Severe Sepsis in an Adolescent With a De Novo Variant in the EP300 Gene Associated With Rubinstein-Taybi Syndrome Type 2: A Case Report.

Rubinstein-Taybi syndrome type 2 (RSTS2) results from pathogenic variants in the EP300 gene, manifesting with intellectual disability, facial dysmorphism, and multisystem anomalies. Variants of uncertain significance (VUS) require family segregation studies for reclassification. A 17-year-old male adolescent with intellectual developmental disorder and autism spectrum disorder (ASD) presented at the age of 12 with pneumonia complicated by severe infection, bilateral pleural effusion, and rupture of the left renal excretory system. A multigene panel identified a VUS in the EP300 gene (c.4331_4332delinsGA; p.Asp1444Gly). Family segregation analysis demonstrated a de novo origin, allowing reclassification as likely pathogenic and establishing the diagnosis of RSTS2. This case highlights the value of family segregation analysis for VUS reclassification in autosomal dominant disorders. The associated urinary abnormalities and severe infectious manifestations reinforce the importance of multidisciplinary assessment and long-term follow-up in patients with RSTS2.