Live-Born Double Aneuploidy at the Johns Hopkins Cytogenomics Laboratory: Case Report and Review of the Literature

Abstract

Double aneuploidy is the co-occurrence of aneuploidy of two different chromosomes within the same individual. Genomic imbalance associated with two aneuploidies in humans is associated with early lethality, and observation in live-born humans is rare. In isolation, trisomy of chromosomes 13, 18, 21, X, and Y may be better tolerated, whereas monosomy of X is the only such type of aberration that may be compatible with life. It is hypothesized that two successive malsegregation events must occur in early development to be observed constitutionally. Mechanisms like trisomy rescue or selection against aneuploidies may result in mosaicism and promote subsequent survival in live-born individuals, depending on the chromosomes involved. From the literature, double aneuploidy in the live-born is rare, with (acrocentric) autosomal with gonosomal aneuploidy more common than double autosomal aneuploidy. A retrospective case study of patients who underwent routine postnatal cytogenetic testing at The Johns Hopkins Hospital (JHH) Cytogenomics Laboratory (from its inception in the early 1960s-present) was carried out to identify mosaic and/or non-mosaic forms of double aneuploidy. One case each of non-mosaic [Klinefelter with Edwards Syndrome] and non-mosaic [Klinefelter with Down Syndrome] is identified. No gonosomal and autosomal cases in females nor double autosomal trisomies were identified in live-born individuals at the JHH Cytogenomics Laboratory. Given the advancements in non-invasive prenatal screening for common aneuploidies, the need for diagnostic confirmation studies persists. Providers should be aware of the possibility of early detection of pregnancies bearing double aneuploidy (common or rare) when maternal malignancy is not suspected. Additionally, clinicians should consider the possibility of double aneuploidy in rare situations of atypical or blended phenotypes reminiscent of dual diagnoses. Further work is needed to identify and compile these and even rarer double aneuploidy cases to improve genotype-phenotype correlations.