Recurrent Panuveitis as a Manifestation of a Novel PIK3CD Gene Mutation: A Diagnostic and Management Challenge.

Abstract

Purpose: To present a unique case of recurrent panuveitis in a young patient associated with a novel pathogenic variant in the PIK3CD gene, expanding the clinical spectrum of Activated PIK3 delta syndrome (APDS), a primary immunodeficiency that predisposes individuals to infections, autoimmunity, and malignancies.

Methods: We evaluated a 15-year-old boy with refractory panuveitis, recurrent infections, and lymphadenopathy with Hodgkin lymphoma. Ophthalmic assessment and ultra-wide field fundus fluorescein angiography were conducted. Whole exome sequencing identified a novel heterozygous pathogenic variant in the PIK3CD gene. Immunological and histopathological evaluations further supported the diagnosis of APDS.

Results: The patient experienced progressive vision loss despite immunosuppressive therapy with prednisolone, methotrexate, and mycophenolate mofetil. Genetic testing revealed a novel PIK3CD pathogenic variant (c.1002C>G;p.Asn334Lys), confirmed via Sanger sequencing and predicted by in-silico tools to be pathogenic. Initial improvement was observed with steroids, but frequent relapses upon tapering underscored the chronicity of his inflammatory condition.

Conclusion: This case underscores the importance of genetic testing in diagnosing complex, treatment-resistant uveitis in children. The novel PIK3CD pathogenic variant expands the genetic landscape of APDS, indicating the need to consider underlying genetic causes in cases with recurrent systemic inflammation and infections. Managing APDS requires a careful balance of immunosuppressive treatment and monitoring for potential malignancies, emphasizing a multidisciplinary approach to optimize patient outcomes.