Prenatal Diagnosis of PPP2R1A-Related Neurodevelopmental Disorders Using Whole Exome Sequencing: Clinical Report and Review of Literature

PPP2R1A-related neurodevelopmental disorder (NDD) is expressed with autosomal dominant inheritance and is typically caused by a pathogenic de novo PPP2R1A mutation. It is characterized by the predominant features of hypotonia, developmental delay, moderate-to-severe intellectual disability, agenesis of corpus callosum (ACC), ventriculomegaly, and dysmorphic features; however, none of these anomalies have been diagnosed prenatally. We report on the prenatal diagnosis of PPP2R1A-related NDD in two fetuses by whole exome sequencing. Fetus 1 had partial ACC and severe lateral ventriculomegaly; the pathogenic heterozygous c.544C > T (p. Arg182Trp) de novo missense variant in PPP2R1A was detected. Fetus 2 had severe enlargement of the lateral and third ventricles and macrocephaly; they showed a heterozygous likely pathogenic mutation in PPP2R1A gene (c.547C > T, p. Arg183Trp). Both variants were de novo. This was the first study to use trio WES to prenatally analyze fetuses with PPP2R1A variants. Prenatal diagnosis will not only expand the fetal phenotype of this rare genetic condition but also allow for an appropriate counseling of prospective parents regarding pregnancy outcomes.

Automated summary

PPP2R1A-related neurodevelopmental disorder (NDD) is a rare genetic condition characterized by hypotonia, developmental delay, intellectual disability, agenesis of corpus callosum, ventriculomegaly, and dysmorphic features. This study reports on the prenatal diagnosis of PPP2R1A-related NDD in two fetuses using whole exome sequencing, which revealed pathogenic de novo mutations in the PPP2R1A gene. Prenatal diagnosis of this condition can expand the understanding of its fetal phenotype and facilitate counseling for prospective parents.