WHAT IS CTNNB1 SYNDROME?
CTNNB1 Syndrome is a severe neurodevelopmental disorder caused by disruption of chromosome 3p22.1 of the CTNNB1 gene (Verhoeven et al. 2020). It is a recently discovered condition associated with developmental delay, intellectual disability and speech delay. The first cases of CTNNB1 syndrome were reported in 2012, so there are probably many more undiagnosed cases living with this disease. Recent studies report that the CTNNB1 gene is the most common cause of misdiagnosed cerebral palsy cases (Jin et al. 2020; Moreno-De-Luca et al. 2021).
CTNNB1 Syndrome affects 1 out of 50.000 children worldwide (Chung for ACCT, 2019). It is inherited in an autosomal dominant pattern, meaning only one copy of a gene variant is needed in order to express an observable phenotype. CTNNB1 syndrome occurs when one of the two copies of the CTNNB1 gene has lost its normal function. It usually occurs de novo, meaning that it was not inherited from parents.
CTNNB1 is important in the development and maturation of the brain and de novo mutations cause learning and memory problems. This is why CTNNB1 syndrome is primarily associated with developmental delay/intellectual disability.
De novo loss-of-function mutations in CTNNB1 gene are causative for Neurodevelopmental Disorder with Spastic Displegia and Visual Defects (NEDSDV) and Familial Exudative Vitreoretinopathy (FEVR). FEVR is a dominant disorder characterized by the incomplete development of the retinal vasculature. NEDSDV is a neurodevelopmental disorder characterized by global developmental delay, impaired intelectual development with absent or very limited speech, craniofacial anomalies features with microencephaly, axial hypotonia, and spasticity (Verhoever et al. 2020; Kuechler et al. 2015).