TBR1-related disorder is caused by changes (also known as variants or mutations) in the TBR1 gene.
Patients with TBR1-related disorder have neuro-developmental difficulties. They present with mild to severe developmental delay (DD) and ID. About 75% of the affected individuals have autistic traits. Aside from DD/ID and autistic traits, most of the other TBR1-associated features are either nonspecific or infrequent.
Most patients have:
• Developmental delay
• Mild to severe ID
• Autistic traits
• Behavior disorders (mainly attention deficit and aggressive behavior)
• Hypotonia (low muscle tone/floppiness) and fine motor delay
Other possible features include:
• Facial particularities
• Skeletal features
• Intra-uterine growth retardation
• Abnormal movements
• Seizures / abnormal EEG (electroencephalogram) without seizure
• Abnormal brain MRI (Magnetic resonance imaging) findings
• Constipation
• Feeding difficulties
• Small head circumference (microcephaly)
TBR1-related disorder is extremely rare, with about 40 individuals being identified worldwide (2020), although many patients currently remain undiagnosed.
The possibility of having another child affected by a rare gene disorder depends on the genetic code of the parents. In most families, this genetic change has happened for the first time in the child with TBR1-related disorder. This is called ‘de novo’. When the parents are unaffected, the risk of having another child with the same condition are very low (<1%). This risk is linked to the possibility of a germline mosaicism meaning the presence of a TBR1 mutation in a percentage of female egg cells or male sperm. In any case, a meeting with a geneticist and genetic counselor is recommended for informed decision making about future pregnancies.
TBR1-related disorder is an autosomal dominant disorder, meaning that boys and girls could be affected. A person with an autosomal dominant disorder has a 50% chance of having an affected child with one mutated gene and a 50% chance of having an unaffected child.