Familial hypercholesterolemia (FH) follows an autosomal dominant inheritance pattern, meaning you only need one copy of the altered gene to develop the condition. If one parent has FH, each child has a 50% chance of inheriting it. About 1 in 313 people worldwide carry a mutation that causes FH, making it one of the most common genetic disorders.
The Dominant Pattern: One Gene Is Enough
Most inherited conditions people learn about in school are recessive, requiring two copies of a faulty gene (one from each parent) before symptoms appear. FH works differently. A single altered copy of the gene disrupts your body’s ability to clear LDL cholesterol from the bloodstream, leading to dangerously high levels from birth onward.
In practical terms, this means FH doesn’t skip generations the way recessive conditions often do. If your parent has it, the coin flip happens once for each pregnancy: 50% chance of inheriting the mutation, 50% chance of not. A parent without the mutation cannot pass it on at all. This predictable pattern is what makes family screening so effective once one person is diagnosed.
Which Genes Are Involved
Three genes account for nearly all dominant FH cases. The most common is the LDL receptor gene, responsible for 90 to 95% of cases. This gene provides instructions for building the receptors on liver cells that pull LDL cholesterol out of your blood. When the gene is mutated, your liver can’t clear LDL efficiently, and cholesterol accumulates.
The second gene, involved in 5 to 10% of cases, codes for a protein that helps LDL particles dock onto those liver receptors. When this protein is defective, LDL particles can’t attach properly, so they stay circulating in the bloodstream. A third gene, responsible for fewer than 3% of cases, normally helps regulate how many LDL receptors the liver keeps active. Mutations here cause the liver to break down its own receptors too aggressively, leaving fewer available to clear cholesterol.
There is also a rare recessive form caused by a fourth gene. In this version, both parents must carry a copy of the mutation (often without knowing it), and each child has a 25% chance of being affected. More than 20 mutations in this gene have been identified, all of which prevent cells from producing a functional version of the protein needed to internalize LDL particles.
Heterozygous vs. Homozygous FH
The severity of FH depends on whether you inherited one or two copies of the faulty gene. The vast majority of people with FH are heterozygous, meaning they have one normal copy and one altered copy. Heterozygous FH typically produces LDL cholesterol levels roughly double the normal range. Without treatment, these individuals may experience their first cardiovascular event as early as their thirties.
Homozygous FH occurs when both parents have the condition and each passes along their mutated gene. This is rare, but the consequences are severe. LDL levels often exceed 500 mg/dL, more than four times what’s considered healthy, and cardiovascular complications can begin in childhood, sometimes within the first decade of life. Anyone with fasting LDL above 370 mg/dL should be evaluated by a specialist for possible homozygous FH.
How It Affects Your Children
If you have heterozygous FH, each of your children has a 1-in-2 chance of inheriting it. If both you and your partner have it, each child faces a 1-in-4 chance of inheriting two copies (homozygous FH), a 1-in-2 chance of inheriting one copy, and a 1-in-4 chance of inheriting none. Because FH is so common, two carriers having children together is not as unlikely as it might sound.
The European Atherosclerosis Society recommends cholesterol screening for children with a family history of FH by age 5. Japanese guidelines suggest testing by age 10 at the latest, with earlier testing if homozygous FH is suspected. In children, an LDL level of 160 mg/dL or higher combined with a parent who has premature heart disease or high LDL is considered diagnostic. Even levels above 130 mg/dL warrant monitoring if a parent carries a confirmed FH mutation.
Cascade Screening: Testing the Family Tree
Because FH follows such a clear inheritance pattern, diagnosing one person in a family opens a direct path to finding others. This process, called cascade screening, starts with first-degree relatives: parents, siblings, and children of the diagnosed person. If an affected parent is identified, screening expands to that parent’s side of the family, including their siblings and those siblings’ children.
Each newly identified case becomes a starting point for further screening. A single diagnosis can ultimately uncover dozens of affected family members across multiple generations. This matters because FH is dramatically underdiagnosed. Large studies in the U.S. and Europe have converged on a prevalence of roughly 0.4%, yet most people with FH don’t know they have it. Many are told they simply have “high cholesterol” without recognizing the genetic component.
Why the Genetic Distinction Matters
Ordinary high cholesterol responds well to diet changes and standard medication. FH-related high cholesterol is present from birth, progresses throughout life, and is largely independent of lifestyle. The underlying problem is structural: your liver cells lack enough functional receptors to pull LDL from the blood at a normal rate. This also means LDL precursor particles accumulate and get converted into additional LDL, so the condition actually increases LDL production while simultaneously decreasing LDL clearance.
Knowing that your high cholesterol is genetic changes the treatment approach, the urgency of intervention, and the importance of screening your relatives. A confirmed genetic mutation carries the highest diagnostic weight in clinical scoring systems. On the Dutch Lipid Clinic Network scale, widely used to diagnose FH, a confirmed mutation in one of the three major genes scores 8 points on its own, enough to classify the diagnosis as “definite.” Family history of early heart disease in a close relative adds 1 to 2 points. The genetic finding, in other words, is the single most powerful piece of diagnostic evidence.