Abstract
BACKGROUND: Klinefelter Syndrome (KS) and Turner Syndrome (TS) are the two most common sex chromosome aneuploidies (SCAs). This study aims to investigate genotype-phenotype correlations of SCAs including classic, rare variants, and mosaic cases of KS and TS. METHODS: To understand the relationship between genotype and phenotype (i.e., clinical findings) in SCAs, retrospective cytogenetic and clinical data was collected for KS (n = 57) and TS (n = 92) cases from 2013 to 2022. The cohorts of KS and TS were divided into three subcategories (classic, mosaic, variant/other) based on the genotype. RESULTS: The other supernumerary SCA (sSCA) group within the KS cohort had a significantly higher rate of developmental delay when compared to other KS groups. Although tall stature, pubertal delay, and congenital heart defects were described in the KS classic and other sSCA cohorts, these phenotypes were not seen in KS mosaics. Within the TS variant cohort, phenotype severity (i.e., number of accumulated pathologic clinical findings) was related to the complexity of the structural abnormality of X chromosomes. CONCLUSION: Our study highlights that the SCA genotype (classic, mosaic, variant/other) modulates expression of the phenotype. Analysis of larger datasets may provide a deeper understanding leading to enhanced care management and improved patient outcomes.