takes a very active and enthusiastic role in her management.


20

During her next clinic visit, you decide that it is better to discuss the mode of delivery with the couple earlier, rather than later. After listening to your explanation on why this is important, they ask you which method you'd recommend ...


22

You explain why an elective Cesarean section is the best option, given the fetal and maternal risks and benefits. The couple agree with your decision, and subsequently, you make all necessary arrangements.


23

The remainder of Sifani's pregnancy is uneventful, and you deliver her baby via an uncomplicated Cesarean section at 38 weeks. Sifani and David are elated to have a healthy baby boy, and they cannot thank you enough for helping them start a family. Well done!


24

You decide that no other investigations are warranted right now, and archive Sifani's reports. Now that all the tests have been completed, Sifani and David eagerly await your opinion on how to proceed.


26

You decide that the degree of aortic root dilatation necessitates aortic root replacement surgery, prior to Sifani becoming pregnant, and inform the couple accordingly. The cardiothoracic surgeon agrees with your assessment, and subsequently Sifani is operated on.


27

Following an uncomplicated surgery and uneventful recovery, Sifani is discharged home. You inform her that it is now safe to try for a pregnancy, and start her on the appropriate medical management.


28

A couple of months later, the happy couple are back in your office. Sifani is pregnant! You congratulate them, and after emphasizing the importance of close monitoring, schedule their follow up appropriately.


33

As the weeks go by, Sifani is pushed to the back of your mind by other issues, such as other patients, clinical meetings and regular, boring hospital paperwork. One night, while going through a pile of paperwork at home, you receive a phone call from David. Sifani suddenly collapsed an hour ago, and expired before she could be taken to the emergency department. David says the doctors there mentioned something about "arrhythmias".


34

Suddenly, the Grim Reaper appears in front of you. "Thank you, old friend. Too bad that you didn't perform a holter study earlier", he whispers and fades away ....


35

You decide that further imaging via a transesophageal echocardiogram is important, and call up the cardiologist to schedule a study. However, after listening to you, your colleague smugly points out that this investigation is currently unnecessary. Chargrined, you hang up the phone and turn back to the couple ...


36

After reviewing the results of Sifani's tests, you decide that pregnancy is just too high risk a state. Even though you are as gentle as possible when conveying the bad news, she is distraught and bursts into tears .... A few days later, you receive a phone call from a very angry Sifani. After searching online and finding information at odds with your advice, she sought the opinion of another doctor. She in turn, after reviewing the results, found no reason to avoid pregnancy, although it is risky. Needless to say, neither Sifani nor anyone she knows will be seeking your medical opinion in the probable future ....


37

As you prepare to write out a prescription, a lecture from your days as a medical student suddenly flashes through your mind. As if in a dream, you hear your professor talking about the teratogenicity of the various types of beta blockers. You realize that there is still time to change your decision ....


38

As you inform your assistant about the follow up plan, she starts to look more and more puzzled. She gestures for you to move out of earshot of the couple, and whispers "Doctor, I believe that she needs monthly clinic visits and echocardiograms. You're lucky that you have me to remind you of this stuff!" "Thank you", you mutter embarrassedly, as you correct your mistake.


39

Just before opening your mouth, you suddenly recall what you read in your textbook of basic genetics, as a medical student. You remember that while Marfan Syndrome is indeed inherited in an autosomal dominant fashion, the clinical severity cannot be predicted. Perhaps you should change your answer ...


40

You explain that neither the probability of her baby having Marfan Syndrome, nor the resultant severity if so, can be predicted. Sifani looks at you with a puzzled expression. "Are you sure about that, doctor? That is not what I read online!" She suddenly pulls out her phone and navigates to a bookmark. "See - this website says that my baby might have Marfan syndrome half the time, but that the severity cannot be predicted" Sputtering, you say that, yes, Marfan syndrome is indeed transmitted in such a fashion, but as milder forms of the disease can be easily missed or misdiagnosed, in a practical sense, you consider it to be unpredictable. Sifani doesn't seem particularly convinced, while you yourself are only convinced of the fact that you need to brush up your knowledge of Marfan Syndrome ....


41

You tell Sifani and David that the best option is probably vaginal delivery under epidural anesthesia. However, even as the words exit your mouth, you feel uneasy. "Hold on - let me obtain an opinion from the anesthetist as well", you tell the couple, and call up your colleague. Your feelings prove to be accurate, as he immediately points out that an elective Cesarean section is preferable, given that Sifani has already undergone aortic root replacement. Hanging up the phone, you turn to the couple and say, "Well, the anesthetist recommends an elective Cesarean section. Given that he is the expert in this area, let's go ahead with his recommendation" Fortunately, they do not seem to notice the quaver in your voice ....


42

You decide that it is safe for Sifani to go ahead with the pregnancy, and prepare to convey the good news. However, you suddenly feel an uncharacteristic twinge of doubt. Isn't 5.1 cm of aortic dilation rather a lot? Excusing yourself, you perform a quick search for the relevant guidelines, and find out that prophylactic surgery is indeed indicated in patients with aortic root dilatation exceeding 50mm. Thanking your lucky stars, you turn back to the couple ...


43

You decide that it is safe for Sifani to go ahead with the pregnancy, and prepare to convey the good news. However, you suddenly feel an uncharacteristic twinge of doubt. Isn't 5.1 cm of aortic dilation rather a lot? Excusing yourself, you perform a quick search for the relevant guidelines, and find out that prophylactic surgery is indeed indicated in patients with aortic root dilatation exceeding 50mm. Thanking your lucky stars, you turn back to the couple ...