Combined immunodeficiency in a patient with mosaic monosomy 21

Monosomy 21 is an extremely rare genetic disorder presenting with a wide array of symptoms. Recurrent infections, some life threatening, have been reported in several monosomy 21 patients and attributed to an, as of yet, undefined immunodeficiency. Here we report on a 3-year-old boy with mosaic monosomy 21 who presented with clinical and laboratory evidence of immunodeficiency. Despite suffering from infections highly suggestive of a cell-mediated immune defect, the patient’s T cells displayed normal counts, subsets and proliferation capability. T cell receptor repertoire was diverse, and de novo T cell production was intact. Consistent with earlier case reports, our patient displayed mildly low B cell counts with hypogammaglobulinemia. B cell subsets demonstrated mainly naïve and marginal zone B cells that have not undergone class switch. Subsequently, IgG, IgA and IgE levels were near absent, whereas IgM level was normal. De novo B cell production and B cell receptor diversity were normal. Together, these results are indicative of a defect in immunoglobulin class switching as the principal cause of immunodeficiency in monosomy 21. A better understanding of the immunodeficiency in this syndrome will enable targeted treatment and prevention of infections in order to prevent morbidity and mortality in these patients.