Clinical and Molecular Spectrum of PPP2R1A-Related Neurodevelopmental Disorders: A Systematic Review
Abstract
Background/Objectives: PPP2R1A encodes the scaffold subunit Aα of protein phosphatase 2A (PP2A). Pathogenic variants cause Houge-Janssens syndrome 2, a rare neurodevelopmental disorder characterized by developmental delay, intellectual disability, epilepsy, and brain malformations. We systematically reviewed published cases to define the clinical spectrum, characterize the mutational landscape, and explore genotype-phenotype correlations. Methods: We conducted systematic searches of PubMed, Embase, and Web of Science from inception to March 2025, supplemented by GeneReviews and OMIM references. Studies reporting PPP2R1A variants with clinical data were included. Data extraction followed PRISMA guidelines, encompassing study characteristics, genetic findings, and phenotypic features. Results: We identified 16 studies representing 60 patients with PPP2R1A-related disorders. Twenty-six distinct pathogenic variants were identified; these were predominantly de novo heterozygous missense changes clustering within HEAT repeats 5-7. Recurrent hotspots included p.Arg182Trp (n = 12) and p.Arg183Gln (n = 5). Developmental delay and intellectual disability were universally present in all patients for whom data were available (100%, 58/58). Epilepsy occurred in 50.9% (29/57), and structural brain abnormalities in 83.1% (49/59), with corpus callosum abnormalities (40.7%, 24/59) and ventriculomegaly (32.2%, 19/59) being most frequent. Microcephaly was reported in 17.2% (10/58) and…
How strong is the evidence?
Evidence Hub reads this as a systematic review, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 60 participants or records.
Read the paper
Related studies
- Understanding the factors influencing fall armyworm (Spodoptera frugiperda J.E. Smith) damage in African smallholder maize fields and quantifying its impact on yield. A case study in Eastern Zimbabwe
- Alarming situation of emerging H5 and H7 avian influenza and effective control strategies
- Livestock and food security: vulnerability to population growth and climate change
- Atmosphere–ocean oxygen and productivity dynamics during early animal radiations
- Characterization of the global distribution and diversified plasmid reservoirs of the colistin resistance gene mcr-9
- The global seroprevalence of Toxoplasma gondii in pigs: A systematic review and meta-analysis
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.