TBR1 is located on the long arm of chromosome 2, in the 2q24.2 region. It codes for the T-box brain transcription factor 1. It regulates development of axonal projection and expression of numerous genes involved in autism spectrum disorders (ASD) and intellectual disability (ID).
TBR1-related disorder is a syndromic neurodevelopmental disorder. Almost all of the affected individuals present with mild to severe ID, with 75% of them having autistic traits. To date, only one case without documented ID is known, with only about 40 cases reported worldwide in 2020. It is a recent and likely underdiagnosed condition. Aside from DD/ID and autistic traits, most of the other TBR1-associated features are either nonspecific or infrequent.
These include:
• Intra-uterine growth retardation
• Cranio-facial dysmorphism
• Microcephaly
• Skeletal features
• Abnormal movements
• Seizures / abnormal EEG (electroencephalogram) without seizures
• Abnormal brain MRI ( Magnetic Resonance Imaging) findings
• Feeding difficulties and constipation
The inheritance is autosomal dominant and the disease often occurs de novo.