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Cardiac involvement in genetic disease 

Cardiac involvement in genetic disease

Cardiac involvement in genetic disease

Thomas A. Traill



Expanded discussion of genetic causes of Noonan’s syndrome and Ellis-van Creveld syndrome, and pharmacological treatment in Marfan’s syndrome.

Updated on 27 Nov 2014. The previous version of this content can be found here.
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date: 26 April 2017

Many clinicians find themselves faced, from time to time, with a patient who has a family history of a known disorder, such as Marfan’s syndrome, or who has noncardiac features that suggest a syndrome.

Syndromic congenital heart disease

Down’s syndrome—25 to 50% have congenital heart disease, most characteristically atrioventricular canal defect.

Turner’s syndrome—causes two principal abnormalities of the aorta: coarctation and congenital abnormalities of the aortic valve (usually bicuspid).

Noonan’s syndrome—the most common heritable syndrome that characteristically causes congenital heart disease. Mutations in an intracellular signalling molecule protein tyrosine phosphatase SHP-2 account for 40% of cases. Characteristics include short stature, with a facies that is variously described as elfin or triangular, ocular hypertelorism, ears that are set low and rotated forwards, and webbing of the neck (the most obvious of the features that may lead to confusion with Turner’s syndrome). The most typical cardiac lesion is pulmonary stenosis.

Williams’ syndrome—caused by macrodeletions of chromosome 7 that include the elastin gene; includes the cardiovascular features of familial supravalvar aortic stenosis along with a characteristic facial appearance, with round, blue eyes, a distinctive stellate pattern of the irises, depression of the nasal bridge, outwards tilting of the nostrils, abnormal dentition, and big lips.

Other conditions—many other genetic syndromes have significant cardiac and vascular manifestations.

Connective tissue disorders

Marfan’s syndrome—caused by mutations of the fibrillin-1 gene (FBN1); characteristic cardiovascular findings are aneurysmal dilatation of the aorta, and occasionally other large arteries, and floppy mitral valve. Diagnosis is based on the presence of particular major or minor criteria, the major criteria being (1) aortic aneurysm, (2) lens subluxation, (3) characteristic skeletal abnormalities, and (4) dural ectasia. Aortic dissection and rupture are the commonest causes of death in untreated cases. β‎-Blockers are commonly given to slow the progression to aneurysm, but the benefit is probably modest and recent work suggests that angiotensin-II receptor blockers may be much more effective. Surgical replacement of the aortic root is generally recommended when the maximum measurement across the aorta reaches 5 cm.

Other conditions—the Ehlers–Danlos syndromes and many other genetic disorders have significant cardiac and vascular manifestations.

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