Cardiac amyloidosis can be hereditary, but it isn’t always. One of the two main types, called hereditary transthyretin amyloidosis (hATTR), is caused by a gene mutation passed from parent to child. The other main type, wild-type transthyretin amyloidosis (wATTR), has nothing to do with inherited genes and instead develops as part of the aging process. A third, less common form called AL amyloidosis is also not hereditary. Understanding which type you or a family member has matters enormously, because it determines whether relatives are at risk and what treatment options are available.
The Two Types of Transthyretin Cardiac Amyloidosis
Both hereditary and wild-type cardiac amyloidosis involve the same protein: transthyretin (TTR). This protein normally circulates in your blood as a stable, four-part structure. When that structure breaks apart into individual pieces, those pieces can misfold and clump together into stiff deposits called amyloid fibrils. When those fibrils build up in the heart muscle, the heart becomes thick and rigid, making it harder to pump blood effectively.
In the hereditary form, a mutation in the TTR gene (located on chromosome 18) makes the protein structurally unstable, so it falls apart and misfolds more readily than normal. In the wild-type form, there’s no mutation at all. Instead, the normal TTR protein gradually becomes less stable with age, eventually misfolding on its own. Wild-type cardiac amyloidosis predominantly affects men over 70, while the hereditary form can appear earlier depending on the specific mutation involved.
How the Hereditary Form Is Passed Down
Hereditary transthyretin amyloidosis follows an autosomal dominant inheritance pattern. That means you only need one copy of the mutated gene, from one parent, to be at risk. If a parent carries the mutation, each of their children has a 50% chance of inheriting it.
Carrying the mutation doesn’t guarantee you’ll develop the disease, though. Many people with a TTR mutation live for decades before symptoms appear, and some never develop significant heart problems at all. The age when symptoms start, and whether the heart or the nerves are affected first, varies widely depending on which specific mutation a person carries and other individual factors that aren’t fully understood.
Mutations That Matter Most
More than 130 different TTR mutations have been identified, but a handful account for most cases of hereditary cardiac amyloidosis. The most significant for heart involvement is V122I, a mutation where a single amino acid in the protein is swapped. This variant is carried by 3 to 4% of Black Americans, making it one of the most common disease-causing mutations in any population. It causes a form of cardiac amyloidosis that typically appears later in life, often after age 60, and can be easily mistaken for ordinary heart failure in older adults. Notably, many people with V122I have no known family history of heart disease, which can obscure the hereditary nature of their condition.
Another well-known mutation, Val30Met, is the most common cause of hereditary transthyretin amyloidosis worldwide. It’s especially concentrated in Portugal, Japan, and Brazil. Val30Met more often leads to nerve damage (polyneuropathy) as the primary symptom, though cardiac involvement frequently develops as well. People with the hereditary form generally experience more severe nerve problems than those with wild-type disease, including greater physical disability and more pronounced damage visible on nerve conduction tests. Gastrointestinal symptoms like diarrhea, constipation, and nausea are also more common in the hereditary form.
How Doctors Determine If Your Type Is Hereditary
The diagnostic process for cardiac amyloidosis follows a specific sequence. The first step is always a blood and urine test to screen for abnormal proteins produced by a bone marrow disorder, which would point toward AL amyloidosis rather than the transthyretin type. This step is critical because treatments differ dramatically between AL and ATTR amyloidosis.
If those tests come back negative, the next step is a bone scintigraphy scan, a type of nuclear imaging where a radioactive tracer highlights amyloid deposits in the heart. A strongly positive scan, combined with negative blood and urine screening, can confirm transthyretin cardiac amyloidosis without a biopsy. Performing the scan without the blood and urine screening first is considered a diagnostic error, since over 10% of AL amyloidosis patients can also show positive results on scintigraphy.
Once transthyretin cardiac amyloidosis is confirmed, genetic sequencing of the TTR gene is recommended for every patient. This is the only way to distinguish the hereditary form from wild-type. The distinction has direct implications: it tells you whether your children and siblings might be at risk, and it can influence which treatment approach is most effective.
What This Means for Family Members
If genetic testing reveals a TTR mutation, the question of screening relatives becomes important. Current expert recommendations call for offering genetic testing to at-risk adult family members (age 18 and older) in the context of genetic counseling, where a specialist explains what the results could mean before any blood is drawn. The process typically involves a preliminary clinical exam, a pre-test information session, a waiting period for reflection, the genetic test itself, and a follow-up session to discuss results.
Siblings of a diagnosed patient are generally considered higher priority for testing than children, particularly if those siblings are approaching the age when the diagnosed family member first developed symptoms. The reasoning is straightforward: siblings are closer in age to when the disease might appear, so a positive result has more immediate clinical relevance. Expert guidelines suggest that carriers should begin regular monitoring no later than ten years before the predicted age of symptom onset based on their family’s pattern.
For children who are still decades away from when symptoms would typically appear, the decision to test is more personal. Some people want the certainty so they can plan ahead. Others prefer not to carry that knowledge for years before it becomes actionable. Genetic counseling helps families navigate these decisions without pressure in either direction.
Treatment Differences for Hereditary vs. Wild-Type
Two main treatment strategies exist for transthyretin cardiac amyloidosis. Stabilizers work by reinforcing the four-part TTR structure so it’s less likely to fall apart into amyloid-forming pieces. Silencers take a different approach, blocking the liver from producing TTR protein in the first place, reducing it by 80 to 90%.
Both strategies are used across hereditary and wild-type disease, but there’s a meaningful theoretical advantage for silencers in the hereditary form. Stabilizers hold the mutant protein together more effectively, but some mutant TTR still escapes and breaks down. Silencers, by drastically cutting total TTR production, eliminate most of the problematic protein at the source. Studies in patients with hereditary amyloidosis affecting the nerves have shown that silencers can produce subtle improvements in heart function, raising the possibility that they may be especially well-suited for people with mutations.
Three medications currently represent these two approaches: tafamidis and acoramidis are stabilizers, while vutrisiran is a silencer. Research is ongoing to determine whether one mechanism proves clearly superior to the other for cardiac disease specifically, and whether the answer differs between hereditary and wild-type patients.
When Cardiac Amyloidosis Isn’t Hereditary at All
It’s worth noting that AL amyloidosis, the other major cause of cardiac amyloidosis, is not inherited. It results from a bone marrow disorder where abnormal immune cells produce misfolded protein fragments that deposit in the heart and other organs. AL amyloidosis requires entirely different treatment targeting the abnormal bone marrow cells, which is why the diagnostic algorithm puts bone marrow screening first. If you’ve been told a family member has cardiac amyloidosis but you don’t know which type, the first step is clarifying whether it’s ATTR or AL, since only the ATTR form has a hereditary variant.