Clinical Characteristics

What are the features of a THOC2-related disorder?

    • Intellectual disability: Individuals affected with a THOC2-related disorder will have some degree of delay in the development of their learning and thinking skills (developmental delay) or intellectual disability. How significantly an individual can be affected can vary significantly between individuals with different gene changes, and even within the same family. The degree of learning difficulties is reported to be in the mild range in about 20% of individuals, and in the moderate-severe range in about 80%. Individuals with THOC2 related disorder are likely to require ongoing supports throughout their lifetime.
    • Speech and Language: All individuals so far described with a THOC2-related disorder have been slower to learn to understand language and speak. Some individuals have not yet been able to learn to speak, and may communicate by alternative methods such as picture exchange systems.
    • Behaviour: Although many individuals have no behavioural disorders, some are reported as being very hyperactive (‘on the go’), have aggressive outbursts or hurt themselves. This can be distressing for family and carers. Support is available to help work out the best way to manage these challenging behaviours. Some individuals have features on the autistic spectrum. A few older individuals with THOC2-related disorder have developed symptoms of anxiety or depression.
    • Seizures: A minority of individuals with THOC2-related disorder have seizures, this may be a mild condition, which is easily controlled with treatment, or more severe condition starting in early childhood.
    • Other neurological symptoms: Many babies with THOC2-related disorder are quite floppy (‘low tone’). Some older children with THOC2-related disorder have additional neurological features (affecting the nerves and/ or muscles) which may include tremor (unsteadiness of the hands) and / or difficulties in balance and walking (for example walking with legs widely spaced apart or up on their toes). Some individuals have had scans of their brains (MRI or CT). Almost have of these have showna normal appearance to their brain, others have shown a range of neuroanatomical changes (e.g. thinning of the white matter parts of the brain, bigger cerebrofluid spaces).
    • Physical features: Most individuals with a THOC2 gene change are healthy and look like unaffected members of their families. Some individuals have relatively slower growth of their heads resulting in smaller sized heads (postnatal microcephaly). Some babies with THOC2 disorder are small at birth. Up to a half of individuals with THOC2-related disorder are short. Most of these features are present by from birth or early childhood, but some features e.g. obesity and mental health difficulties are more likely to develop in older adolescence or adulthood. This is a genetic condition and is not related to environmental exposures or events during pregnancy or in early infant life.


Not all individuals with have these features.