X-Linked CGD Carrier State in a Down Syndrome Girl

Introduction Cutaneous infections are a common concern in individuals with Down syndrome, who often present with recurrent skin lesions such as folliculitis, furunculosis, and impetigo. Similarly, carriers of hemizygous variants in the CYBB gene, associated with X-linked chronic granulomatous disease (CGD), may also be more susceptible to skin infections. This case describes a female patient with both conditions, contributing to her vulnerability to recurrent skin infections. Case Description A 10-year-old girl with trisomy 21 was referred for immunological evaluation due to recurrent furuncles and abscesses in the axillary and inguinal regions, requiring frequent antibiotic treatments. Laboratory investigations showed normal neutrophil counts, as well as normal levels of T, B, and NK lymphocyte subpopulations, serum immunoglobulins, and antibody responses to vaccine antigens. A dihydrorhodamine (DHR) assay was performed with abnormal results. The histogram analysis revealed a bimodal pattern, consistent with a carrier status for X-linked CGD, and a second test confirmed this finding, with similar results. Genetic testing (NGS sequencing) identified a heterozygous deletion of 31 genes on the X chromosome (Xp21.1-p11.4), including CYBB. Conclusion Mutations in the CYBB gene cause X-linked CGD, the most common form of this phagocyte dysfunction. Female carriers can be identified by the bimodal pattern observed in the DHR assay. Although often asymptomatic, female carriers who present with a low percentage of neutrophils with normal superoxide production may present with a CGD-like phenotype, showing infectious, inflammatory, and autoimmune manifestations. The identification of carrier status in this girl with Down syndrome was crucial for managing and preventing further infections. Additionally, this finding allows for monitoring other possible complications and holds particular significance for genetic counseling.