Clinical features
All reported patients with different PPP3CA pathogenic variants have global developmental delay and cognitive dysfunction. The other common findings are epilepsy (81%), structural brain abnormalities (57%), hypotonia (62%), and autistic features (55%). Patients with GoF variants do not have epilepsy but have congenital abnormalities.
Prevalence
PPP3CA-associated neurodevelopmental disorders are rare and there are less than 30 patients have been reported in the literature to date.
Genetic counselling
Heterozygous pathogenic or likely variants in PPP3CA cause autosomal dominant genetic diseases. To date all reported cases result from a de novo variant. Thus, the affected individuals represent sporadic cases, i.e., a single occurrence in a family. The recurrence risk for future pregnancies is considered low and about 1%. Prenatal testing is feasible and offered to the interested families through prenatal genetic clinics.
PPP3CA