Trisomy 15 CPM: Probable origins, pregnancy outcome and risk of fetal UPD

Different origins for trisomy 15 mosaicism confined to the placenta have be en suggested. We have analysed the data on trisomy 15 mosaicism in EUCROMIC . Trisomy 15 mosaicism or non-mosaic fete-placental discrepancy on CVS was registered in 0.027 per cent of samples karyotyped (34/126 465): 28/34 had confined placental mosaicism (CPM)I 1/34 was probably true fetal mosaicism and 5/34 could not be classified. In 17 of the 28 pregnancies with CPM, cyt ogenetic information existed on both cytotrophoblast lineage (direct CVS pr eparation or short-term incubation) and extra-embryonic mesoderm, EEM (vill us culture). CPM was of type I (restricted to the cytotrophoblast) in 5/17 (29 per cent); type II (restricted to the EEM) in 4/17 (24 per cent) and ty pe III (both cytotrophoblast and EEM) in 8/17 (47 per cent). Testing for un iparental disomy (UPD) for chromosome IS in the fetus or child was done in nine cases, showing upd(15)mat in 1/9, and biparental inheritance in 8/9. U pd(15)mat, clinically diagnosed due to Prader Willi syndrome, but without D NA analysis, was registered in one additional liveborn child. Analysis of t hese 17 cases, in conjunction with 10 similar reports in the literature als o having cytogenetic data from both cell lineages, indicates two categories of trisomy 15 CPM. One has a high proportion of trisomic cells: often with a type III distribution, and an observed high risk of UPD and adverse preg nancy outcome. The second has lower proportions of trisomic cells, primaril y of type I or II distribution, and a lower empirical risk of UPD or pregna ncy loss. Based on this cytogenetic analysis, supported by the available DN A data, we suggest that, in contrast to trisomy 16 CPM, the trisomic cell l ine originates from a meiotic error in only about 50 per cent of cases of t risomy 15 CPM, the rest being the result of post-zygotic, mitotic non-disju nction. Despite this, we recommend amniocentesis following the finding of a mosaic or non-mosaic trisomy 15 by CVS, in order to exclude both UPD and p otential true fetal mosaicism. Copyright (C) 1999 John Wiley & Sons, Ltd.