Clinical Features of PPP2 Syndrome type R5D (Jordan’s Syndrome) to Support Standardization of Care

PPP2 syndrome type R5D, or Jordan's Syndrome, is a neurodevelopmental disorder caused by pathogenic missense variants inPPP2R5D, a beta subunit of the Protein Phosphatase 2A (PP2A) (G. Mirzaa, 2019). The condition is characterized by global developmental delays, seizures, macrocephaly, ophthalmological abnormalities, hypotonia, attention disorder, social and sensory challenges often associated with autism, disordered sleep, and feeding difficulties. Among affected individuals, there is a broad spectrum of severity, and each person only has a subset of all associated symptoms. Some but not all the clinical variability is due to differences in thePPP2R5Dgenotype. These suggested clinical care guidelines for the evaluation and treatment of individuals with PPP2 syndrome type R5D are based upon data from 100 individuals reported in the literature and from an ongoing natural history study. As more data are available, particularly for adults and regarding treatment response, we anticipate that revisions to these guidelines will be made.