Three unusual but cytogenetically similar cases with up to five different cell lines involving structural and numerical abnormalities of chromosome 18

Abstract

We report two prenatal and two postnatal diagnosed cases (the latter monozygotic twins) with ring chromosomes after GTG banding. All four, de novo r(18), cases turned out to be more complex after application of high-resolution molecular cytogenetics techniques such as use of fluorescence in situ hybridization, centromeric probes, multicolor banding, and locus-specific probes for chromosome 18. All four cases are mosaics involving chromosome 18 in up to five different cell lines, including 46,r(18); 46,dr(18); 47,r(18)x2; 46,mar(18); and 45,-18. Mosaicism sharing both numerical and structural anomalies is rare, but rings often appear as mosaics due to their mitotic instability. Overall, patients with ring chromosome 18 usually share clinical features of 18q- syndrome and, less frequently, those of 18p- syndrome. High-resolution molecular cytogenetics techniques were useful in the characterization of cases with dynamic mosaicism and in establishing the relationship between loss or gain of chromosomal material and the phenotype.

Figure 1

Case A. (A) Sonography revealed a holoprosencephaly (HPE). (B) Frontal view of the autopsy of the fetus at 17 weeks, showing the HPE. (C) Partial G-banded karyotype showing the normal chromosome 18, the single ring (r), double ring (dr), two rings, and the marker (mar) (D) Commercially available FISH subtelomeric probes (Abbott/Vysis) for chromosomes 18p (st 18p) and 18q (st 18q) demonstrated that both corresponding regions are deleted in the ring chromosome. (E) Fluorescence in situ hybridization applying subcentromeric probes revealed that the centromere-near region in 18p11.21 was absent and the centromere-near region in 18q11.21 was present on the ring. (F) Multicolor banding (MCB) confirmed the aforementioned findings.

Figure 2

Case B, MCB results. In addition to a normal chromosome 18, either a ring chromosome (r), a double ring (dr), a minute shaped chromosome (del), or an acentric fragment (ace) was present.