Clinical features of PPP2 syndrome type R5D (Jordan's syndrome) to support standardization of care.

Jordan's syndrome is a rare genetic condition that affects brain development. Children with this condition may have developmental delays, seizures, larger head size, eye problems, low muscle tone, attention difficulties, and challenges with social interaction and sensory processing that are often linked to autism. They may also have sleep and feeding problems. Symptoms vary greatly between children - some are more severely affected than others.

This study presents clinical care guidelines for PPP2 syndrome type R5D (Jordan's syndrome), a rare neurodevelopmental disorder caused by genetic variants in the PPB gene affecting Protein Phosphatase 2A. Based on data from 100 individuals, the research characterizes key features including global developmental delays, seizures, macrocephaly, ophthalmological abnormalities, hypotonia, attention disorders, and social/sensory challenges often associated with autism. The condition also involves sleep disorders and feeding difficulties. Clinical presentation varies significantly between individuals, with severity differences partially explained by genetic variations.

The guidelines aim to standardize care approaches, though the authors acknowledge limitations in current data, particularly for adult populations and treatment responses.

Clinicians should consider PPP2 syndrome in differential diagnosis when autism features co-occur with seizures, macrocephaly, and developmental delays. Requires multidisciplinary care approach addressing neurological, developmental, sensory, and behavioral needs. Genetic testing may inform individualized care planning.

Guidelines based on literature review and ongoing study data rather than controlled trials. Limited data available for adult populations and treatment response outcomes. No specific sample size reported for the current analysis.

PPP2 syndrome type R5D, or Jordan's syndrome, is a neurodevelopmental disorder caused by pathogenic missense variants in, a β-subunit of the Protein Phosphatase 2A (PP2A). 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, of the clinical variability is due to differences in thegenotype.

These suggested clinical care guidelines for the evaluation and treatment of individuals with PPP2 syndrome type R5D are based on 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.