Physical Development:
Patients with TBR1-related disorder learn to walk alone, but this may be slightly to severely delayed. Hypotonia and/or joint laxity may play a role in delays.
• Learning
Children with TBR1-related disorder typically have learning difficulties and are often given a diagnosis of intellectual disability (ID). They typically need extra help in school. Although most go to a mainstream primary school, the extra demands of mainstream secondary school may prove too challenging, and children may transfer to special schooling or remain in mainstream schools with Educational Health Care Plans (EHCP).
• Behavior
Children with rare chromosomal and genetic disorders often have behavioral, social and/or communication difficulties and vulnerability in these areas means that children should be monitored and families offered early support. Behavioral disorders are frequent in TBR1-related disorders notably autistic traits, attention deficit, anxiety and aggressive behavior. Children are also described by their parents as being happy and loving.
• Speech and language
All children with TBR1-related disorder identified so far, have moderate to severe speech delay. Some children are non-verbal. Hearing and visual impairments must be detected and corrected as early as possible to limit delays.
• Growth is generally normal. Some children have been reported with a short stature but a few children are known to be tall.
Neurological features:
• Low muscle tone (hypotonia) and fine motor delays are frequent in early childhood and contribute to developmental delays. Gait disorders (not walking as expected) and abnormal movements such as uncontrolled muscle spasms (dystonia), involuntary rapid and jerky body movements (chorea), or involuntary, rhythmic muscle contractions (tremors) have been observed in some children.
• Changes to brain structure that have been observed on MRI include abnormal cortex, abnormal hippocampi and a thin/absent anterior commissure. These changes are related to the dysfunction of the TBR1 protein and explain the cognitive difficulties.
• Seizures
A few children with TBR1-related disorder have experienced seizures, including absence (sudden lapse in consciousness) tonic-clonic (when muscles stiffen (tonic) and arms/legs jerk (clonic), and generalized seizures (impaired consciousness with movement of arms and legs). Children respond to typical drug treatment for epilepsy. Some children have an abnormal EEG without clinical seizures.
• Facial features
Just over half of children with TBR1–related disorder identified so far have minor and non-specific facial features including high or large forehead, wide nasal bridge, long groove between the nose and upper lip (philtrum), protruding jaw (prognathism), and wide mouth.
• Skeletal features
Skeletal features concern about half of affected children. They are minor and variable, including ‘loose’ joints (joint laxity, flat feet (pes planus), curvature of the spine (scoliosis) and/or joint deformation.
Other less common medical conditions
• Constipation can be mild to severe and concerns about 25% of affected children.
• Feeding difficulties have been identified in about 15% of children described in the medical literature, potentially leading to severe complications or surgeries such as Nissen fundoplication [a surgical procedure to treat gastroesophageal reflux disease (GERD)]
• Strabismus (misaligned eye) is the only visual disorder reported so far and affects a few children.
TBR1