Familial Marfan Syndrome

Authors:
Syed A. A. Rizvi, PhD, MS, MBA
Larkin Community Hospital, South Miami, Florida

Zafar Qureshi, MD, and Sehrish Sikandar, MBBS
UHI CommunityCare Clinic, Miami, Florida

Mohammad J. Latif-Jangda, MD
Nova Southeastern University, Fort Lauderdale, Florida

Muhammad A. Rehan, MBBS, MPH
Florida Department of Health, Fort Lauderdale, Florida

Rodel A. Reyes, MD
City College, Fort Lauderdale, Florida

Citation:
Rizvi SAA, Qureshi Z, Sikandar S, Latif-Jangda MJ, Rehan MA, Reyes RA. Familial marfan syndrome. Consultant. 2018;58(7):190-191.

A 62-year-old man presented to the clinic with a chief concern of tiredness and dyspnea. He stated that he had been experiencing shortness of breath for years. The tiredness was acute and had begun 3 months before presentation.

History. Review of his medical history revealed a previous diagnosis of Marfan syndrome. The patient denied fever, chills, nausea, vomiting, and diarrhea and reported no history of the use of tobacco or illicit substances. One of the patient’s school-aged daughters also had been seen recently at the same clinic for a chief concern of dyspnea during physical education class; her dyspnea had begun approximately 1 year ago and had become progressively worse.

NEXT: Physical Examination

Physical examination. At presentation, the man was noticeably thin and tall and was visibly short of breath. His blood pressure was 107/60 mm Hg, pulse rate was 66 beats/min, and respiratory rate was 17 breaths/min. The patient was 188 cm tall and weighed 68 kg, with a body mass index of 19.3 kg/m².

Consistent with the classic signs of Marfan syndrome, the patient had marked pectus excavatum (Figure 1), long, slender fingers and toes (ie, arachnodactyly) (Figure 2), and obvious signs of ligamentous laxity. (The patient’s daughter had similar physical findings, including arachnodactyly [Figure 3]). Further examination of the man revealed a high-arched palate and crowded teeth, pes planus, and scoliosis. On cardiovascular auscultation, a grade 4/6 systolic murmur was heard, most prominently over the fifth intercostal space, midclavicular line.

The remainder of the physical examination findings were unremarkable.

Figure 1. The patient had marked pectus excavatum, a classic sign of Marfan syndrome.

Figure 2. The patient had arachnodactyly, a classic sign of Marfan syndrome.

Figure 3. The patient’s daughter also had classic signs of Marfan syndrome, including arachnodactyly.

NEXT: Diagnostic Tests

Diagnostic tests. Laboratory test results included the following: red blood cell count, 6.39 × 10⁶/µL (reference range, 4.7-6.1 × 10⁶/µL); white blood cell count, 8100/µL (reference range, 3800-10,800/µL); and hemoglobin, 12.2 g/dL (reference range, 12.0-16.9 g/dL). Levels of electrolytes, calcium, glucose, albumin, aspartate aminotransferase, alanine aminotransferase, creatinine, and blood urea nitrogen were within normal ranges.

Results of chest radiographs revealed cardiomegaly and hyperinflated lungs with chronic emphysematous changes. Results of a 2-dimensional color flow Doppler transthoracic echocardiogram (TTE) revealed a reduced ejection fraction of 50%. There was concomitant moderate to severe mitral and aortic valve regurgitation. The aortic root was noted to be dilated on TTE; as a result, a computed tomography (CT) scan of the chest with intravenous contrast was obtained, the results of which showed no evidence of significant dilation of the ascending aorta or aortic root.

NEXT: Discussion

Discussion. Marfan syndrome (named after French pediatrician Antoine Marfan, who first described it)¹ is an autosomal dominant disorder resulting from a mutation of FBN1, located on band 15q21.1.² This gene is responsible for the synthesis of the protein fibrillin-1, needed for the production of the microfibrils whose job is to provide flexibility to the connective tissue.^3,4 It occurs in as many as 20 in 100,000 individuals and mainly affects the heart, aorta, eyes, lungs, and skeleton.^5,6

Affected individuals tend to be tall, to have disproportionally large hands, and to have either pectus carinatum or pectus excavatum, as was noted in our patient’s case. However, the degree of genetic variability makes definitive diagnosis difficult. Therefore, it is common for patients to get a Marfan syndrome diagnosis in adulthood after they experience a life-threatening complication related to the condition. One of the most serious and potentially fatal complications of Marfan syndrome is gradual aortic root dilation leading to aortic dissection. Also common is mitral valve prolapse with regurgitation, which can eventually lead to congestive heart failure (CHF).⁷

Although there is no treatment for Marfan syndrome, medical management can reduce the severity of symptoms and stop further damage. The use of β-adrenergic blockers is the most common option, while calcium channel antagonists and angiotensin-converting enzyme inhibitors have also been investigated.⁸

The early diagnosis of Marfan syndrome is imperative to improve patients’ prognosis and quality of life. It also allows further investigation to identify other family members who might be affected by the condition. The early detection of Marfan syndrome in our patient’s daughter will likely improve her quality of life. She frequently undergoes screening with TTE to monitor her thoracic aorta and the condition of her heart valves. Conversely, the late diagnosis of Marfan syndrome in the father highlights the limitations on quality of life that this condition can impose. Despite being on optimal medical management with metoprolol and furosemide, he continues to have symptoms of CHF secondary to valvular heart disease, for which he is evaluated monthly.

REFERENCES:

1. Marfan AB. A case of congenital deformation of the four limbs, more pronounced at the extremities, characterized by elongation of the bones with some degree of thinning [in French]. Bull Mem Soc Med Hop Paris. 1896;13(3):220-226.
2. Gillis E, Kempers M, Salemink S, et al. An FBN1 deep intronic mutation in a familial case of Marfan syndrome: an explanation for genetically unsolved cases? Hum Mutat. 2014;35(5):571-574.
3. McKusick VA. The defect in Marfan syndrome. Nature. 1991;352(6333):279-281.
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