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Published on: September 15, 2018
The genetics of autosomal dominant familial hypercholesterolemia
Sharon Anderson1,2, Christina Botti1
1Division of Medical Genetics, Rutgers Robert Wood Johnson Medical School, Rutgers Health, Child Health Institute of New Jersey, New Brunswick, New Jersey.
Insights
Familial hypercholesterolemia (FH) is a common genetic disorder causing high LDL cholesterol and early heart disease. Early diagnosis and treatment are crucial for managing this underdiagnosed condition.
Area of Science:
- Genetics
- Cardiology
- Metabolic Disorders
Background:
- Familial hypercholesterolemia (FH) is a prevalent genetic disorder.
- It results from inherited defects in LDL receptor function, leading to extremely high cholesterol levels.
- This significantly increases the risk of premature coronary artery disease.
Purpose of the Study:
- To provide a comprehensive overview of autosomal dominant FH.
- To discuss disease prevalence, diagnostic criteria, genetic factors, and treatment strategies.
- To highlight challenges in genetic testing and the importance of expert management.
Main Methods:
- Review of existing literature on autosomal dominant FH.
- Analysis of clinical diagnostic criteria and genetic variants.
- Inclusion of a case study to illustrate diagnostic complexities.
Main Results:
- FH is characterized by elevated total and LDL-cholesterol levels.
- Diagnosis is supported by family history, early-onset atherosclerosis, or tendon xanthomas.
- Genetic testing interpretation can be challenging, underscoring the need for experienced clinicians.
Conclusions:
- Autosomal dominant FH is underdiagnosed and undertreated.
- Accurate genetic test interpretation and experienced provider involvement are vital for effective diagnosis and management.
- Timely intervention can mitigate the risk of premature cardiovascular events.
Abstract:
Familial hypercholesterolemia (FH) is one of the most common genetic conditions. Affected individuals are unable to metabolize cholesterol due to inherited changes in the low-density lipoprotein (LDL) receptor, which impairs the ability to metabolize cholesterol, resulting in extremely high levels of cholesterol that leads to premature coronary artery disease. Autosomal dominant FH is caused by variants in several genes, which may present as heterozygous FH (less severe) or homozygous FH (more severe). Clinical diagnosis may be more likely when there is a family history of two or more first-degree relatives with total and LDL-cholesterol (LDL-C) level elevations, a child is identified, or the affected individual or close relatives have tendon xanthomas and/or progressive atherosclerosis. This article provides an overview of autosomal dominant FH, including disease prevalence, clinical diagnostic criteria, genetic variants, diagnostic testing, pathognomonic findings, and treatment options. It also shares a brief case, which highlights challenges associated with genetic test interpretation and the importance of including experienced providers in the diagnosis and treatment of this underdiagnosed and often untreated or undertreated genetic condition.
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