Pulmonary manifestations of Nijmegen breakage syndrome [NBS]

NBS is a rare inherited condition, characterized by microcephaly, chromosomal instability, immunodeficiency, predisposition to malignancy. The aim was retrospective study characterizing clinical and immunological status of NBS pts at the time of diagnosis. Materials and methods: We analyzed retrospective clinical data collected from 122 pts with NBS treated at Children9s Memorial Health Institute. Results: All pts met the diagnostic and genetic criteria of NBS. Out of 122 pts, 64 were alive at the end of 2015. Median age of the overall cohort was 14.3 yrs (1.4-33.1 yrs). Median age of death was 11.1 yrs (2.0-33.6 yrs). The humoral deficiencies predisposed NBS pts to recurrent/chronic respiratory tract infections: pneumonia 43%, acute bronchitis40%, chronic bronchitis22%, bronchiectasis18%, upper respiratory tract infections12%, sinusitis 9%, chronic sinusitis with polyps 4, fungal pneumonia4, lung TBC 2, pulmonary fibrosis 1, chronic respiratory insufficiency 1 [pts]. Most respiratory tract infectionswere caused by community-acquired pathogens. Statistical analysis showed significant correlation between severe and/or chronic respiratory tract infectionand IgG, IgG1, IgG4 and/or IgA deficiency. Predisposition to respiratory infections did not correlate with the severity of T-cell lymphocytopenia. The most common cause of death were malignancies of hematopoetic origin. The first episode of malignancy occurred at a median age of 10.25 yrs (2-26 yrs). Conclusions: Variable combined humoral and cellular immunodeficiencies and heterogeneous clinical manifestation were observed in NBS pts. Predisposition to recurrent and/or chronic respiratory tract infectionscorrelated with the severity of humoral immune deficiency.