Concomitant Chromosomal and Molecular Aberrations in Trisomy 8 Mosaicism and Associated Compound Phenotypes: Report of Three Cases and Review of Literature

Trisomy 8 mosaicism (T8M) syndrome is a rare aneuploidy condition affecting 1/25,000–50,000 live births. Affected individuals have highly variable phenotypes from very mild dysmorphism to severe structural anomalies caused by chromosomal mosaicism and possibly undetected molecular aberrations. The utilization of chromosome microarray analysis (CMA) and exome sequencing (ES) in clinical laboratories enable the identification of genomic copy number imbalances and pathogenic gene variants. We presented one patient with a double aneuploid mosaic pattern of Monosomy X and Trisomy 8 for a compound phenotype of Turner syndrome (TS) and T8M syndrome, the second patient with T8M and a mosaic pathogenic variant in the PTEN gene detected by ES, and the third patient with typical phenotypic constellation of malformations with no other genetic aberrations detected by CMA and ES. Classification of mosaic findings was provided using a recommended six‐attribute scheme. Review of the literature summarized cases of T8M with concomitant molecular defects of a deletion at 22q11.2 and pathogenic variants in the SALL1 , RECQL4 , NF1 , CASK, and PAH genes. These observations indicated that integrated cytogenetic and genomic analyses should be offered to patients with phenotypic abnormalities outside the spectrum of the T8M syndrome for comprehensive laboratory diagnosis and clinical management.