Ep 156: A 24-Year-Old Man with Noonan Syndrome and a Heart Murmur

Today’s episode discusses congenital heart disease and reviews murmurs associated with particular valvular disorders.

Read more on this topic in Harrison's.

Harrison's Principles of Internal Medicine, 22nd Edition

Transcript

[upbeat intro music] 

[Ms. Heidhausen] This is Katerina Heidhausen, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest content from the best minds in medicine. And now, on to the episode. 

[music continues] 

[Dr. Handy] Hi, everyone. Welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy. 

[Dr. Wiener] And I'm Dr. Charlie Wiener, and we're joining you from the Johns Hopkins School of Medicine. Welcome to today's episode: a 24-year-old man with Noonan syndrome and a heart murmur. Cathy, today we're spending time in the cardiology clinic. 

[Dr. Handy] Great. Who are we seeing today? 

[Dr. Wiener] Your patient is a 24-year-old man who was diagnosed with Noonan syndrome soon after birth. He's been followed by the cardiology clinic for some years with annual physical examinations and echocardiograms. Over the last four months, he's noticed some dyspnea on exertion that is new. He takes no medications. He lives independently and works as a web designer. He has not had any hospitalizations or acute illnesses in the past five years. 

[Dr. Handy] All right. Let's quickly review Noonan syndrome. It's an autosomal dominant genetic disorder. There are typical facial features with widely set eyes, low-set ears, and patients typically have short stature, congenital heart disease, bleeding dyscrasias, and skeletal malformations. Typically, intelligence is normal. Mutations in the PTPN1 gene are associated with about half of all cases of Noonan syndrome. 

[Dr. Wiener] Yeah, and that gets us to our question, which follows up on your mention of congenital heart disease. The question is asking, which of the following physical findings is most likely in this patient? Option A. is a holosystolic murmur at the apex radiating to the axilla; option B. is a late diastolic murmur at the apex; option C. is a midsystolic murmur in the right second intercostal space radiating to the neck; option D. is a midsystolic murmur at the left second intercostal space; or option E. is an early diastolic murmur at the right second intercostal space and the left sternal border. 

[Dr. Handy] I love that we're focusing on the physical exam today. Let's go through each murmur individually, and then we'll circle back to Noonan syndrome. 

[Dr. Wiener] Okay, that sounds good. Let's start with option A. the holosystolic murmur at the apex. 

[Dr. Handy] That murmur radiating to the axilla, or the back, is typical of mitral regurgitation. It's often described as a blowing sound. 

[Dr. Wiener] What about option B. the late diastolic murmur at the apex? 

[Dr. Handy] Option B. is describing mitral stenosis. The mitral stenosis diastolic murmur typically follows an opening snap, is low-pitched, and demonstrates pre-systolic accentuation. 

[Dr. Wiener] This is a great review. How about the midsystolic murmur in the right second intercostal space radiating to the neck? 

[Dr. Handy] That's aortic stenosis. It should be harsh and crescendo-decrescendo. Also, as aortic stenosis gets severe, the carotid impulse becomes smaller and later. That's the so-called pulsus parvus et tardus. 

[Dr. Wiener] Okay. Option D. the midsystolic murmur in the left second intercostal space? 

[Dr. Handy] That's typical of pulmonic stenosis. It is also typically crescendo-decrescendo and introduced with an ejection click. As disease gets more advanced, the pulmonic component of the second heart sound is reduced or absent. 

[Dr. Wiener] And finally, the early diastolic murmur at the right second intercostal space. 

[Dr. Handy] That's aortic regurgitation, and it's typically early diastolic, decrescendo, and blowing. 

[Dr. Wiener] Okay, great review. Now, which of those is associated with Noonan syndrome? 

[Dr. Handy] So getting back to the patient that we have here. So the cardiac valvular abnormality that we see most commonly in Noonan syndrome is pulmonic stenosis. So the answer is D. a midsystolic murmur in the left second intercostal space. 

[Dr. Wiener] That's not one of our more common murmurs. Why don't you tell me a little bit more about pulmonic stenosis? 

[Dr. Handy] Yeah, so first, Noonan syndrome is the second most common genetic cause of congenital heart disease after Down syndrome. Other less common causes of pulmonic stenosis are carcinoid syndrome, obstructing tumors, or large vegetations. Pulmonic stenosis is defined hemodynamically via systolic pressure gradient between the right ventricle and the main pulmonary artery. Right ventricular hypertrophy develops as a consequence of sustained obstruction to RV outflow, and systolic ejection is prolonged. 

[Dr. Wiener] How do patients typically present? 

[Dr. Handy] Patients with mild or even moderate pulmonic stenosis are usually asymptomatic, and first come to medical attention because of a heart murmur that leads to echocardiography. With severe pulmonic stenosis, patients may report exertional dyspnea or early-onset fatigue. Anginal chest pain from RV oxygen supply and demand mismatch and syncope may occur with very severe forms of obstruction, particularly in the presence of a destabilizing trigger. And these can be an arrhythmia, like atrial fibrillation, or a systemic process like fever, infection, anemia, or even pregnancy. 

[Dr. Wiener] What do you see on ECG in these cases? 

[Dr. Handy] The ECG will show right axis deviation, right ventricular hypertrophy, and right atrial enlargement in adult patients with severe pulmonic stenosis. 

[Dr. Wiener] Do we treat pulmonic stenosis? Our patient appears to be getting symptomatic. 

[Dr. Handy] Yeah, he'll likely need a cardiac catheterization. The major complication of worsening pulmonic stenosis is right ventricular failure which may be treated with diuretics. Provided there is not significant pulmonic regurgitation, percutaneous pulmonic balloon valvuloplasty is recommended for symptomatic patients with moderate or severe pulmonic stenosis. You can also do valvuloplasty for asymptomatic patients with a peak right ventricular to pulmonary artery gradient over 64 millimeters per mercury. Surgery may be required when the valve is dysplastic, as it's often seen in patients with Noonan syndrome. 

[Dr. Wiener] Great, so the teaching points of today's case are that Noonan syndrome is an autosomal dominant genetic syndrome that often has pulmonic stenosis as a manifestation. Pulmonic stenosis may progress to right heart failure, and may be treated with percutaneous or surgical interventions as needed. 

[Dr. Handy] And you can find this question and other questions like it on Harrison's Self-Review. And if you want to read more about this topic, you can go to the chapter on pulmonic stenosis and adult congenital heart disease. Visit the show notes for links to helpful resources, including related chapters and review questions from Harrison's, available exclusively on AccessMedicine. If you enjoyed this episode, please leave us a review, so we can reach more listeners just like you. Thanks so much for listening. 

[upbeat outro music]