José Furtado

Trisomy 15 mosaicism: Challenges in prenatal diagnosis

Keywords: trisomy 15 mosaicism; fetal mosaicism; chorionic villi; prenatal cytogenetics; SNP-array; uniparental disomy

Discordant Chromosome Placental Mosaicism in a Dichorionic Twin Pregnancy

Chorionic villus sampling (CVS) is now well established as aninvasive test for prenatal diagnosis of chromosome abnormalitiesand some authors argue that this first-trimester procedurehas several advantages over mid-trimester amniocentesis in twinpregnancies [Brambati et al., 2001]. Since twin gestations seem tohave a higher risk of chromosome aberrations when compared tosingleton pregnancies, some centers now offer the possibility offirst-trimester prenatal diagnosis using CVS, including molecularrapidaneuploidy(MRA)testingbyQF-PCRormultiplexligation-dependent probe amplification (MLPA). CVS may provide thepossibility of an earlier result which may be crucial for patientreassurance and pregnancy management but has the disadvantageoftheoccasionalpresenceofplacentalmosaicism,inaround1–2%of cases, that can result from analyzing a tissue chromosomallydifferent from that of the fetus [Ledbetter et al., 1992; Farraet al., 2000]. This mosaicism may affect only the placenta—confined placental mosaicism (CPM)—or extend to the fetus—true fetal mosaicism (TFM)—in the same or in a different degreefrom the one found in the placenta [Kalousek et al., 1989; Gratietal.,2006].CPMoccursasoneofthreeforms:(i)theabnormalcelllineisconfinedtocytotrophoblast(typeI);(ii)oritonlyaffectsthestromalvillouscore(mesenchyme;typeII);(iii)oritinvolvesboth(typeIII)[Gratietal.,2006].Non-mosaicismforeitherdiploidyoraneuploidyispossibleinthefetus.Thekaryotypeofthecelllineagesisusuallyobtainedbydirectpreparations/short-term(cytotropho-blast) or long-term (mesenchyme) CVS cultures. MRA testing ispossible and is thought to test a mixture of DNAs from both thevillouscytotrophoblastandmesenchymalcore[Mannetal.,2007].However, this may yield discrepant results from the full chromo-someanalysisdependingonthemethod,thelevelofmosaicismandthetypeoftissueusedforanalysis.Thedisomy–trisomymosaicismmay have a mitotic (CPM types I and II) or a meiotic origin(CPM type III). The latter is associated with an increased risk ofpregnancy complications and fetal uniparental disomy (UPD)[Grati et al., 2006]. The detection of mosaicism for the commonautosomal trisomies in prenatal samples is relatively rare but hasbeen reported previously, as well as false-positive findings oftrisomy 18 mosaicism in CVS analysis [Schuring-Blomet al., 2002]. On the other hand trisomy 2 is one of the mostfrequently involved trisomies in pseudomosaicism both in amni-otic fluid (AF) and CVS cultures [Benn and Hsu, 2004; Sifakisetal.,2010].ToourknowledgethisisthefirstreportofadiscrepantCPMinadichorionic(DC)twinpairthatinvolvesatrisomy18anda trisomy 2.The patient was a 31-year-old, primigravid woman with DCtwins,conceivedafteraninvitrofertilization(IVF)procedureduetosequelaefrompreviouspelvicinflammatorydisease.Ultrasoundexamination (USE) at 11 weeks showed an umbilical hernia/smallomphalocele in twin B and a smaller crown-rump length (CRL;39 mm vs. 48 mm in twin A, 20th and 50th centile, respectively).First trimester aneuploidy screening on the basis of maternal ageand fetal nuchal translucency yielded normal results for twin A(1/2,499) and not calculable for twin B because the CRL was<45 mm. Since an ultrasound abnormality and early growth