From the Guidelines
Marfan syndrome is the likely diagnosis for the combination of long extremities, midsystolic click, and small testes, and it follows an autosomal dominant inheritance pattern. This condition results from mutations in the FBN1 gene, which encodes fibrillin-1, a glycoprotein essential for elastic fiber formation in connective tissue 1. The defective fibrillin leads to weakened connective tissue throughout the body, explaining the characteristic skeletal abnormalities (long limbs, arachnodactyly), cardiovascular manifestations (mitral valve prolapse, aortic root dilation), and other features like small testes in males.
Key Features of Marfan Syndrome
- Long extremities
- Midsystolic click (indicating mitral valve prolapse)
- Small testes
- Autosomal dominant inheritance pattern
- Mutations in the FBN1 gene
Management and Prevention
Management includes regular cardiac monitoring with echocardiography, beta-blockers to reduce hemodynamic stress on the aorta, lifestyle modifications to avoid strenuous activities, and genetic counseling for family planning 1. Early diagnosis is crucial as preventive measures can significantly reduce the risk of life-threatening complications such as aortic dissection or rupture. The most recent guidelines recommend regular follow-up imaging studies at 6 months and then annually if stability is documented, with a focus on relating aortic measurements to normal values based on age and body surface area 1.
Importance of Early Diagnosis and Prevention
Given the high risk of life-threatening complications, early diagnosis and preventive measures are essential to improve outcomes in patients with Marfan syndrome. This includes a comprehensive evaluation of the cardiovascular, ocular, and skeletal systems, as well as genetic counseling for family planning. By prioritizing early diagnosis and prevention, healthcare providers can significantly reduce the risk of morbidity and mortality associated with Marfan syndrome.
From the Research
Clinical Manifestations
- Long extremities, midsystolic click, and small testes are clinical features that can be associated with Marfan syndrome, a systemic connective tissue disorder 2.
- Marfan syndrome is characterized by cardiovascular complications, including mitral valve prolapse (MVP), aortic insufficiency, dilatation of the aortic root, and aortic dissection 2, 3.
Mechanism of Inheritance
- Marfan syndrome is inherited in an autosomal dominant pattern with variable penetrance 2.
- The genetic locus responsible for Marfan syndrome has been identified, and research has begun to elucidate the molecular pathogenesis underlying this disorder 2.
Mitral Valve Prolapse
- Mitral valve prolapse is a common feature of Marfan syndrome, with a reported incidence of 40-80% 3.
- The echocardiographic features of MVP in Marfan syndrome have been well described, and the prevalence of MVP in Marfan syndrome is lower than previously reported 3.
- Patients with Marfan syndrome and MVP often have thicker mitral leaflets, more mitral regurgitation, and larger aortic root diameters compared to those without MVP 3, 4.
Management and Treatment
- The management and treatment of MVP in Marfan syndrome are crucial to prevent cardiovascular complications 5, 6.
- Concomitant mitral valve procedures during aortic root replacement do not seem to increase operative risk, and the short-term incidence of progressive mitral regurgitation is low in patients with MR grade ≤ 2 who do not undergo a concomitant MV procedure 4.