16q22.1 deletion syndrome is associated with failure to thrive, recurrent infections, and developmental delays, while 1q21.1 duplication causes dysmorphia and neurodevelopmental delays. Neither has been linked to significant immune dysfunction.
A 30-year-old male with recurrent sinusitis/otitis and a complex medical history (developmental delay, club feet, cerebral palsy, severe gastroparesis, CKD, VSD, and asthma) was evaluated for immunodeficiency. He exhibited depressed IgG1, IgA, and IgM with impaired response to pneumococcal vaccination despite normal T and B cell subsets, TCR Vbeta repertoire, and lymphocyte function. Subsequent cytogenomic analysis revealed a 1.8-Mbp 1q21.1 duplication and a 5.3-Mbp 16q22.1 deletion encompassing NFAT5, a gene critical for immune cell function and cellular response to hyperosmotic stress. He remains stable on prophylactic antibiotics and is monitored for progression to CVID and CVID-associated conditions, including enteropathy.
This is the first report of immune dysfunction associated with either 16q22.1 deletion or 1q21.1 duplication. We propose NFAT5 haploinsufficiency as a potential mechanism for his humoral immune deficiency. Future biochemical evaluation is needed to characterize these novel findings.
This case foremost highlights the utility of genetic testing in patients with recurrent infections and complex phenotypes to uncover potential links between chromosomal abnormalities and immunodeficiency. It also illustrates the growing clinical heterogeneity of the two genetic syndromes (16q22.1 deletion or 1q21.1 duplication), which now includes humoral immune deficiency.
