Author: Elizabeth A.M. Frost, MD
What Is It?
Named after Antoine Marfan, a French pediatrician who first described the disorder in 1896, Marfan syndrome (MFS) is a connective tissue disorder of autosomal dominant inheritance, affecting the cardiovascular, skeletal, and ocular systems.1 Pulmonary involvement is less frequent. The gene linked to MFS was identified by Francesco Ramirez in 1991.2 The disorder is characterized by mutations in the FBN1 gene on chromosome 15, which encodes fibrillin-1, a glycoprotein component of the extracellular matrix essential for its formation, including the synthesis and maintenance of elastic fibers.3 It is also involved in dysregulation of cytokine-transforming growth factor beta (TGFbeta) signaling.
The incidence of MFS is approximately two to three in every 10,000 individuals. The syndrome occurs in all races and ethnic groups, and is equally distributed between the sexes. Individuals are affected to varying degrees. Each parent with the condition has a 50% risk for passing on the genetic defect. Most people with MFS have another affected family member. About 15% to 30% of all cases are due to de novo genetic mutation.
Diagnostic criteria of MFS were agreed upon internationally in 1996, and are based on family history and a combination of major and minor indicators of the disorder, for example, four skeletal signs with one or more signs in another system such as ocular and cardiovascular. Other conditions are associated with MFS, including aortic aneurysm, aortic valve abnormalities, mitral valve prolapse, and palpitations; degenerative disk disease, arachnodactyly, osteoarthritis, osteopenia, scoliosis, hypermobile joints, pectus excavatum, deviated septum, and tall stature; cataracts, glaucoma, lens dislocation, retinal detachment, and myopia; obstructive lung disease, pneumothorax, and sleep apnea; hernias, reflux disease, and adrenal insufficiency; and malocclusion, micrognathia, temporomandibular joint (TMJ) dysfunction, high arched palate and narrow face.4
The Ghent nosology of 2010 revised diagnostic criteria further.5 If there is no family history of MFS, the criteria are an aortic root Z-score of 2 or greater and ectopia lentis, the FBN1 mutation, or a systemic score of greater than 7 points; or ectopia lentis and the FBN1 mutation with aortic pathology. If there is a family history of MFS, the criteria are an ectopia lentis systemic score of 7 or more points. The systemic score depends on finding, among other features, wrist and thumb sign, long fingers, pectus carinatum deformity, pes planus, scoliosis, mitral valve prolapse, myopia, characteristic facial features, and increased height.
Even though there is no cure for MFS, life expectancy has increased significantly. Cardiology consults are necessary to slow the progression of aortic dilation by lowering the heart rate and blood pressure. Beta-blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors are usually prescribed. Angiotensin II receptor blockers (ARBs) reduce TGF-beta and can inhibit the growth of aortic dilation, but a recent study demonstrated similar cardiac outcomes between ARBs, losartan and atenolol.6
Vision-related difficulties may impair the ability of a patient with MFS to read consent forms. Scoliosis may adversely affect pulmonary function. Preoperative respiratory therapy is indicated. Symptoms related to mitral valve prolapse, including atrial fibrillation (dyspnea, dizziness, orthopnea) need to be evaluated, and cardiac consultation should be sought. Anxiety and panic attacks should be prevented with benzodiazepines. Antibiotic prophylaxis is recommended for patients at risk for endocarditis. Heart rate should be controlled. Difficult intubation should be anticipated because of a high arched palate and proneness to TMJ dislocation. Ready help and a difficult airway cart should be available. Patient positioning must be done carefully as osteopenia and joint dislocation are not uncommon. Protection of long fingers to avoid trapping by the table is indicated. Intravenous access may require availability of ultr asound. A lax upper airway increases the likelihood of obstructive sleep apnea. Use of narcotics should be minimized and a multimodal analgesic approach employed.
Pregnancy presents a significant risk for aortic dissection, which is often fatal even when rapidly treated, even in patients who had few or no cardiac complaints preconceptionally.7 Frequent echocardiographic assessment is essential to assess the aortic root diameter. Vaginal delivery is often possible.
- Hao W, Fang Y, Lai H, et al. Marfan syndrome with pneumothorax: case report and review of literatures. J Thorac Dis. 2017;9(12):E1100-E1103.
- Brown P. Marfan syndrome linked to gene. New Scientist. July 27, 1991. www.newscientist.com/?article/?mg13117793-100-science-marfan-syndrome-linked-to-gene. Accessed March 12, 2018.
- Kusick V. The defect in Marfan syndrome. Nature. 1991;352(6333):279-281.
- Pyeritz RE. Etiology and pathogenesis of the Marfan syndrome: current understanding. Ann Cardiothorac Surg. 2017;6(6):595-598.
- Loeys BL, Dietz HC, Braverman AC, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010;47(7):476-485.
- Lacro RV, et al. Atenolol versus losartan in children and young adults with Marfan’s syndrome. N Engl J Med.2015;372(10):980-981.
- Goland S, Elkayam U. Pregnancy and Marfan syndrome. Ann Cardiothorac Surg. 2017;6(6):642-653.