6 - Clinical Evaluation for Genetic Testing and Secondary Causes of Dyslipidemia

Abstract

Dyslipidemia today is typically identified biochemically and then defined according to the main biochemical disturbance. For mild-to-moderate deviations from the normal range, the etiology is a combination of a polygenic susceptibility component aggravated by secondary factors. For severe deviations in the lipid profile, a monogenic etiology is more likely, although a discrete single-gene cause frequently cannot be found; the phenotype is often caused by polygenic susceptibility aggravated by exposure to key secondary factors. A family history of dyslipidemia or atherosclerotic cardiovascular disease (ASCVD) can suggest a monogenic etiology. With any severe lipid deviation, clinical examination should focus on detecting specific manifestations of syndromic monogenic dyslipidemias. Because of increased ASCVD risk in many patients with dyslipidemia, it is important to evaluate the cardiovascular system. With severe hypertriglyceridemia—either monogenic or polygenic in etiology—there is also increased risk of acute pancreatitis. For all patients referred with dyslipidemia, secondary causes must be ruled out, both clinically and through targeted laboratory investigations. Finally, recent progress in genetics suggests that for certain monogenic dyslipidemias, such as familial hypercholesterolemia and familial chylomicronemia syndrome, targeted genetic analysis may be helpful for clinical management.