WHIM syndrome in a child without the classic tetrad: a case confirmed by de novo CXCR4 mutation

WHIM syndrome is a rare autosomal dominant primary immunodeficiency characterized by the classical tetrad of warts, hypogammaglobulinemia, infections, and myelokathexis. The majority of cases are associated with gain-of-function mutations in the CXCR4 gene. Recent studies have expanded the clinical spectrum of the disease, revealing that only a subset of patients present with all four hallmark features. This underscores the syndrome's variable expression and the need for greater clinical awareness of its atypical forms.

We report a case of a 6-year-old Saudi girl who presented with persistent neutropenia, recurrent upper respiratory infections, and an episode of thrombocytopenia following a dental procedure. She did not exhibit warts, hypogammaglobulinemia, or myelokathexis. Immunological workup revealed marked lymphopenia affecting T, B, and NK cells, while immunoglobulin levels remained within normal limits. Bone marrow findings were unremarkable. Whole-exome sequencing identified a heterozygous de novo CXCR4 frameshift mutation (c.1172_1173del), confirming the diagnosis of WHIM syndrome. The patient was clinically stable and managed conservatively with precautions.

This case contributes to the evolving understanding of the clinical variability in WHIM syndrome and highlights the importance of genetic testing in patients with unexplained neutropenia and recurrent infections, even in the absence of the complete clinical tetrad.