Clinical Characteristics

This is a summary of the clinical characteristics of affected male individuals with a confirmed THOC2-related condition:

  1. Global developmental delay/ Intellectual disability: All affected males have some degree of intellectual disability. This can range from mild to severe, with approximately 20% reported to have mild ID, and 80% moderate-severe. Delays in the acquisition of speech and language is particularly noted. Some individuals are able to talk fluently in sentences, whereas for others communication is limited to a few words, or to alternative communication methods such as picture exchange.
  2. Disorders of tone and movement: Low tone in infancy is commonly reported (45%), often with associated delays in the attainment of gross motor milestones. Other neurological features that have been reported include tremor (35%), a disordered gait (e.g. broad based/ ataxic gait or toe walking 24%), and hyperkinesia/ hyperactivity (30%).
  3.  Behavioural/ mental health disorders: Behavioural disorders are reported in 45%: this can range from auto and hetero-aggressive behaviours to features on the autistic spectrum. Some older individuals have been diagnosed with anxiety and/or depression from adolescence/early adulthood.
  4.  Seizure disorder: seizure disorders have been reported in a minority of individuals with THOC2-related disorder, and range from well controlled epilepsy to more severe seizure disorders starring in early childhood.
  5.  Changes in neuroimaging: not all in individuals with THOC2-related disorder have had a brain MRI or CT, but in those who have this was reported as normal in 45% and with variable abnormalities in 55% – including thinning of the corpus callosum, delayed myelination/ white matter changes, ventriculomegaly and cortical gyral abnormalities.
  6.  Disorder of growth: disorders in growth are commonly reported, with 50% having significant short stature (below the 3rd percentile) and 40% having microcephaly. One individual is known to have been treated with growth hormone supplementation. Although low or normal body weight is typical in childhood, several older individuals have developed truncal obesity and have high BMI.
  7.  Other physical conditions: the majority of individuals with THOC2-related disorder are reported to be physically healthy. A minority have additional differences including looser or more flexible joints, flat feet (‘pes planus’), and differences in male external genitalia including smaller penis size and undescended testes (cryptorchidism). Although some individuals may have distinctive facial features, including a tall broad forehead, most affected individuals resemble their unaffected family members.

To date only one female is reported to be affected by a THOC2-related disorder. Her features included severe intellectual disability and childhood onset seizure disorder. The majority of females in families who have been found to carry a THOC2 gene change have been healthy with normal intelligence.