Characterization of Constitutional Ring Chromosomes over 37 Years of Experience at a Single-Site Institution

Background/Objectives: Ring chromosomes (RCs) can be rare or common depending on the chromosome involved. With interest in the historical RCs identified by our laboratory, we curated instances to provide further information to this research field. Methodology: We carried out a retrospective, single-center study of constitutional RCs identified starting in the late 1980s. Details for 40 RCs with a modal number of 46 chromosomes are featured here. Results: Mosaic and non-mosaic RCs are identified, with a preponderance of pediatric-aged females at first ascertainment. We corroborated an enrichment for acrocentric and X chromosome RCs. Six were ascertained perinatally, with peripheral blood being the most commonly studied postnatal specimen type. Notable RCs included a female fetus with an increased risk for monosomy X, whose mosaic RCY arose secondary to a translocation between the sex chromosomes. In another, a series of complex events formed three structurally aberrant chromosomes, including an RC4 with loss of 4p16.3, corresponding with the observed phenotypic expression of Wolf-Hirschhorn syndrome. In another, a mosaic RCX was co-identified with an isochromosome 21q, resulting in a dual diagnosis of trisomy 21 and Turner syndrome. In another, the atypical RC21 structure raises the possibility of a complex rearrangement. Chromosomal microarray data clarified breakpoints and gene dosage imbalances in fifteen, while low-level mosaicism for the RC escaped detection by array in another. Eight RCs were de novo, and parental exclusion was documented for six. Conclusions: This study illustrates the need for cytogenomic follow-up to improve the literature for patients with RCs.