PLCG2-associated antibody deficiency and immune dysregulation

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ORPHA:300359OMIM:614468L50.2
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Overview

PLCG2-associated antibody deficiency and immune dysregulation, often called PLAID, is a rare genetic condition that affects the immune system. It is caused by changes (mutations) in the PLCG2 gene, which plays an important role in how immune cells communicate and respond to threats. People with PLAID typically experience cold-induced hives (urticaria), meaning their skin breaks out in itchy welts when exposed to cold air, cold water, or even cool temperatures. This is one of the most recognizable features of the disease. Beyond the skin symptoms, PLAID causes problems with the immune system's ability to produce antibodies, which are proteins that help fight infections. This antibody deficiency means people with PLAID are more prone to frequent or severe infections, particularly of the sinuses, ears, and lungs. Some patients also develop autoimmune problems, where the immune system mistakenly attacks the body's own tissues. Allergic symptoms and inflammation can also occur. A related but distinct condition called APLAID (autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation) involves different mutations in the same gene but tends to cause more inflammatory symptoms, including skin rashes, eye inflammation, joint pain, and digestive problems, with less prominent cold-induced hives. Treatment for PLAID and APLAID is mainly supportive, focusing on managing symptoms, preventing infections with antibiotics or immunoglobulin replacement therapy, and avoiding cold exposure. There is currently no cure, and management requires a team of specialists.

Also known as:

Key symptoms:

Hives or welts triggered by cold exposure (cold urticaria)Frequent sinus infectionsFrequent ear infectionsFrequent lung infections or pneumoniaLow levels of antibodies in the bloodSkin rashes or blisteringAllergic-type reactionsAutoimmune symptoms such as joint pain or skin changesEye inflammation (in APLAID variant)Digestive problems such as diarrhea or abdominal painGranuloma formation (small areas of inflammation in tissues)Swelling of the skinFatigue and low energyPoor wound healing

Inheritance

Autosomal dominant

Passed on from just one parent; each child has about a 50% chance of inheriting it

Age of Onset

Childhood

Begins in childhood, roughly ages 1 to 12

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for PLCG2-associated antibody deficiency and immune dysregulation.

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No actively recruiting trials found for PLCG2-associated antibody deficiency and immune dysregulation at this time.

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No specialists are currently listed for PLCG2-associated antibody deficiency and immune dysregulation.

View NORD Rare Disease Centers ↗Undiagnosed Disease Network ↗

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to PLCG2-associated antibody deficiency and immune dysregulation.

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Community

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Caregiver Resources

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Questions for your doctor

Bring these to your next appointment

  • Q1.How severe is my (or my child's) antibody deficiency, and will immunoglobulin replacement therapy be needed?,What specific precautions should we take to avoid cold-triggered symptoms?,Are there signs of autoimmune problems that need to be monitored?,How often should blood work and immune function tests be repeated?,Should other family members be tested for the PLCG2 mutation?,What should we do in case of a severe allergic reaction or anaphylaxis?,Are there any clinical trials or new treatments being studied for this condition?

Common questions about PLCG2-associated antibody deficiency and immune dysregulation

What is PLCG2-associated antibody deficiency and immune dysregulation?

PLCG2-associated antibody deficiency and immune dysregulation, often called PLAID, is a rare genetic condition that affects the immune system. It is caused by changes (mutations) in the PLCG2 gene, which plays an important role in how immune cells communicate and respond to threats. People with PLAID typically experience cold-induced hives (urticaria), meaning their skin breaks out in itchy welts when exposed to cold air, cold water, or even cool temperatures. This is one of the most recognizable features of the disease. Beyond the skin symptoms, PLAID causes problems with the immune system's

How is PLCG2-associated antibody deficiency and immune dysregulation inherited?

PLCG2-associated antibody deficiency and immune dysregulation follows a autosomal dominant inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does PLCG2-associated antibody deficiency and immune dysregulation typically begin?

Typical onset of PLCG2-associated antibody deficiency and immune dysregulation is childhood. Age of onset can vary across affected individuals.