Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) is a genetic disorder that causes high levels of LDL cholesterol (often referred to as “bad” cholesterol) from birth. This condition is inherited in an autosomal dominant pattern, meaning you only need to inherit one copy of the defective gene to develop FH. Here are some key points about familial hypercholesterolemia:



  • Genetic Mutation: FH is caused by a mutation in one of several genes responsible for cholesterol metabolism. The most common gene mutations linked to FH are the LDLR gene, the APOB gene, and the PCSK9 gene.


  • High Cholesterol: One of the main symptoms is significantly elevated LDL cholesterol levels from a young age.
  • Early Atherosclerosis: Due to high cholesterol, individuals with FH are at an increased risk of atherosclerosis, which is the narrowing and hardening of arteries.
  • Premature Heart Disease: This can lead to premature heart disease, heart attacks, and stroke, even in young individuals.


  • Cholesterol Levels: High LDL cholesterol levels are a primary indicator.
  • Family History: FH often runs in families, so a family history of early heart disease can be a clue.
  • Genetic Testing: Genetic testing can confirm the diagnosis by identifying mutations in the genes associated with FH.


  • Lifestyle Changes: This includes a heart-healthy diet, regular exercise, and avoiding tobacco.
  • Medication: Statins are commonly prescribed to lower cholesterol. Other medications, like PCSK9 inhibitors, can also be used.
  • Regular Monitoring: Due to the risk of heart disease, regular check-ups with a healthcare provider are essential.
  • Genetic Counseling: Particularly for family members who may be at risk, genetic counseling can help understand the inheritance pattern and implications.


  • Autosomal Dominant: FH follows an autosomal dominant pattern, meaning if a parent has FH, each child has a 50% chance of inheriting the condition.
  • Heterozygous vs. Homozygous: Heterozygous FH (inheriting one copy of the gene) is more common and tends to have milder symptoms. Homozygous FH (inheriting two copies of the gene, one from each parent) is more severe and rare.


  • Early Heart Disease: Without treatment, individuals with FH are at a very high risk of developing heart disease at a young age.
  • Xanthomas: These are cholesterol deposits under the skin, often seen in the tendons and joints.
  • Corneal Arcus: A ring-like opacity in the cornea, which can be a sign of high cholesterol.

Global Prevalence:

  • The World Health Organization (WHO) estimates that FH affects about 1 in every 200 to 250 people worldwide.
  • According to the European Atherosclerosis Society, the prevalence of heterozygous FH (the most common form) is approximately 1 in 200 to 1 in 250 individuals in most populations.
  • Homozygous FH, which is a more severe form, is rarer, with an estimated prevalence of around 1 in 160,000 to 1 in 300,000 individuals globally.

Prevalence in India:

  • Studies in India have reported varying prevalence rates. Some estimates suggest FH affects about 1 in 250 individuals, while others indicate it could be as low as 1 in 500.
  • Due to the large population size of India, even a prevalence of 1 in 500 would mean a significant number of people affected by this condition.

Factors Influencing Prevalence:

  • FH prevalence can vary based on genetic factors, ethnicities, and lifestyles.
  • Regions with higher rates of conditions related to FH (like premature coronary artery disease) often have a higher prevalence of FH.
  • Awareness and diagnosis rates also impact reported prevalence. In some areas, FH may be underdiagnosed or misdiagnosed, leading to lower reported prevalence rates.

Genetic testing plays a crucial role in the diagnosis and management of familial hypercholesterolemia. Here are some of its uses:


  • Diagnosis: Genetic testing can confirm a clinical diagnosis of FH. This is particularly important because symptoms alone may not be sufficient for a diagnosis, especially in cases where symptoms are mild or absent. Identifying the specific genetic mutation causing FH can also help in diagnosing other family members.
  • Risk Assessment: Genetic testing can identify family members who have inherited the FH-causing mutation. This allows for early screening and intervention, reducing the risk of cardiovascular disease.
  • Treatment Guidance: Different mutations can have varying effects on the severity of FH and response to treatment. Genetic testing can help tailor treatment plans. For example:
    • Some individuals may require more aggressive cholesterol-lowering therapies.
    • Knowing the genetic mutation can also guide the use of specific medications, such as PCSK9 inhibitors, which can be highly effective in FH patients.
    • Lifestyle modifications can also be more targeted based on genetic information.
  • Cascade Screening: Once a familial mutation is identified, other family members can undergo genetic testing to determine if they have also inherited the mutation. This cascade screening can identify individuals at risk and allow for early intervention.
  • Reproductive Planning: Individuals with FH who are planning to have children may opt for genetic testing to understand the risk of passing the condition to their offspring. This information can guide decisions about family planning and prenatal testing.
  • Research and Clinical Trials: Genetic testing contributes to research on FH by identifying new mutations and understanding how they impact cholesterol metabolism. This information is valuable for developing new treatments and participating in clinical trials.

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