Immunologic, Molecular, and Clinical Profile of Patients with Chromosome 22q11.2 Duplications

J Clin Immunol. 2023 May;43(4):794-807. doi: 10.1007/s10875-023-01443-5. Epub 2023 Feb 3.

Abstract

Purpose: Duplication of chromosome 22q11.2 due to meiotic non-allelic homologous recombination results in a distinct syndrome, chromosome 22q11.2 duplication syndrome that has some overlapping phenotypic features with the corresponding 22q11.2 deletion syndrome. Literature on immunologic aspects of the duplication syndrome is limited. We conducted a retrospective study of 216 patients with this syndrome to better define the key features of the duplication syndrome.

Methods: Single-center retrospective record review was performed. Data regarding demographics, clinical details, and immunological tests were compiled, extracted into a predetermined data collection form, and analyzed.

Results: This cohort comprised 113 (52.3%) males and 103 (47.7%) females. The majority (54.6%) of mapped duplications were between low copy repeat regions A-D (LCR22A to -D). Though T cell subsets were relatively preserved, switched memory B cells, immunoglobulins, and specific antibodies were each found to be decreased in a subset of the cohort. One-fifth (17/79, 21.5%) of patients had at least 2 low immunoglobulin values, and panhypogammaglobulinemia was found in 11.7% (9/79) cases. Four children were on regular immunoglobulin replacement therapy. Asthma and eczema were the predominant atopic symptoms in our cohort.

Conclusion: Significant immunodeficiencies were observed in our cohort, particularly in B cells and antibodies. Our study expands the current clinical understanding and emphasizes the need of immunological studies and multidisciplinary approaches for these patients.

Keywords: Chromosome 22q11.2 duplication; cardiac abnormalities; immunodeficiency; lymphocyte subsets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Child
  • Chromosome Deletion
  • Chromosomes
  • DiGeorge Syndrome* / genetics
  • Female
  • Humans
  • Male
  • Retrospective Studies
  • Syndrome

Supplementary concepts

  • Chromosome 22q11.2 Microduplication Syndrome