NURS 505 Week 2 Genomics and Genetics Presentation on Familial Hypercholesterolemia Example

One Family, One Variant, Many Hearts: Applying Graduate Genomic Competencies to Familial Hypercholesterolemia

Slide 1: Title

• One Family, One Variant, Many Hearts
• Applying graduate genomic competencies to familial hypercholesterolemia
• NURS 505, Liberty University

Speaker notes: This presentation applies the genomic competencies expected of nurses with graduate degrees to familial hypercholesterolemia, a common inherited condition that is usually missed.

Slide 2: A Family Story

• Father: heart attack at 44
• Daughter, 19: LDL 230 mg/dL on a college physical
• No one connected the two

Speaker notes: Consider a composite family. A father had a heart attack at 44 and was treated with a statin. Years later the father's daughter, at 19, had an LDL cholesterol of 230 on a routine physical and was told to eat better. No one asked about the father's history, and no one tested the rest of the family. A single question about family history could have identified a lifelong risk in every relative.

Slide 3: What the Condition Is

• Inherited disorder of LDL clearance
• LDL high from birth, early heart disease
• Most common single-gene disorder in humans

Speaker notes: Familial hypercholesterolemia is an inherited disorder in which the body cannot clear LDL cholesterol normally, so levels are high from birth and atherosclerosis begins early. Mirzai et al. (2023) describe it as the most common monogenic disorder in humans, affecting millions worldwide, with lack of timely diagnosis as its greatest challenge.

Slide 4: The Genetics

• Variants in LDLR, APOB or PCSK9
• Autosomal dominant: each child has a 50% chance
• Two variants: homozygous, much more severe

Speaker notes: Most cases are caused by variants in the LDL receptor gene, with fewer in APOB and PCSK9. Inheritance is autosomal dominant, so a parent who carries one variant passes it to half of their children on average. People who inherit two variants have homozygous disease, with extremely high LDL and heart disease in childhood; in a Saudi cohort of 88 patients with homozygous disease, reverse cascade screening of relatives identified additional affected family members (Alsagheir et al., 2025).

Slide 5: Competency: Risk Assessment Through Family History

• Ask about early heart disease in relatives
• Three-generation pedigree
• LDL at or above 190 mg/dL in an adult is a red flag

Speaker notes: The graduate competencies begin with the ability to elicit and interpret a family history and identify genetic risk (Greco et al., 2012). A three-generation pedigree, like the genogram in this course's first assignment, can show the pattern of early heart attacks across generations, and an adult LDL of 190 or higher should prompt the question of familial hypercholesterolemia.

Slide 6: Clinical Clues on Examination

• Tendon xanthomas, especially Achilles
• Corneal arcus before 45
• Usually no physical signs at all

Speaker notes: The physical examination, the focus of this course, can provide clues such as thickened Achilles tendons or tendon xanthomas and a corneal arcus in a younger adult, but most patients have no signs, so the history and LDL level matter more (Bickley et al., 2021).

Slide 7: Competency: Genetic Testing

• Confirms the diagnosis and identifies the variant
• Enables precise testing of relatives
• Informed consent and counseling first

Speaker notes: Graduate nurses should understand indications for genetic testing and ensure informed consent (Greco et al., 2012). Testing confirms the diagnosis and identifies the family's specific variant, which makes testing relatives straightforward. Counseling before testing covers what a result means for the patient and for relatives.

Slide 8: Why Patients Decline Testing

• Doubt that results change care
• Worry about the emotional toll and insurance
• Testing uptake low even when free

Speaker notes: In a 2026 qualitative study of 24 people offered testing in Singapore, Lenin et al. (2026) found that both tested and untested participants valued testing but that many doubted its added value, especially if already taking a statin, and some feared the psychological and social consequences. Nurses need to address these concerns directly.

Slide 9: Competency: Cascade Screening

• Start with first-degree relatives of the index case
• Each relative has a 50% chance
• Most efficient way to find new cases

Speaker notes: Cascade screening tests relatives of a person with a confirmed diagnosis, beginning with parents, siblings and children. In our composite family, the daughter's diagnosis should lead to testing of the daughter's brothers and sisters and the father's siblings, and eventually their children.

Slide 10: Is Screening Worth the Cost?

• 21 economic studies, 62 strategies
• Cascade screening cost-effective in 78% of studies
• Main driver: long-term cost of lipid lowering

Speaker notes: Marquina et al. (2024) reviewed 21 cost-effectiveness analyses of 62 screening strategies. Cascade screening was cost-effective in 78% of the studies, opportunistic screening in 85% and population-wide screening in 60%, with the long-term cost of lipid-lowering treatment the most common factor driving results.

