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TRISOMY 15 MOSAICISM
Complete trisomy 15 is a lethal abnormality and thus trisomy 15 detected in a normally developed embryo at a 10-12 week CVS sample is usually confined to placental tissues. Trisomy 15 was found in 34/126465 (0.027%) of CVS samples from the ‘ Collaborative Research on Mosaicism in CVS’. Based on amniocentesis results in these 34 cases, 28 were diagnosed as confined placental mosaicism (CPM), 1 as true fetal mosaicism, and 5 could not be classified. Thus true fetal mosaicism for trisomy 15 is quite rare, but when detected is at a high risk of developmental abnormalities. Nonetheless, based on the small sample of reported cases, a normal outcome appears to be just as likely as an adverse outcome. Whether or not the trisomic cells are confined to the placenta, uniparental disomy for chromosome 15 is a significant concern (see below) and should be tested for.
Trisomy 15 detected on CVS
Trisomy 15 found on CVS should be followed up with amniocentesis and UPD testing as well as evaluation by ultrasound. In the absence of any positive findings in these follow-up tests the prognosis for pregnancy outcome is very good.
Trisomy 15 detected on amniocentesis
Hsu et al. (1997) summarized 11 cases of trisomy 15 mosaicism detected at amniocentesis. Of these, 4 pregnancies resulted in apparently normal liveborns; 1 was born at term but had IUGR plus multiple heart defects and died at 13 days; while the remaining 6 pregnancies were terminated. Of the terminations, 5 had abnormalities while one appeared grossly normal. A higher percentage of abnormal cells in the amniotic fluid appeared to correlate with a worse outcome. fetal blood sampling is however not considered to be useful for prediction of outcome as the trisomic cells are generally not detected in fetal blood.
Uniparental Disomy (UPD 15)
Because imprinting effects are known for both maternal and paternal UPD 15, DNA studies are always suggested when prenatal diagnosis indicates trisomy 15 mosaicism. Maternal UPD is associated with Prader Willi syndrome while paternal UPD leads to Angelman syndrome. As most trisomy 15 is due to an error in maternal meiosis, maternal UPD 15 is the main concern.
Maternal UPD15 was diagnosed in 2 of 4 cases of trisomy 15 mosaicism detected on amniocentesis (Hsu et al, 1997) and 2 of 13 cases for which trisomy 15 was present in CVS samples only (Christian et al, 1996, Eucromic 1999).
Link to What is UPD?
Link to Maternal UPD 15
Link to Paternal UPD 15
Internet Links
References
(1999) Trisomy 15 CPM: probable origins, pregnancy outcome and risk of fetal UPD: European Collaborative Research on Mosaicism in CVS (EUCROMIC) Prenatal Diagnosis. 19( 1): 29-35 PubMed
Bennett CP, Davis T, Seller MJ. (1992) Trisomy 15 mosaicism in an IVF fetus. Journal of Medical Genetics 29(10):745-746. PubMed
Christian SL, Smith AC, Macha M, Black SH, Elder FF, Johnson JM, Resta RG, Surti U, Suslak L, Verp MS, Ledbetter DH. (1996) Prenatal diagnosis of uniparental disomy 15 following trisomy 15 mosaicism. Prenatal Diagnosis 16(4):323-332 PubMed
Hsu LY, Yu MT, Neu RL, Van Dyke DL, Benn PA, Bradshaw CL, Shaffer LG, Higgins RR, Khodr GS, Morton CC, Wang H, Brothman AR, Chadwick D, Disteche CM, Jenkins LS, Kalousek DK, Pantzar TJ, Wyatt P. (1997) Rare trisomy mosaicism diagnosed in amniocytes, involving an autosome other than chromosomes 13, 18, 20, and 21: karyotype/phenotype correlations. Prenatal Diagnosis 17(3):201-242. PubMed
Ledbetter DH, Engel E. (1995) Uniparental disomy in humans: development of an imprinting map and its implications for prenatal diagnosis. Human Molecular Genetics 4:1757-1764 PubMed
Markovic VD, Chitayat DA, Ritchie SM, Chodakowski BA, Hutton EM. (1996) Trisomy 15 mosaic derived from trisomic conceptus: report of a case and a review. American Journal of Medical Genetics 61:363-370 PubMed
Roberts E, Stevenson K, Cole T, Redford DH, Davison EV. (1997) Prospective prenatal diagnosis of Prader-Willi syndrome due to maternal disomy for chromosome 15 following trisomic zygote rescue. Prenatal Diagnosis 17(8):780-783. PubMed
Zaslav AL, Fallet S, Brown S, Ebert R, Fleischer A, Valderama E, Fox JE. (1998) Prenatal diagnosis of low level trisomy 15 mosaicism: review of the literature. Clinical Genetics 53(4):286-292. PubMed |