Signs and Symptoms of V122I Hereditary ATTR Amyloidosis

Introduction

Hereditary ATTR amyloidosis is a genetic condition that can affect different parts of the body. The V122I gene variant, which occurs more often in people with West African ancestry, is most commonly linked to heart disease known as ATTR cardiomyopathy.

Symptoms may develop slowly and can look different from person to person. Some people who carry the gene may develop symptoms, while others may never experience noticeable disease.

Learning the possible signs can help families recognize patterns in their family health history and start informed conversations with healthcare professionals.

What are the early signs and symptoms of hereditary ATTR amyloidosis?

Early signs and symptoms of hereditary ATTR (hATTR) amyloidosis can be subtle and may develop slowly over time. They often affect the nerves, heart, digestive system, and musculoskeletal system.

Possible early signs may include:

  • Numbness or tingling in the hands or feet

  • Bilateral carpal tunnel syndrome

  • Lumbar spinal stenosis or back issues

  • Tendon injuries, including distal biceps tendon rupture

  • Shortness of breath or reduced stamina

  • Swelling in the legs or feet

  • Irregular heartbeat

  • Digestive changes such as constipation, diarrhea, or feeling full quickly

  • Dizziness when standing

  • Unexplained fatigue or weight loss

Because these symptoms can appear unrelated or develop gradually, hereditary amyloidosis is often underrecognized or diagnosed later than expected.

This includes individuals with the V122I (Val122Ile) gene variant, which is more commonly seen in people of African descent and may increase the risk of developing ATTR amyloidosis.

Continue below to see how these symptoms show up in the body and what they may mean.

V122I hereditary ATTR amyloidosis symptoms including heart, nerve, digestive, and musculoskeletal signs

Signs and Symptoms Explained

A realistic model of a human heart with detailed veins and arteries, placed on a plain gray surface.

Heart

Heart involvement is one of the most common features of V122I hereditary ATTR amyloidosis.

Possible signs may include:

• Shortness of breath
• Swelling in the legs or ankles
• Irregular heartbeat
• Extreme fatigue

These symptoms can sometimes be mistaken for other heart conditions.

Image of man being surrounded by tornado like swirl

Body Regulation Symptoms

Amyloidosis can sometimes affect the autonomic nervous system, which helps regulate body functions.

Possible symptoms include:

• Dizziness when standing
• Bladder or bowel problems
• Changes in sexual function

Nerve and Brain

Nerve Symptoms

Some individuals may experience symptoms related to nerve involvement.

Possible signs include:

• Tingling or numbness in the hands or feet
• Loss of feeling in the feet

These symptoms may develop slowly and may overlap with other nerve conditions.

image of spine and joints

Muscle and Joint Symptoms

Certain musculoskeletal conditions may appear years before heart symptoms are diagnosed.

Possible signs include:

• Bilateral carpal tunnel syndrome
• Carpal tunnel symptoms that return after surgery
• Lumbar spinal stenosis
• Distal biceps tendon rupture

These conditions are common but may provide important clues when they occur together.

image of digestive track

Digestive Symptoms

Some individuals may experience digestive changes.

Possible symptoms include:

• Constipation or diarrhea
• Feeling full quickly when eating
• Nausea
• Unplanned weight loss.

Symptoms Can Vary

Not everyone with the V122I gene variant develops symptoms. Even within the same family, symptoms and age of onset may look different.

Researchers are still working to understand why the condition affects individuals differently.

Final Call to Action

Know Your Roots. Know Your Risks.

If you recognize symptoms that raise concerns, consider speaking with a healthcare professional. Having one or even several of these symptoms does not automatically mean someone has hereditary ATTR amyloidosis. A healthcare provider can help evaluate what you are experiencing and rule out other possible causes.

You can also download this symptoms guide and explore additional educational tools in the #hATTRNextGen Resource Hub.