The first part of treatment centers on the need to minimize the effects of valve leakage and optimize ventricular function. Medications such as beta blockers (such as carvedilol or metoprolol XL), angiotensin converting enzyme inhibitors (ACE-inhibitors, such as captopril or enalapril), or angiotensin receptor blockers (ARBs, such as losartan or irbesartan) are often used. If there are clear signs of heart failure, a class of medications called diuretics may be added to eliminate excessive fluid through the kidneys. Other medications, such as digoxin, can be used to boost heart contractions.

Signs that heart failure is progressing include a build-up of fluid in the lungs, often associated with shortness of breath, poor feeding, poor weight gain, reduced exercise capacity, and/or difficulty lying flat comfortably. Often, medical treatment alone is not sufficient to control the effects of valve regurgitation. When this occurs, valve repair or replacement (most often the mitral valve) may be considered. If a mechanical valve is used, the patient needs to be on blood-thinning medication for the rest of their life. On rare occasions, patients in heart failure are considered for heart transplant for the potential of an improved long-term outcome; however, complications in other systems, such as lung disease and musculoskeletal issues may affect candidacy for heart transplant. Furthermore, there are long-term risks related to heart rejection and the use of drugs to suppress the immune system. In addition, the remaining aorta remains at risk for enlargement and tear (dissection).

A second part of treatment in neonatal Marfan syndrome is to slow aortic dilation to reduce the risk of aortic dissection. In children with neonatal Marfan syndrome, aortic dilation is often severe and rapidly progresses. Medications used to slow aortic growth overlap with those used for regurgitation/function; these include beta blockers and angiotensin receptor blockers (ARBs). Frequent echocardiography and/or cardiac MRI may be recommended to monitor the size and function of the aorta. If the aorta is growing rapidly or reaches a certain dimension despite medical treatment, surgical aortic replacement may be considered. This, however, is exceedingly rare in infancy or early childhood. Vascular repair may also be considered if the enlarged aorta or pulmonary artery is pressing on adjacent structures, such as the airways that carry air into and out of the lungs.

Breathing problems in infants with neonatal Marfan syndrome can also relate to the general weakness or floppiness of the airways in these children which causes the airways to collapse inappropriately. The use of supplemental oxygen or other forms of breathing support, such as masks or breathing tubes, may be required. Infants with neonatal Marfan syndrome are at risk for destruction and widening of the airspaces in the lungs (emphysema), obstruction of the breathing tubes, atelectasis (incomplete expansion of lung tissue), pneumothorax (air around the lung causing compression of the lung), and increased blood pressure in the lungs (pulmonary hypertension). A pulmonologist (lung specialist) may be required to help manage these conditions.

In rare circumstances, urgent involvement of eye specialists (ophthalmologists) is needed in early infancy to address eye conditions that can cause a severe or complete loss of vision. In some cases, eye surgery is necessary.