Figure - available from: Molecular Cytogenetics
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GTG-banded karyotype at birth showing A trisomy 18, B trisomy 21 and C trisomy 21,+mar. FISH study at birth showing interphase nuclei with D trisomy 18 in AQUA and chromosome X in green and E trisomy 21 in orange
Source publication
Background
Double aneuploidy is common, especially in products of conception, frequently involving a combination of a sex chromosome and an acrocentric chromosome. Double autosomal trisomies are rare with only five cases reported. Double aneuploidy mosaicism involving two different cell lines is rarer with only three cases reported.
Case presentat...
Citations
... From the literature, at least five live-born cases bearing double autosomal trisomy [+8/+14; +8/+21; +13/+18; +13/+21; and two instances of +18/+21] [12] are described. In the latter case, a combined phenotype of both trisomy 21 and trisomy 18 was noted [12]. ...
... From the literature, at least five live-born cases bearing double autosomal trisomy [+8/+14; +8/+21; +13/+18; +13/+21; and two instances of +18/+21] [12] are described. In the latter case, a combined phenotype of both trisomy 21 and trisomy 18 was noted [12]. Mosaic autosomal double aneuploidy is incredibly rare in live-born individuals [12]. ...
... In the latter case, a combined phenotype of both trisomy 21 and trisomy 18 was noted [12]. Mosaic autosomal double aneuploidy is incredibly rare in live-born individuals [12]. Notably, no such cases bearing double autosomal trisomy (non-mosaic or mosaic) were present in a historical review of live-born cases from the JHH Cytogenomics Laboratory (from the early 1960s to the present), consistent with its noted rarity in the literature. ...
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.
Background
Down syndrome is the most common and extensively studied disorder arising out of human chromosomal aberration. Several aneuploidies are associated with Down syndrome, but double trisomy (48 XXX + 21) is rarely described.
Clinical Description
A 3-year-old girl presented with respiratory distress and a chronic history of feeding fatigue and failure to thrive. She had phenotypic features suggestive of Down syndrome and clinical signs of acyanotic heart disease in congestive cardiac failure.
Management and Outcome
Echocardiography revealed ventricular septal defect and atrial septal defect. Karyotyping showed double trisomy (trisomy 21 and XXX). Trisomy X was an incidental finding on karyotyping with no clinical features suggestive of XXX syndrome specifically at this age. The patient was managed conservatively with decongestive therapy for congestive heart failure and oral sildenafil for pulmonary hypertension. Additional evaluations were done to identify associated anomalies, and the parents were counseled.
Conclusion
Down and XXX syndromes share many clinical signs and symptoms, making karyotyping the only way to make an early diagnosis. A child having a phenotype characteristic of Down syndrome may have an unsuspected double trisomy of X chromosome along with 21 trisomy, which can only be identified by karyotyping.
