PUM1-related disorders are caused by a variety of mutations or pathogenic variants in the PUM1 gene on chromosome 1. Currently two distinct PUM1-related disorders are recognised: the congenital Pumilio1-associated developmental disability, ataxia, and seizure (PADDAS) syndrome and the late-onset Pumilio1-related cerebellar ataxia (PRCA).
Main clinical features: The core clinical feature of PADDAS is intellectual disability/developmental delay, which can range in severity. Seizures are commonly reported, as is gait disturbance/ataxia. PRCA, when penetrant, is characterised by pure cerebellar ataxia with onset in mid-life or later.
Prevalence: The prevalence of PUM1-related disorder cannot yet be ascertained because only a limited number of affected individuals have been identified to date. Since the condition was first described in 2017, more individuals (in addition to the original 20) with a PUM1-related disorder have been reported in the literature. We are learning more as additional individuals are diagnosed.
Inheritance: The PUM1 gene is located on chromosome 1. Individuals with PADDAS typically have the condition due to a de novo genetic change. PRCA has only been reported in one family to date, where the mutation was inherited in an autosomal dominant manner with incomplete penetrance.