Ring Chromosome 6

Ring chromosome 6 (RC6) is a rare constitutional structural abnormality that generally occurs during meiosis or early post-zygotic mitosis. Most of RC6 cases occur de novo except for very rare cases having parental origin. Its preponderance is seen more in males compared to females with majority of RC6 cases identified postnatally with short stature, gross developmental delay, and variable dysmorphic features, whereas prenatal cases are often presented with intra-uterine growth retardation (IUGR) and hydrocephalus. RC6 can be identified primarily by conventional karyotype analysis followed by chromosome microarray analysis (CMA) or next-generation sequencing (NGS) to precisely identify the break points and genomic imbalances. Further identification of candidate genes within the genomic imbalances provides evidence for genotype–phenotype correlations that can be contributory to the variable degree of clinical features. Commonly observed short stature and microcephaly probably represent ‘ring syndrome’ phenotype due to dynamic somatic mosaicism; however, variable penetrance and expressivity caused by genomic imbalance for other clinical features are observed. Banding cytogenetics to define the ring structure and dynamic mosaicism followed by CMA and/or NGS to define genomic imbalances should be performed for patients with RC6, with the goals of exact breakpoint characterization and genotype–phenotype correlations.