Overview
RIDDLE syndrome is an extremely rare genetic condition that affects the immune system and the way the body repairs damaged DNA. The name RIDDLE stands for Radiosensitivity, Immunodeficiency, Dysmorphic features, and Learning difficulties — which describes the main problems the condition causes. It is caused by changes (mutations) in a gene called RNF168, which plays an important role in fixing breaks in DNA strands. When this gene does not work properly, the body struggles to repair DNA damage, which leads to a range of serious health problems. People with RIDDLE syndrome typically have a weakened immune system, making them more vulnerable to infections. They are also unusually sensitive to radiation, which is important to know before any medical imaging or treatment. Many affected individuals have learning difficulties and may show certain physical features that doctors can recognize. Growth problems and neurological issues have also been reported. Because RIDDLE syndrome is so rare — with only a handful of cases described in medical literature — treatment is largely focused on managing symptoms rather than curing the underlying cause. Care usually involves a team of specialists working together to address infections, support learning and development, and monitor for complications. There is currently no approved cure or disease-modifying therapy.
Also known as:
Key symptoms:
Weakened immune system leading to frequent or severe infectionsUnusual sensitivity to radiation (radiosensitivity)Learning difficulties and intellectual disabilityDistinctive facial features (dysmorphic features)Short stature or growth delaysProblems with balance and coordinationNeurological difficultiesDelayed development in childhoodIncreased risk of DNA damage accumulation
Clinical phenotype terms (43)— hover any for plain English
Autosomal recessive
Passed on when both parents carry the same gene change; often skips generations
Childhood
Begins in childhood, roughly ages 1 to 12
Treatments
No FDA-approved treatments are currently listed for RIDDLE syndrome.
View clinical trials →Clinical Trials
View all trials with filters →No actively recruiting trials found for RIDDLE syndrome at this time.
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Specialists
View all specialists →No specialists are currently listed for RIDDLE syndrome.
Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Travel Grants
No travel grants are currently matched to RIDDLE syndrome.
Community
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Caregiver Resources
NORD Caregiver Resources
Support, advocacy, and financial assistance for caregivers of rare disease patients.
Mental Health Support
Rare disease caregiving can be isolating. Connect with counseling and peer support.
Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
Social Security Disability
Learn how rare disease patients may qualify for SSDI/SSI benefits.
Questions for your doctor
Bring these to your next appointment
- Q1.What infections should I watch out for most, and when should I go to the emergency room?,How should we handle any future medical procedures that involve radiation, such as X-rays or CT scans?,Should my child receive immunoglobulin replacement therapy, and how would that work?,What educational support or therapies do you recommend for the learning difficulties?,Are there any clinical trials or research studies we could participate in?,Should other family members be tested for the RNF168 gene mutation?,Which specialists should be part of our care team, and how often should we see each one?
Common questions about RIDDLE syndrome
What is RIDDLE syndrome?
RIDDLE syndrome is an extremely rare genetic condition that affects the immune system and the way the body repairs damaged DNA. The name RIDDLE stands for Radiosensitivity, Immunodeficiency, Dysmorphic features, and Learning difficulties — which describes the main problems the condition causes. It is caused by changes (mutations) in a gene called RNF168, which plays an important role in fixing breaks in DNA strands. When this gene does not work properly, the body struggles to repair DNA damage, which leads to a range of serious health problems. People with RIDDLE syndrome typically have a wea
How is RIDDLE syndrome inherited?
RIDDLE syndrome follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does RIDDLE syndrome typically begin?
Typical onset of RIDDLE syndrome is childhood. Age of onset can vary across affected individuals.