Wiskott-Aldrich Syndrome Across Three Siblings: Variable Clinical Expression and Current Understanding

Wiskott-Aldrich Syndrome (WAS) is a rare X-linked immunodeficiency characterized by microthrombocytopenia, eczema, and recurrent infections. In addition to this classical triad, recent studies have emphasized the roles of immune dysregulation, autoimmunity, chronic inflammation, endothelial dysfunction, and increased susceptibility to infections. These factors contribute to a broader disease spectrum that may involve not only bleeding complications but also, in rare instances, thrombotic events. In this review, we present three siblings from the same family affected by WAS. Two of them were genetically confirmed to carry the c. mutation in the WAS gene; however, they exhibited markedly different clinical phenotypes. One presented severe thrombocytopenia and eczema, while the other developed retinal artery occlusion and thrombotic manifestations. The third sibling, although not genetically tested, died from fulminant sepsis following splenectomy for presumed immune thrombocytopenia, with clinical findings strongly suggestive of undiagnosed WAS. Through these illustrative cases, we explore the pathophysiological mechanisms underlying WAS, focusing on platelet dysfunction, autoimmune phenomena, infection susceptibility, and vascular complications. We also briefly review current treatment options, including hematopoietic stem cell transplantation, gene therapy, and novel immunomodulatory strategies. This case-based review highlights the phenotypic heterogeneity of WAS, the limitations of genotype-based predictions, and the importance of individualized management. A better understanding of the immunologic, infectious, and vascular aspects of the disease may facilitate earlier diagnosis and guide clinical decision-making in this complex disorder.