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TRISOMY 8 MOSAICISM
Complete trisomy 8 occurs in 0.8% of spontaneous pregnancy loss (miscarriage).
Mosaic trisomy 8 is a well described syndrome. Over 75 cases have been reported. The features are extremely variable and may be mild but also may include: mental retardation, dysmorphic facies, skeletal anomalies, congenital heart defects and kidney malformations(Webb et al, 1998).
Confined placental mosaicism (CPM) of trisomy 8 is relatively common. There is often a high proportion of trisomy 8 cells in the extra-embryonic tissue, but the majority of cases are found to have a normal fetal karyotype with the trisomy 8 cells confined to the placenta (Webb et al, 1998). CPM does not seem to present long-term consequences for the fetus (Saks et al, 1998). However, given the viability of true fetal trisomy 8 mosaicism, there should be further diagnostic testing offered in continuing pregnancies (Wolstenholme, 1996). Unfortunately, both a normal amniocentesis result and a normal fetal blood sampling result cannot completely eliminate the chance of fetal mosaicism; The detection of any abnormalities on ultrasound indicate that the fetus may be affected. On the other hand the outcome associated with low level trisomy 8 mosaicism detected in amniotic fluid or blood is also not predictable and may be normal.
Both confined and generalized mosaicsm for trisomy 8 is, in the vast majority of cases mitotic in origin, whereas most cases of trisomy 8 observed in miscarriages are due to a maternal meitoic error (Karadima et al.1998; and Robinson et al. 1999).
Trisomy 8 detected on CVS
Most cases of trisomy 8 detected on CVS are not associated with any pregnacy complications and are not confirmed at follow-up amniocentesis. In a study of 15,109 CVS evaluated over 5 years, 5 cases of trisomy 8 mosiaicsm were identified, none of which were confirmed in amniocytes (Grati et al. 2006). In another study of 92,246 CVS, trisomy 8 was found in 11 samples, of which only one was confirmed to be present in the fetus (Hahneman & Vejerslev, 1997). However, two of the 11 children had multiple malformations, including one case with trisomy 8 mosaicism on CVS culture, but a normal karyotype on CVS direct preparation and amniocentesis. In pregnancies with CVS mosaicism involving trisomy 8, high resolution serial ultrasound examination is indicated, regardless of the amniocentesis result.
Saks et al (1998) reported on a case of, what appeared to be, confined placental mosaicism for trisomy 8. The pregnancy resulted in a child with intra-uterine growth retardation (IUGR). Postnatal investigations revealed biparental inheritance of chromosome 8 and the infant exhibited no clinical features of trisomy 8 mosaicism. He experienced a period of rapid catch-up growth and showed appropriate development (Saks et al, 1998).
Some other reports of trisomy 8 mosiacism include (note single case reports may be biased towards poorer outcomes):
Robinson et al. 1997: Am J Hum Genet. : 4 cases involved trisomy 8 detected on CVS. None were confirmed in amniocentesis. Outcome was normal in one (which also had mosaic trisomy 21); outcome was unknown in one; the pregnancy was terminated in one with no autopsy findings reproted; and in one the mother experienced preeclampsioa and the baby was small at birth but no malformations were reported.
Daniel et al. 2004; Prenatl Diag. 24:524-536: One case of trisomy 8 mosaicism not confirmed in followup amnio. Normal featl U/S. Abnormal maternal serum screen results (high hCG, low PAPPA). Trisomy confirmed in amniocentesis. Pregnancy was terminated but no autopsy preformed and no abnormaliteis reproted. Maternal meiotic orgin of trisomy.
Guichet et al. 1995 Prenal Diagn. Trisomy 8 mosiacism was diagnosed on cultured CVS but not in direct preparations after abnormal findings were detected on a 12 week ultrasound. The pregnancy was terminated and autopsy confirmed the ultrasound findings.
Klein et al. 1994 Prenatl Diag 14:451-4 . Trisomy 8 mosiacism was diagnosed on cultured CVS but not in direct preparations. Amnioceneteis was normal. A peripheral blood culture after birth showed low levels of trisomy 8 mosaicism. The patient was phenotypically and developmentally normal at 30 months of age.
Trisomy 8 detected on amniocentesis
Little is known about the long term prognosis of trisomy 8 detected in amniocentesis. However, one would expect the outcomes to be better on average than those diagnosed postnatally, since postnatal trisomy 8 will likely only be detected when abnormalities are present.
Hsu et al (1997) reported on 14 cases of trisomy 8 mosaicism detected on amniocentesis. One case with 77% trisomy 8 cells was reported to be abnormal. The remaining 13 resulted in grossly normal pregnancy terminations or liveborns. The clinical diagnosis of trisomy 8 syndrome is difficult due to the subtle abnormalities associated, (e.g. thick lips, prominent ears, etc.).
