Constitutional Ring Chromosomes in Greek Pediatric Patients: A 50-year Single-center Cytogenetic Study

Ring chromosomes (r) are rare cytogenetic circular structures associated with highly heterogeneous clinical phenotypes, primarily resulting from dynamic ring instability and mosaicism, as well as, unbalanced gene dosage. Consequently, establishing precise genotype-phenotype correlations in individuals with ring chromosomes remains challenging.

We performed a retrospective, single-laboratory study to investigate constitutional ring chromosomes identified by conventional cytogenetic analysis spanning the last 50 years.

Twenty-five patients carrying constitutional ring chromosomes were identified and details of each are provided. Twelve cases involved autosomal-derived ring chromosomes with r(22) being the most frequent. Five cases were mosaics, whereas seven were non-mosaic. Molecular confirmation was obtained in six cases, while a de novo origin was determined in another six. Additionally, thirteen female patients were identified with mosaic ring X chromosomes, each presenting one cell line carrying a non-supernumerary ring X chromosome (46,X,r(X)) and another with monosomy X (45,X). In four individuals, the origin of the X ring chromosome was confirmed using FISH, while a de novo origin was demonstrated in six cases.

Conventional karyotyping remains the gold-standard method for detecting ring chromosomes, recognizing their origin, evaluating mosaicism and identifying secondary instability at the single-cell level. Nevertheless, complementary advanced cytogenomic approaches are essential for improving diagnosis, refining genotype-phenotype correlations, and improving genetic counseling, risk assessment, and overall clinical management.