Screening for genetic mutations in children and adolescents with dyslipidemia: importance of early identification and implications of missed diagnoses

ABSTRACT

Introduction: Disorders of lipid metabolism caused by genetic mutations, acquired risk factors and risk conditions, or both, are common in children. While some manifest clinical signs and symptoms, children with genetic mutations such as familial hypercholesterolemia are asymptomatic and generally of normal weight. Nonetheless, life-long elevation of cholesterol plays a key role in the initiation and progression of atherosclerosis, starting in childhood, and increases risk of premature cardiovascular disease-related events, such as myocardial infarction and stroke.

Areas covered: Genetic mutations and acquired risk factors and conditions that cause dyslipidemia are outlined. Current guidelines for screening, interpretation of test results, implementation of therapy and monitoring are reviewed, and the role of genetic testing is discussed.

Expert opinion: In addition to a heart healthy lifestyle, those with inherited disorders of lipid metabolism often benefit from timely medical intervention to reduce or postpone morbidity and avoid premature mortality. The ability to identify this vulnerable population creates the opportunity to prevent development of premature cardiovascular disease-related events by effective management of genetic and acquired risk factors. As universal cholesterol screening of children becomes standard practice, healthcare professionals need to be familiar with the care and follow-up of those at moderate to high risk.

KEYWORDS:

• Dyslipidemia
• children
• atherosclerosis
• cardiovascular disease
• Mendelian randomization
• hypercholesterolemia
• hypertriglyceridemia

Article highlights

• Inherited disorders of lipid metabolism are common.

• Epidemiologic, genetic, basic science and clinical research suggests that cumulative risk exposure over a lifetime leads to accelerated development of atherosclerosis.

• Although cardiovascular disease events rarely occur during childhood or adolescence, elevated levels of cholesterol play a key role in the initiation and progression of atherosclerosis. This is especially true in those with familial hypercholesterolemia, beginning in childhood.

• Genetic traits characterized by life-long elevation of cholesterol are associated with atherosclerosis and increased risk of premature cardiovascular disease-related events, while those with genetically low levels of cholesterol are associated with a significant lowering and longer life expectancy.

• In addition to a heart healthy lifestyle, in those with inherited disorders of lipid metabolism, medical intervention is often necessary to reduce or postpone morbidity and avoid premature mortality.

This box summarizes key points contained in the article.

Acknowledgments

The authors would like to acknowledge Karen Keller, Dena Hanson, and Lynn Harmon for their assistance in preparing and editing this manuscript.

Declaration of interest

D Wilson is a speaker for the Osler Institute, Synageva Biopharma Corp, Insulet Corp, and Alexion, has participated in an advisory board for Aegerion, Alexion and Synageva Biopharma Corp, and received research funding from Merck Sharp & Dohme and Novo Nordisk Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.