Chromosome 8 carries two oncogenes, which may account for the development of cancer among some patients with trisomy 8 mosaicism (Saks et al, 1998).
Uniparental Disomy (UPD 8)
There is cuirrently no evidence of imprinted genes on chromosome 8 (Ledbetter & Engel, 1995) and prenatal testing of UPD8 is therefore not warrented.
One case of complete paternal uniparental isodisomy for chromosome 8 was identified through screening for lipoprotein lipase deficiency (Benlian et al., 1996). A case of complete maternal uniparental isodisomy 8 was identified through a routine genome scan for diabetes genes (Karanjawala et al. 2000). Both cases had normal growth and development making it unlikely that there are imprinted genes of major effect on chromosome 8. However, the maternal UPD8 case did have the unusual history of an early onset invasive ileal carcinoid tumor and also exhibited reactive arthritis and multiple pigmentary lesions. These findings could have been unrelated, related to the presence of UPD, or possibly due to cytogenetic anomalies not present in blood but related to the origin of the UPD (e.g. low level trisomy).
Link to What is UPD?
Link to Maternal UPD 8page
Link to Paternal UPD 8 page
Internet Links
- HUGO Chromosome 8 - Chromosome 8 specific sites
- Trisomy 8 Support group
- Human Chromosome 8 Homepage - The University of Houston. This page is an attempt consolidate information and resources on the physical and genetic mapping of human chromosome 8, as well as information on chromosome 8 specific genetic diseases current of interest to my research group.
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Human Chromosome 8 - Provides links to gene maps, sequences, associated genetic disorders, nonhuman genetic models, identified genes, research efforts and laboratories, and other information as available. Links are very scientific.
References
Benlian P, Foubert L, Gagne E, bernard L, De gennes JL, Langlois S, Robinson W, Hayden M. (1996) Complete paternal isodisomy for chromosome 8 unmasked by lipoprotein lipasedeficinecy. Am J Hum Genet 59:431-436.
de Pater JM, Schuring-Blom GH, Nieste-Otter MA, van Nesselrooij B, Kapitein B, Christiaens GC, Leschot NJ. (2000) Trisomy 8 in chorionic villi-unpredictable results in follow-up. Prenatal Diagnosis 20(5):435-7. PubMed
Hahnemann JM, Vejerslev LO. Accuracy of cytogenetic findings on chorionic villus sampling (CVS)—diagnostic consequences of CVS mosaicism and non-mosaic discrepancy in centres contributing to EUCROMIC 1986-1992. Prenat Diagn. 1997 Sep;17(9):801-20. PubMed
Hahnemann JM, Vejerslev LO. European Collaborative Research on Mosaicism in CVS(EUCROMIC)-Fetal and Extrafetal Cell lineages in 192 gestations with CVS mosaicism involving single autosomal trisomy. 1997 Am J Med Genet 70:179-187. 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):201-42. PubMed
Karadima G, et al. Origin of nondisjunction in trisomy 8 and trisomy 8 mosaicism. Eur J Hum Genet. 1998 Sep-Oct;6(5):432-8.
Karanjawala ZE, Kaariainen H, Ghosh S, Tannenbaum J, Martin C, Ally D, Tuomilehto J, Valle T, Collins
FS. Complete maternal isodisomy of chromosome 8 in an individual with an early-onset ileal
carcinoid tumor. Am J Med Genet 2000 Jul 31;93(3):207-10
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
Meck J, Chen TJ, Wong L-J, Imholte J, Perry K, Qin N, Baidas S. Cytogenetic and molecular evidence of constitutional mosaic trisomy 8 and hematologic abnormalities in a phenotypically normal woman. Georgetown Univ Med Ctr, Wash, DC.
Robinson WP, Bernasconi F, Lau A, McFadden DE. Frequency of meiotic trisomy depends on involved chromosome and mode of ascertainment. Am J Med Genet. 1999 May 7;84(1):34-42. PubMed
Saks E, Mccoy MC, Damron J, Kelly TE. (1998) Confined placental mosaicism for trisomy 8 and intra-uterine growth retardation. Prenatal Diagnosis 18(11):1202-4. PubMed
Webb AL, Wolstenholme J, Evans J, Macphail S, Goodship J. (1998) Prenatal diagnosis of mosaic trisomy 8 with investigations of the extent and origin of trisomic cells. Prenatal Diagnosis 18(7):737-41. PubMed
Wolstenholme J. (1996) Confined placental mosaicism for trisomies 2, 3, 7, 8, 9, 16, and 22: their incidence, likely origins, and mechanisms for cell lineage compartmentalization. Prenatal Diagnosis.16(6):511-24. PubMed |