Slide 11: Children in Affected Families

• Screen children of affected parents early
• Lipoprotein(a) may add risk
• Treatment can begin in childhood

Speaker notes: Because exposure to high LDL begins at birth, children of affected parents benefit from early screening. A 2026 systematic review examined lipoprotein(a), a separate genetic risk factor, in children and young people with familial hypercholesterolemia and found that its distribution and added significance in the young are still being clarified, which supports measuring it as part of a full risk assessment (Priestley-Barnham et al., 2026).

Slide 12: Management Basics

• High-intensity statin, often with ezetimibe
• PCSK9 inhibitors when goals are not met
• Lifelong treatment and follow-up

Speaker notes: Treatment aims for substantial LDL lowering early in life. A high-intensity statin is the foundation, often combined with ezetimibe, and PCSK9-targeted therapies are added when targets are not met (Mirzai et al., 2023). Lifestyle matters but cannot overcome the genetic defect alone.

Slide 13: Ethical and Family Communication Issues

• Who tells relatives, and how
• Privacy versus duty to warn
• Genetic Information Nondiscrimination Act limits

Speaker notes: Genetic results belong to families as well as individuals. The competencies expect nurses to support patients in sharing information with relatives while respecting privacy, and to explain protections such as the federal law against genetic discrimination in health insurance and employment, along with its limits for life insurance (Greco et al., 2012).

Slide 14: Mapping the Competencies

• Risk assessment: family history and LDL (slide 5)
• Genetic testing and counseling (slides 7 and 8)
• Referral, family communication, ethics (slides 9 and 13)

Speaker notes: This slide maps the presentation to the competency domains, from risk assessment and interpretation through testing, referral and the ethical dimensions of family information.

Slide 15: The Nurse's Actions

• Ask about early heart disease in every family history
• Flag adult LDL at or above 190 mg/dL
• Start the conversation about testing relatives

Speaker notes: For advanced practice nurses, the actions are simple: ask the question, recognize the number and begin cascade conversations. Each step can change the course of heart disease in a whole family.

Slide 16: References

• Alsagheir et al. (2025); Bickley et al. (2021); Greco et al. (2012)
• Lenin et al. (2026); Marquina et al. (2024)
• Mirzai et al. (2023); Priestley-Barnham et al. (2026)

References

Alsagheir, A., Abdullah, I. A., Albitar, M., Aljaser, A., Alansari, R., Ali, A., Aldamouni, M., Alhosainy, Z., Mohamed, R., Jaamour, H., Alhuthil, R., Al-Hamoudi, S., Aldayel, A., Aljumaa, M., Khamaj, Y., Mcrabi, A., Alquayt, M., & Al-Ashwal, A. (2025). Homozygous familial hypercholesterolemia in a high-consanguinity population: Insights from a Saudi cohort. Journal of Clinical Lipidology, 19(4), 1055-1063. https://doi.org/10.1016/j.jacl.2025.04.185

Bickley, L. S., Szilagyi, P. G., Hoffman, R. M., & Soriano, R. P. (2021). Bates' guide to physical examination and history taking (13th ed.). Wolters Kluwer.

Greco, K. E., Tinley, S., & Seibert, D. (2012). Essential genetic and genomic competencies for nurses with graduate degrees. American Nurses Association and International Society of Nurses in Genetics.

Lenin, C., Chan, F. H. F., Lim, P. X. H., Ang, G., Nastar, A., Daccord, M., Print, E., Pek, S., Subramaniam, T., & Griva, K. (2026). FH genetic testing in preventive cardiology: Unpacking challenges and enablers beyond cost. BMC Health Services Research, 26(1). https://doi.org/10.1186/s12913-026-14133-w

Marquina, C., Morton, J. I., Lloyd, M., Abushanab, D., Baek, Y., Abebe, T., Livori, A., Dahal, P., Watts, G. F., & Ademi, Z. (2024). Cost-effectiveness of screening strategies for familial hypercholesterolaemia: An updated systematic review. PharmacoEconomics, 42(4), 373-392. https://doi.org/10.1007/s40273-023-01347-7

Mirzai, S., Chevli, P. A., Rikhi, R., & Shapiro, M. D. (2023). Familial hypercholesterolemia: From clinical suspicion to novel treatments. Reviews in Cardiovascular Medicine, 24(11), Article 311. https://doi.org/10.31083/j.rcm2411311

Priestley-Barnham, L., Humphries, S. E., Wray, J., & Khan, T. (2026). Distribution of lipoprotein(a) concentrations in children and young people with familial hypercholesterolemia (FH) compared to those without FH: A systematic review and narrative synthesis. Atherosclerosis, 419, Article 120823. https://doi.org/10.1016/j.atherosclerosis.2026.120823