Yes, familial hypercholesterolemia (FH) is autosomal dominant in the vast majority of cases. That means you only need to inherit one copy of the faulty gene, from one parent, to develop the condition. If a parent has FH, each of their children has a 50% chance of inheriting it.
There is a rare exception: mutations in a gene called LDLRAP1 cause an autosomal recessive form, which requires two copies of the faulty gene (one from each parent). But this form accounts for a small fraction of all FH cases.
What Autosomal Dominant Means in Practice
Autosomal dominant inheritance is straightforward. The gene sits on a non-sex chromosome, so it affects males and females equally. One altered copy is enough to raise LDL cholesterol significantly from birth. You don’t need to inherit the mutation from both parents, and you can’t be a silent carrier who passes it on without being affected yourself. If you have the mutation, your cholesterol is elevated.
This pattern also means FH tends to run visibly through families. You’ll often see a line of parents, grandparents, and siblings with high cholesterol or early heart disease. About 3 in every 1,000 people carry a single copy of an FH mutation, making it one of the most common serious genetic disorders.
The Genes Involved
Three genes account for the vast majority of genetically confirmed FH cases. The most commonly affected is the LDL receptor gene, which provides instructions for building the protein that pulls LDL (“bad”) cholesterol out of the bloodstream and into liver cells for disposal. When this gene is mutated, the liver can’t clear LDL efficiently, so it accumulates in the blood.
The second gene codes for a protein on the surface of LDL particles that helps them dock with the liver’s receptors. When this protein is altered, LDL particles can’t attach properly, and they stay circulating. The third gene controls a protein that normally breaks down LDL receptors. Certain mutations cause this protein to become overactive, destroying too many receptors and leaving fewer available to clear cholesterol. Over 2,900 different variants across these three genes have been linked to FH, which is one reason the condition varies in severity from person to person.
One Copy vs. Two Copies
Because FH is autosomal dominant, inheriting one mutated copy (heterozygous FH) is enough to cause disease. But in rare cases, a person inherits mutations from both parents, resulting in homozygous FH, a far more severe condition.
Heterozygous FH is the common form. LDL cholesterol is significantly elevated from birth, and without treatment, heart disease can develop decades earlier than expected. Treatment with cholesterol-lowering medications is typically recommended starting between ages 8 and 10.
Homozygous FH is rare and much more dangerous. LDL levels reach extreme highs, and premature coronary artery disease has been documented as early as adolescence. Children with this form can develop fatty deposits under the skin (called xanthomas) during infancy and heart valve problems during childhood, complications that don’t occur in heterozygous FH. Treatment needs to start as soon as possible, and these patients often respond poorly to standard medications because they have little to no functioning LDL receptor activity.
Cardiovascular Risk Without Treatment
Untreated FH carries serious consequences. People with FH who receive no treatment face 20 times the risk of coronary artery disease compared to someone without the condition, according to Cleveland Clinic. This elevated risk begins accumulating in childhood because LDL levels are high from birth, giving cholesterol decades to build up in artery walls.
“Premature” heart disease in this context means heart attacks or strokes before age 55 in men and before age 60 in women. A family history of these events is one of the strongest clinical clues that FH may be present.
How FH Is Diagnosed
Doctors use a combination of family history, physical signs, cholesterol levels, and genetic testing to diagnose FH. One widely used system, the Dutch Lipid Clinic Network criteria, assigns points across these categories. An untreated LDL level above 325 mg/dL scores 8 points on its own. Fatty deposits on tendons (tendon xanthomas) score 6 points. A white or gray ring around the cornea appearing before age 45 scores 4 points. A total above 8 points qualifies as a definite diagnosis.
Genetic testing can confirm the diagnosis definitively. Finding a disease-causing mutation in one of the three main FH genes scores the maximum 8 points in the diagnostic criteria. But not every FH patient has an identifiable mutation with current testing, so a clinical diagnosis based on cholesterol levels and family history remains valid.
Why Cascade Screening Matters
The autosomal dominant inheritance pattern makes FH uniquely suited to a strategy called cascade screening. Once one person in a family is diagnosed, their first-degree relatives (parents, siblings, and children) each have a 50% chance of carrying the same mutation. Screening these relatives with cholesterol testing, genetic testing, or both can identify affected family members before they develop heart disease.
Each newly diagnosed relative then becomes a starting point for testing their own first-degree relatives, expanding outward through the family tree. This cascading approach is highly effective because the inheritance pattern is predictable. If the specific mutation has been identified in the first patient, genetic testing of relatives gives a clear yes-or-no answer. This matters because LDL levels in adults with FH can sometimes overlap with levels seen in people without the condition, meaning cholesterol testing alone misses roughly 20% of affected family members.
One practical barrier in the United States is that privacy rules require the diagnosed patient, not the doctor, to be the one who contacts family members about screening. This places the responsibility on the patient to alert relatives, which can sometimes delay or prevent screening from happening.
Treatment Options
FH is a lifelong condition, but early and consistent treatment dramatically reduces cardiovascular risk. The first-line approach combines statin medications with another cholesterol-lowering drug that blocks cholesterol absorption in the intestine. For many people with heterozygous FH, this combination brings LDL levels down substantially.
When these medications aren’t enough, a newer class of injectable treatments can be added. These drugs work by blocking the protein that destroys LDL receptors on liver cells, essentially helping the liver hold onto more of its cholesterol-clearing machinery. This approach can produce large additional drops in LDL. People with homozygous FH, however, often respond poorly to these treatments because their LDL receptors are severely impaired or absent, and they may require more specialized interventions to manage their cholesterol.