Shashi-Pena syndrome with late-onset specific hypogammaglobinaemia and autoimmune cytopenia.

PMID 40759503 | DOI 10.1136/bcr-2024-263643 · BMJ case reports · 2025

An early adolescent male with Shashi-Pena syndrome (SPS), characterised by a novel heterozygous pathogenic variant (p.Ser627Phefs*22) in the ASXL2 gene, presented with a spectrum of manifestations. These encompassed intellectual disability, severe scoliosis, unique facial dysmorphisms, congenital heart disease, recurrent infections and autoimmune cytopenia. Distinctively, this case revealed late-onset hypogammaglobulinaemia and autoimmune cytopenia, which had not been previously documented in SPS. To our knowledge, this is the first report clinically delineating immune system involvement in a patient with SPS, thereby accentuating the significance of evaluating for immunodeficiency in the presence of Additional Sex Combs-Like (ASXL) gene anomalies, particularly against a backdrop of recurrent infections and autoimmune presentations. The implications of this case encourage further investigation into the incidence and underlying mechanisms of immune dysregulation in ASXL-related syndromes, aiming to enrich the clinical understanding and enhance the therapeutic approaches for these complex conditions.