A paternally transmitted complex chromosomal rearrangement (CCR) involving chromosomes 2, 6, and 18 includes eight breakpoints and five insertional translocations (ITs) through three generations.

Complex chromosomal rearrangements (CCRs) are uncommon and mainly occur de novo. We report here on a familial CCR involving chromosomes 2, 6, and 18. The propositus is a boy first referred because of growth delays, hypotonia, and facial anomalies, suggestive of deletion 18q syndrome. However, a cytogenetic family study disclosed a balanced CCR in three generations, which was detailed by FISH using BAC clones, and consisted of eight breakpoints with five insertional translocations (ITs). The propositus had a cryptic 18q deletion and a 6p duplication. Paternal transmission of this CCR was observed through three generations without meiotic recombination. Our investigation allowed us to provide porosities counseling and management of prenatal diagnosis for propositus cousin who carries this particular CCR.

Supernumerary marker chromosomes management in prenatal diagnosis.

To assess the practical usefulness of array-comparative genomic hybridization (a-CGH) when supernumerary marker chromosomes (SMCs) are detected during prenatal diagnosis, we retrospectively studied SMC management in our laboratory before a-CGH availability. In this 11-year study, SMCs were observed in 20/16,810 routine karyotypes (0.12%). Their chromosomal origin, ascertained in 13 cases, remained elusive in seven using conventional cytogenetics and FISH. In the literature, most of SMCs (2/3) are easily identified through conventional cytogenetics and targeted FISH, and in these cases a-CGH would have been unneeded. This technique would have been less helpful in nine cases, that is, bisatellited SMC, isochromosomes and translocation derivatives. On the other hand, a-CGH would have been helpful for the 11 remaining cases. It would have improved diagnostic accuracy of six SMC whom chromosomal origin was ascertained by cytogenetics and FISH and for which prognosis was only based on literature and ultrasonographic data. Among five unidentified SMCs, a-CGH would have been more reassuring for four heterochromatic SMCs than normal ultrasonography alone and would have characterized the unidentified case associated with malformations that was interrupted. However potential pitfalls should be outlined. Using high level resolution chip expose to polymorphism detection and misinterpretation, a very sensitive problem in prenatal diagnosis. Moreover, low grade mosaicism could remain undetectable with this technique, leading to erroneous conclusions. Wisest use of a-CGH should be a complementary approach in prenatal management of SMC. It is specifically appropriate when SMC interpretation remains equivocal and only indirectly based on mode of inheritance, literature data and ultrasonography.