THOC2-related disorders are congenital genetic conditions, caused by a variety of gene changes or ‘pathogenic variants’ in the THOC2 gene on the X chromosome.
Main clinical features
The core clinical feature is intellectual disability/developmental delay, which can range in severity from mild to profound. Additional neurological features including infantile hypotonia, ataxia or disordered gait, seizure disorder or tremor are present in some affected individuals.
The prevalence of THOC2-related disorder cannot be ascertained accurately due to the limited number of affected individuals identified to date. Since the condition was first described in 2016, thirty seven individuals have been reported in the literature with THOC2-related disorder. We are learning more as additional individuals are diagnosed.
The THOC2 gene is located on the X chromosome. THOC2-related disorder can therefore be inherited in a family by X-linked inheritance. There are also 3 affected males with de novo [‘new’] genetic changes and one affected female with a ‘de novo’ [new] genetic change reported in the literature.
In families with an inherited THOC2 variant, heterozygous carrier females of a confirmed pathogenic THOC2 variant are typically healthy with normal intelligence and, when tested, have skewed X chromosomal inactivation. However, it is possible that, as in other X-linked conditions some female carriers of an inherited THOC2-related disorder may also have clinical features. This will need to be carefully assessed as more families are reported.