The description of
isochromosomes 18 has so far mainly been by cytogenetic studies and based on identical banding pattern of the two arms. However, only molecular techniques are capable to distinguish an
isochromosome from a translocation, whole arm or reciprocal, between two chromosomes 18. We have used 23 PCR-based
DNA polymorphisms to determine the parental origin and mechanisms of formation in four patients with
isochromosomes 18q and to demonstrate that they were consistent with true
isochromosomes. Three of the probands were liveborn children with clinical features characteristic of
Edwards syndrome, one proband was a fetus diagnosed at prenatal diagnosis. In one case the
isochromosome was monocentric with two identical q arms of maternal origin, formed by misdivision of the centromere and loss of p arm material. Another monocentric case had 47 chromosomes with
isochromosomes i(18p) and i(18q) formed by maternal postzygotic centromeric misdivision and segregation of both
isochromosomes, or by meiosis II centromeric misdivision and nondisjunction (without recombination in meiosis I). In two cases, the
isochromosomes were dicentric with genetically identical arms composed of a part of the short and the whole long arm of chromosome 18 of paternal origin. The formation of the fused chromosomes can be explained by postzygotic exchange of sister chromatids on the short arm of chromosome 18, followed by breakage and U-shape reunion of sister chromatids.