Neurodevelopmental disorders related to protein phosphatase 2 catalytic subunit alpha (PPP2CA) are currently recognized as Houge–Janssens syndrome 3 (OMIM: 618354), an autosomal dominant disorder characterized by developmental delay, intellectual disability, autism spectrum disorder, seizures, brain abnormalities, and hypotonia. Here, we report a patient with a PPP2CA variant. Trio-based whole-exome sequencing was performed on the patient and her parents, and a novel de novo heterozygous variant PPP2CA (NM_002715: c.218G > A, p.Gly73Asp) was identified, resulting in an amino acid substitution within the catalytic subunit. Clinically, the patient presented with epilepsy, hypotonia, attention-deficit/hyperactivity disorder, and intact intellectual functioning; there were no structural brain abnormalities. PPP2CA variants are rare, and the variant identified in this study has not been previously reported in the literature or public databases. Our findings support the pathogenicity of this variant and further expand the pathogenic variant spectrum of the PPP2CA gene. Furthermore, the observed genotype–phenotype correlation provides valuable information for prognosis and genetic counseling.