New diagnosis of late onset combined immune deficiency in an adult with associated 16p13.3 duplication syndrome

Abstract

Background16p13 duplication syndrome is a rare chromosomal disorder that manifests with neurocognitive delay/autism, dysmorphic features, and cardiac defects. Severe pneumonia has been documented in patients with this disorder and mostly attributed to abnormal anatomy. To date, no phenotype of immune deficiency has been linked to 16p13 duplication syndrome. Case reportHere we report a case of a 57-year-old female with history of cleft palate, dysmorphia, autism, seizure disorder, uncharacterized myopathic disorder, chronic diarrhea, volvulus, recurrent pneumonias and shingles, and a previous diagnosis of common variable immune deficiency (CVID). Patient presented to our clinic to establish care in the setting of persistent disseminated verruca and recurrent UTIs. She had hypogammaglobulinemia with absent IgA and IgM but normal IgG while on Immunoglobulin infusion (IVIG). Immunophenotyping demonstrated T and NK cell lymphopenia (CD4: 225 cells/µL; CD8: 71 cells/µL; CD56: 29 cells/µL) and absent B cells. Lymphocyte proliferation with antigen and mitogen stimulation was normal. Immune gene panel testing demonstrated three copy number variants (CNV) in CLCN7, HPS3, and SLX4 (all on Chr16) and heterozygous variants of unknown significant (VUS) in FANCI, HPS3, and UNC45A. Chromosomal microarray analysis demonstrated 4.8Mbp copy number gain in the 16p13.3 region (Chr16:383485-5220007) with a terminal 293kbp copy number loss. She remained on IVIG but passed away before additional advanced immune studies could be done. DiscussionThere are few microduplication syndromes that are associated with immune deficiencies including 16p11.2, 19p13, 20p12.2, 22q11.2, and MECP2 duplication. We established a new diagnosis of 16p13.3 duplication syndrome in an adult patient with recurrent cutaneous viral infections, pneumonias, and laboratory features consistent with late onset combined immune deficiency (LOCID). This case report adds to the existing literature on duplication syndromes and associated immune abnormalities.