TRISOMY 18 MOSAICISM
Trisomy 18 is one of the few trisomies which can survive to term in an apparently non-mosaic state. Therefore the risk of fetal involvement when trisomy 18 is diagnosed prenatally is greater than for other trisomies. Nonetheless, trisomy 18 can sometimes be confined to placental tissues and result in a normal term birth.
Trisomy 18 detected on CVS
Smith et al (1999) summarized the findings of a large series of cases of trisomy 18 diagnosed on CVS in the U.K.. Some data from a previous U.S. study (Ledbetter et al. 1992) are also summarized in this paper. Of 67 cases with a non-mosaic (100%) trisomy on CVS--fetal involvement was confirmed in all cases based on presence of trisomy in amniotic fluid, fetal blood, or fetal tissues. However, one case showed a 100% trisomy in direct CVS samples (trophoblast) but not in cultured CVS (stroma) while several cases showed 100% trisomy 18 on cultured CVS but not in direct samples. Thus it is likely that in rare instances a diagnosis of non-mosaic trisomy in CVS may not be confirmed in the fetus. Indeed Breed et al. 1991 reported failure to confirm the trisomy in 1 of 5 such cases of trisomy 18 examined and Schuring-Blom et al (2002) report false positives in 5 of 30 cases of full trisomy 18 diagnosed on cytotrophoblasts.
In contrast, of 19 cases of mosaic trisomy 18 detected on CVS, only five cases could be confirmed to have trisomy 18 mosaicism in the fetus. Thus, while risk is high, outcome is more often good than not in this situation. In four cases from the U.K. study in which the fetus was confirmed to carry trisomic cells, the level of trisomy diagnosed on cultured CVS had ranged from 0 to 100%. In 11 cases of presumed confined placental mosaicism, the level of trisomy diagnosed in cultured CVS had ranged from 4 to 67%. Of these 11 cases one pregnancy was terminated, in one outcome was unknown, and in the remaining 9 the pregnancy resulted in a normal live born baby. Although long-term follow-up of these cases is unavailable, if the trisomic cells were truly confined to the placenta, one would expect it to be good.
Trisomy 18 detected on amniocentesis
In a study of 31 cases of trisomy 18 mosaicism detected on amniocentesis reported by Wallerstein et al. 2000. Outcomes were as follows:
- Normal liveborns - 3 (Average of 9% trisomic cells in A.F.; range 2-20%)
- Normal abortus – 11 (Average of 41% trisomy; range 7-90%)
- Abnormal liveborns – 0
- Abnormal abortus – 17 (Avergae of 37% trisomy; range 2-95%)
The abnormalities included: multiple congenital anomalies in 10 cases, dysmorphic facies in 2 cases, unexplained intrauterine fetal death(IUFD) in 3 cases, Intrauterine growth restriction (IUGR) in 2 cases. Followup for the normal liveborns was limited to the neonatal period. Thus while there appears to be a reasonable chance of a normal outcome, it is impossible to say if development would also be normal. However, it is encouraging that trisomy was not confirmed in follow-up studies of placenta/fetal tissues in those cases with a normal livebirth outcome.
In cases with greater than 50% amniotic fluid trisomy 18 cell line, there was a 75% chance for abnormalities compared to 52% with less than 50% mosaicism. Repeat amniocentesis was not considered useful in predicting outcome. However, risk of abnormal outcome increases with a positive finding in fetal blood (Wallerstein et al. 2000).
Trisomy 18 detected postnatally
Uniparental Disomy (UPD 18)
There are no reports of imprinted genes on chromosome 18 (Ledbetter & Engel, 1995).
What is UPD?
Hsu LY. Prenatal diagnosis of chromosomal abnormalities through amniocentesis. In Genetic Disorders and the Fetus: Diagnosis, Prevention and Treatment, 4th Edition. Ed by Milunsky A. The Johns Hopkins University Press, Baltimore and London.,1998. p.203-248 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
Schuring-Blom GH, Boer K, Knegt AC, Veriaal M, Leschot NJ.Trisomy 13 or 18 (mosaicism) in first trimester cytotrophoblast cells: false-positive results in 11 out of 51 cases.
Eur J Obstet Gynecol Reprod Biol. 2002 Mar 10; 101(2): 161-8. Pubmed
Shashi V, Golden WL, von Kap-Herr C, Wilson WG. Constellation of congenital abnormalities in an infant: a new syndrome or tissue-specific mosaicism for trisomy 18? 1996 Am J Med Genet. 62:38-41 PubMed
Smith K, Lowther G, Maher E, Hourihan T, Wilkinson T, Wolstenholme J. The predictive value of findings of the common aneuploidies, trisomies 13, 18 and 21, and numerical sex chromosome abnormalities at CVS: experience from the ACC U.K. Collaborative Study. Association of Clinical Cytogeneticists Prenatal Diagnosis Working Party. Prenat Diagn. 1999 Sep;19(9):817-26. PubMed
Southgate WM, Wagner CL, Shields SM, Cantu ES, Pai GS. Mosaic trisomy 8: a cautionary note regarding missed antenatal diagnosis. J Perinatol. 1998 Jan-Feb;18(1):78-80 PubMed
Wallerstein R, Yu MT, Neu RL, Benn P, Lee Bowen C, Crandall B, Disteche C, Donahue R, Harrison B, Hershey D, Higgins RR, Jenkins LS, Jackson-Cook C, Keitges E, Khodr G, Lin CC, Luthardt FW, Meisner L, Mengden G, Patil SR, Rodriguez M, Sciorra LJ, Shaffer LG, Stetten G, Van Dyke DL, Wang H. (2000) Common trisomy mosaicism diagnosed in amniocytes involving chromosomes 13, 18, 20 and 21: karyotype-phenotype correlations. Prenatal Diagnosis 20(2):103-22 PubMed