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INTRODUCTION:
Marfan syndrome is a genetic disorder of the connective tissue. This syndrome is
inherited as a dominant trait, carried by the gene FBN1, which encodes the
connective protein fibrillin-1. Marfan syndrome has a range of expressions, from
mild to severe. The most serious complications are defects of the heart
valves and aorta. It may also affect the lungs, the eyes, the dural sac surrounding
the spinal cord, the skeleton and the hard palate. Patients with marfan syndrome
are at risk for catastrophic aortic complications and mortality. We discuss a case
of 26 years old male patient, presenting with acute chest pain and was
diagnosed to be a case of marfan syndrome with severe AR with aortic
dissection. This case is unique as the patient is on conservative treatment and
doing well for last three years, the incidence of such cases reported is very
limited.
CASE REPORT:
A 26 yrs old male presented to us with chief complaints of acute chest pain, of
sudden onset, on left side while having his meals. This pain was tearing in nature
and was radiating to the back. This pain was not associated with any vomiting or
excessive sweating or any loss of consciousness. On examination, patient was
tall in stature and thin in built. His BP was 140/70 mm Hg and pulse was 82/min.
On general physical examination, long slender limbs were observed with long
fingers and toes. He was having increased lower extremity to trunk ratio. There
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was high arched palate, elongated hands and feet, hyperflexible joints and flat
foot.
On cardiac examination, early diastolic and decrescendo murmur was heard,
which was best heard in the third left intercostal space and was radiating along
the left sternal border. There was no evidence of mitral valve prolapse.
On
abdominal examination, renal bruit was also present.
His routine laboratory investigations were in normal limit. His ECG was showing
features of left ventricular hypertrophy. Chest X-Ray showed widening of the
mediastinum (Fig1). X-Ray of hands and feet showed elongated fingers and toes,
respectively (Fig 2). Patient was sent for echocardiography which showed
evidence of severe aortic regurgitation. His cardiac MRI showed a flap in the
posteromedial wall in the ascending aorta and in the upper abdominal aorta
(Fig.3). Immediate surgery was advised but was refused by the patient. Patient is
being managed on beta blockers for last 3 years now.
DISCUSSION:
Marfan syndrome (MFS) is a well-defined genetic defect with both a structural
and functional propensity for aortic dissection. Severe elastic fiber degeneration
occurs because mutant fibrillin is unable to bind calcium. Sinus dilatation and
increased wall stiffness elevate pulse pressure on the structurally attenuated
aortic wall. Impaired mechanotransduction (nitric oxide production) causes failure
of flow-mediated vaso-dilation with increased wall stress and cardiac workload.
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Marfan syndrome is a heritable disorder of the connective tissue with a
prevalence of ≈1 in 3000 to 5000 individuals. Marfan syndrome affects males and
females equally and the mutation shows no ethnic or geographical bias.
Marfan syndrome is an autosomal dominant, multisystem disease characterized
by long bone overgrowth and other skeletal abnormalities, dislocation of the
ocular lens (ectopia lentis), pneumothorax, decreased skeletal muscle mass,
mitral valve prolapse, and dilatation of the aortic root. Antoine Bernard-Jean
Marfan first described the syndrome in 1896 in a young patient with peculiarly
long and thin digits (subsequently termed arachnodactyly), elongated limbs
(which he termed dolichostenomelia), and congenital contractures of multiple
joints.
The most common cardiovascular complication in patients with MFS is
progressive aortic root enlargement initially occurring at the sinuses of
valsalva. Cardiovascular manifestations in MFS also include valvular disease
involving the mitral valve, aortic valve, or both. Mitral valve prolapse is the most
prevalent valvular abnormality, affecting 35% to 100% of patients [1]. Other
cardiovascular manifestations may include mitral annular calcification, pulmonary
artery dilatation, tricuspid valve prolapse and branch vessel dilatation and
dissection. Because of the varying symptoms and signs of aortic dissection
depending on the initial intimal tear and the extent of the dissection, the proper
diagnosis is sometimes difficult to make.
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The diagnosis cannot always be made by history and physical signs alone. Often
the diagnosis is made by visualization of the intimal flap on a diagnostic imaging
test. The common tests used to diagnose an aortic dissection include a CT scan
of the chest with iodinated contrast material and an aortogram or magnetic
resonance angiogram (MRA) of the aorta. Trans-oesophageal echocardiography
can also prove to be useful. Chest radiography may reveal widening of the
mediastinum, obliteration of the aortic knob, depression of the left mainstem
bronchus, loss of the paratracheal stripe, and tracheal deviation. A blood D-dimer
level less than 500 mcg/mL may be able to rule out the diagnosis of aortic
dissection alleviating the need for further imaging [2].
Prevention of aortic dissection is paramount for the marfan patient. Lifelong ßblockade and elective aortic root replacement (at 5.0 cm) transform the long-term
outlook. The outlook for patients with marfan syndrome is transformed by elective
aortic root replacement [3]. Aortic root dilatation begins in infancy with a maximal
rate of diameter increase during the ages of 6–14 years. After this, root
enlargement slows, but the increase in radius and decreased wall thickness
causes mural stress to rise dramatically.
Beta adrenergic blockade retards the rate of dilatation and risk of dissection by
reducing wall stress. In those individuals who develop side effects and therefore
cannot tolerate β-blockade, verapamil can be considered a second-line therapy
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[4]. Other medications might be needed to further minimize blood pressure
without slowing the heart rate, such as ACE inhibitors and angiotensin II receptor
antagonists.
The goal of treatment is to slow the progression of aortic dilation and damage to
heart
valves
by
eliminating arrythmias,
minimizing
the heart
rate,
and
minimizing blood pressure. Exercise restriction represents a second approach to
reduce hemodynamic stress in MFS [5]. If the dilation of the aorta progresses to
a significant diameter aneurysm, causes a dissection or a rupture, or leads to
failure of the aortic or other valve, then surgery (possibly a composite aortic valve
graft or valve-sparing aortic root replacement) becomes necessary.
The traditional threshold that prompts the consideration of prophylactic aortic root
replacement in patients with MFS has been predicated on aortic size and
recommended when the diameter reaches 5.0 cm.
To conclude, since marfan syndrome is not curable, detailed lifelong medical and
surgical treatment can greatly prolong life in marfan syndrome.
REFERENCES :
1. Van Karnebeek CD, Naeff MS, Mulder BJ, Hennekam RC, Offringa M.
Natural history of cardiovascular manifestations in Marfan syndrome.Arch
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2. Shimony, A; Filion, KB, Mottillo, S, Dourian, T, Eisenberg, MJ (2011-0415). "Meta-analysis of usefulness of d-dimer to diagnose acute aortic
dissection". The American journal of cardiology 107 (8): 1227–34.
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3. Gott V.C., Pyeritz R.E., Cameron D.E., Green P.S., McKusick V.A.
Composite graft repair of Marfan’s aneurysms of the ascending aorta:
results in 100 patients. Ann Thorac Surg 1991;52:38-45.
4. Rossi-Foulkes R, Roman MJ, Rosen SE, Kramer-Fox R, Ehlers KH,
O'Laughlin JE, Davis JG, Devereux RB. Phenotypic features and impact of
beta blocker or calcium antagonist therapy on aortic lumen size in the
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Exerc. 1998;30:S387–95.
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