The genetics and clinical characteristics of constitutional ring chromosomes

Abstract

Constitutional ring chromosomes are generally believed to be the result of de novo breakage of both end-segments of a chromosome during meiosis or early postzygotic mitosis, with the ends joining to give a continuous ring. This mechanism presumes the loss of some genetic material during ring formation. Ring chromosomes thus represent deletions of genetic material. But an accurate delineation of identifiable syndromes is not possible in the majority of cases even when the patients have apparently identical ring chromosomes and phenotypic charactristics. In many patients with a ring, independent of the chromosome involved, there is a similar clinical phenotype characterized by the presence of extreme growth failure without major malformation, with only a few or no minor anomalies and mild to moderate mental retardation. This phenotype is generally referred to as "ring syndrome." The description of the features of this chromosome anomaly has to-date been based on standard cytogenetic banding techniques. However, recent observations made with novel molecular techniques have brought new insights into the nature of ring chromosomes, contributing to the understanding of the genetic and clinical consequences. This review examines constitutional rings and is based on the generally accepted "classical" knowledge but also takes into consideration new molecular findings.