Tatton Brown Rahman Syndrome Community
Cycle 2
Tatton Brown Rahman Syndrome (TBRS) is a rare genetic disease caused by pathogenic variants in the DNMT3A gene (also called DNMT3A Overgrowth Syndrome). Individuals with TBRS have overgrowth—typically, tall stature, increased weight, and large head circumference (also known as macrocephaly)—mild to severe intellectual disability, and subtle but distinctive facial characteristics. The syndrome varies considerably in its severity.
Last updated 04/30/2025
Clinical
Disease Class
Genetic diseases
Neurological diseases
Body Systems
Cardiovascular / Circulatory
Digestive
Endocrine
Hematopoietic / Lymphatic / Immune
Integumentary / Exocrine
Metabolic
Muscular / Skeletal
Nervous / Sensory
Renal / Urinary / Excretory
Reproductive
Respiratory
Organs
Adrenal glands
Arteries
Blood
Bone marrow
Bones
Brain
Connective tissue / joints
Ears
Esophagus
Eyes
Hair
Heart
Intestines
Kidneys
Lungs
Mouth / teeth
Muscles
Nails
Nerves
Ovaries
Penis
Skin
Spleen
Stomach
Testes
Known Genetic Link
Yes, one or more genes directly cause the condition
causative_genes
DNMT3A
contributory_genes
None specified / unknown
Type of Inheritance
Autosomal dominant
De novo
Newborn Screening
No
Disease Mechanism(s)
Other
Pathogenic mutation
Age of Onset
Prebirth
Average Age at Diagnosis
Early childhood (age 1+-5)
Middle childhood (6-11)
Life Expectancy
Adulthood (age 18-64)
Affected Sex(es)
Female
Male
National Prevalence
101-1000
Global Prevalence
101-1000
National Incidence
51-100
Global Incidence
51-100
Populations and/or ancestry with higher prevalence
Diagnosis more common in US, Canada, and Europe. Higher identification in white population.
Symptoms / Phenotypes
abnormal heart morphology
abnormality of the dentition
autism
autistic behavior
behavioral changes
cancer / carcinoma / tumor / malignancy, unspecified
cancer, leukemia
cardiac abnormalities
cryptorchidism
developmental delay
distinctive facial features
functional motor deficit
gastrointestinal disorders
hyperlaxity / joint laxity
hypotonia
intellectual disability
macrocephaly
seizures / epilepsy
sleep disorders
tall stature
weight gain
Biomarkers
Diagnostic
· genetic test/DNMT3A variant
Existing Therapies
None
Organizational & Research
Cell Lines
iPSCs
Cell Lines, Institution
Van Andel Institute
Cell Lines, Involvement
Consulted
Designed
Funded
Own
Cell Lines, share
Some of our cell lines are freely available
Disease Model
Mouse
Disease Model, Involvement
Consulted
Funded
Disease Model, share
Some of our disease models are freely available
Clinical Trial Role
Not involved
Biobank, Institution
COMBINEDBrain
Van Andel Institute
Biobank, Involvement
Funded
Own
Center of Excellence, Institution
None
Registry
Yes, we have a registry that we created
Data Collected, Registry
Clinical data
Electronic health records/electronic medical records
Genetic data
Imaging data
Longitudinal natural history data
Medication usage
Patient contact info
Patient-reported data
Data Entered by, Registry
Patients
Platform, Registry
IAMRARE
Natural History Study
Yes, we have a natural history study that we created
Data Collected, Natural History Study
Electronic health records/electronic medical records
Genetic data
Imaging data
Medication usage
Patient-reported outcomes
Prospective data
Platform, Natural History Study
IAMRARE
FDA Patient Listening Session
No
FDA Patient-Focused Drug Development (PFDD) Program
No
ICD Codes
No, we do not have any ICD codes
Diagnostic Guidelines
In the process of creating diagnostic guidance for our website
Science Advisory Board Policies
No policies
Research Network Policies
Has CRN but no policies
Research Roadmap
Yes we have a Research Roadmap, and will share policies
International Chapters
Europe
International Partners
Europe