SAMIKSHAHEARTCARE 57698d5b9ec66b0b6cfb5b6b False 534 1
background image not found
update image not found
SAMIKSHA HEART AND DIABETIC CARE ''CONNECTIVE TISSUE DISORDERS'' ''Marfan Syndrome'' Marfan syndrome is a systemic connective tissue disorder with a frequency of 2 to 3 in 10, 000. The disorder is characterized by manifestations involving the cardiovascular, skeletal, and ocular systems. Current diagnostic criteria are based on involvement of above organ systems and family history. Cardiovascular manifestations include mitral valve prolapse, progressive aortic root enlargement, and ascending aortic aneurisms, possibly leading to aortic regurgitation, dissection, or rupture. Some characteristic skeletal manifestations of this syndrome include disproportional increase of linear bone growth resulting in malformations of the digits (arachnodactyly), craniofacial abnormalities, pectus excavatum/carinatum, and scoliosis. A common ocular involvement is severe myopia and lens dislocation in one or both eyes (ectopia lentis). Marfan syndrome is an autosomal dominant disorder caused by fibrillin-1 gene mutations encoding for the extracellular matrix protein fibrillin (Fbn-1). Fibrillin is an integral component of both elastic and nonelastic connective tissue. The mechanism of fibrillin mutation in Marfan syndrome remains unclear. However, animal models of Fbn-1 have demonstrated a role of TGF-beta signaling. In some patients with phenotypes similar to Marfan syndrome but without fibrillin- 1 gene mutations, TGF-beta receptor mutations have been identified, suggesting a significant role of TGF-beta pathway in the pathogenesis of Marfan syndrome features. Aortic root involvement remains the leading cause of death in patients with Marfan syndrome. Echocardiography is recommended to routinely screen and to follow aortic root dilation. In addition, all first-degree relatives of the family should have screening echocardiography. Patients should be advised against strenuous exercises. Medical therapy for Marfan syndrome includes beta-blockers to reduce myocardial contractility and pulse pressure. Animal models of Marfan syndrome have demonstrated a possible benefit of losartan in preventing progression of the disease by inhibiting the TGF-beta pathway, and this therapy is the subject of an active clinical trial. Elective aortic root replacement remains the therapy of choice once the aortic root becomes significantly enlarged. Marfan patients who become pregnant need to be counseled not only about the 50% chance of transmitting the disease but also the substantially increased risk of aortic rupture/dissection during and after pregnancy. Important components of Marfan syndrome counseling are consideration of contraception and pregnancy management. Loeys-Dietz Syndrome Recently, an aortic aneurysm syndrome has been identified with TGF-beta receptor mutations. Loeys-Dietz syndrome is an autosomal dominant condition with a characteristic triad of arterial tortuosity/aneurysm, hypertelorism, and bifid uvula or cleft palate. There is significant overlap with Marfan syndrome, and the management is similar in terms of cardiovascular manifestation. Early, elective, surgical intervention should be considered in patients with significant aneurysmal dilation of the aorta. Some clinicians have argued for much earlier surgical intervention for the dilated aorta in this condition, compared with Marfan syndrome, since there appears to be a much greater risk of rupture and dissection at earlier ages and smaller aortic sizes. Pregnancy counseling is also an integral part of therapy. Ehlers-Danlos Syndrome Ehlers-Danlos syndrome is a group of disorders that affect connective tissue development due to defects in collagen and connective tissue biosynthesis. Prevalence of the disease is about 1 in 400, 000 people in the United States. Cardiac manifestations include spontaneous rupture of medium to large sized arteries including the aorta. Frequently, extracardiac presentations include hyperextensible skin and hypermobile joints. To date, 11 types of the disorder have been recognized, but collagen defects have been described in only 6 types. Although all types of Ehlers-Danlos syndrome affect the joints and the skin, clinical features vary by type. Different features characterize each type of the syndrome. Type IV carries the poorest prognosis, especially due to spontaneous ruptures of arteries and organs. Extreme caution needs to be taken if surgical intervention is needed due to weakened connective tissue structures. Many genes, including ADAMTS2, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, PLOD1, and TNXB, have been implicated in the pathogenesis of Ehlers- Danlos syndrome, but the predominant cardiovascular concern exists in the Type IV vascular form of Ehlers-Danlos associated with mutations in the COL3A1 gene and aortic dilation/aneurysms. Other less commonly associated anomalies include ventricular septal defect, patent ductus arteriosus, bicuspid pulmonic valve, and Ebstein’s anomaly. Bicuspid aortic valve has been shown to demonstrate familial clustering. However, identifying culprit genes have been difficult due to variable penetrance and the common nature of the disorder.
2 3