Response: rare chromosomal complement of trisomy 21 in a boy conceived only by IVF

Abstract

Guran and colleagues describe in a letter in this issue a case of mosaic Down syndrome with a complex karyotype very similar to that described by us (Quiroga et al., 2009Quiroga R. Roselló M. Martinez F. et al.Rare chromosomal complement of trisomy 21 in a boy conceived by IVF and cryopreservation.Reprod. Biomed. Online. 2009; 19: 415-417Abstract Full Text PDF PubMed Google Scholar). These two cases are strikingly similar: both patients were conceived using assisted reproductive techniques, the two have very similar chromosomal mosaicism, both have structural anomalies of chromosome 21, namely ring(21) and der(21;21). We have no data on the exact prevalence of these anomalies but we know that they are rare. Most cases of Down syndrome are caused by free trisomy 21. Only 5% are due to translocation trisomy, and within this group almost half have 14;21 translocation, so the proportion of cases of Down syndrome caused by a translocation (21;21) must be less than 2%. Even less common is the association of both abnormalities in one patient: ring(21) and der(21;21). The possibility that in these two cases both anomalies have arisen as independent events is extremely low. Since both anomalies of chromosome 21 are rare, they are very likely related. The ring chromosome could originate from the derivative 21, or alternatively the derivative 21 is formed from the ring 21. It is difficult to know the exact mechanisms that led to this chromosome constitution. However, it is likely that assisted reproduction techniques, with or without cryopreservation of embryos, have contributed in some way to the occurrence of these chromosomal abnormalities since the only two known patients with both anomalies have been conceived through the use of these techniques. On the other hand, the only comparable case we found in the literature was the case published by Souraty et al., 2007Souraty N. Sanlaville D. Chédid R. et al.Cytogenetic investigation of a child with a mosaic isochromosome 18q and ring 18q.Eur. J. Med. Genet. 2007; 50: 379-385Crossref PubMed Scopus (6) Google Scholar that described similar chromosomal abnormalities of chromosome 18 in a patient conceived naturally. This case shows that the events giving rise to such rearrangements, although they are extremely rare, also occur naturally.