What Is TBRS?
Tatton Brown Rahman Syndrome (TBRS) is a complex and rare disorder characterized by overgrowth, varying degrees of intellectual disability, and characteristic facial features that become more apparent with age. TBRS can affect many systems in the body. Individuals may present with autism, joint hypermobility, low muscle tone, kyphoscoliosis, seizures, behavioral and mental health disorders, heart defects, obesity, hearing and vision concerns, sleep apnea, blood disorders, and an increased risk for certain cancers, especially leukemia.
TBRS creates many challenges for families, but it has also created a supportive, loving community of people who recognize the special talents and beautiful personalities of those living with TBRS.
Overgrowth
Most individuals are taller than average and have larger head size (macrocephaly).
Intellectual Disability
Ranges from mild to severe; often requires individualized learning support.
Facial Features
Often include thick eyebrows, narrow eyes, round face, large front teeth, and broad forehead. These become more noticeable with age.
Other Common Health Concerns
Joint Hypermobility
Loose joints may lead to pain or injury.
Low Muscle Tone (Hypotonia)
Can affect posture, balance, and coordination
Kyphoscoliosis
Curvature of the spine in approximately one-third of patients
Seizures
About 47% experience seizures, with or without fever.
Heart Conditions
Roughly 49% have structural issues like holes in the heart.
Neuropsychiatric Conditions
May include autism, ADHD, and anxiety
Early puberty
Development progresses faster for some patients.
Sleep conditions
Includes sleep apnea and other sleep-related disorders
Blood disorders
Data suggest changes in DNMT3A may be linked with increased risk of leukemia and other blood conditions.
Additional concerns include increased risk of developing cancer, hearing and vision concerns, and dental issues.
The Genetics Behind TBRS
Most people with TBRS have a spontaneous mutation in DNMT3A, meaning they did not inherit it from their parents.
The faulty gene disrupts normal development by altering DNA methylation, an important function in cells that determines which genes are activated.
There’s a 50% chance of passing the condition to children if a parent has TBRS.
TBRS and Cancer:
What We Know
Some TBRS mutations overlap with those found in leukemia, particularly acute myeloid leukemia (AML). While the overall cancer risk for TBRS patients is still considered low, certain DNMT3A mutations may increase this risk, especially mutations at Arg882. If someone with TBRS shows symptoms such as unexplained bruising, fatigue, or recurrent infections, speak with your doctor.
The TBRS Community and our research partners are working to better understand the links between TBRS and cancer.
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