Main clinical features include:
• ID: mild in 8%, moderate in 26%, severe in 61% (NA 5%)
• Moderate to severe speech delay. Some individuals are non-verbal.
• Autistic traits expressed as social and/or communication difficulties, echolalia, rituals, stereotypic behavior (76%)
• Behavior disorders: attention deficit/ hyperactivity disorder, anxiety and aggressive behavior (85%)
• Neurological features: hypotonia, fine motor delays, abnormal gait, abnormal movements such as dystonia, chorea, or tremors have been observed in some individuals.
• Seizures in some individuals with TBR1-related disorder including absence, tonic-clonic, and generalized seizures. Some individuals have an abnormal EEG without clinical seizures.
• Cerebral MRI abnormalities in some individuals: dysplastic hippocampi and hypoplasia or agenesia of the anterior commissure could be distinctive features, abnormal cortex (pachygyria, thick frontal cortex), thin corpus callosum with large lateral ventricles, myelinization delay, cyst of the cavum vergae
• Cranio-facial dysmorphism: Just over half of individuals with TBR1–related disorder identified so far have minor and non-specific cranio-facial dysmorphism such as a high or large forehead, wide nasal bridge, long philtrum, prognathism, and wide mouth.
• Skeletal anomalies may be present in about half of affected individuals. They are minor and variable, including joint laxity, pes planus, scoliosis and/or joint deformation.
• Growth is generally normal. Some individuals have been reported to have short stature but a few children are known to be tall.
• Constipation can be mild to severe and is present in about 25% of affected children.
• Feeding difficulties have been identified in about 15% of individuals, potentially leading to severe complications or surgeries such as Nissen fundoplication
• Strabismus is the only visual disorder reported to date, affecting few children.
*Percentages are based on the patient population known in the summer of 2021