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TRISOMY 13 MOSAICISM
Trisomy 13 (Patau syndrome) occurs in approximately 1 in 10,000 live births and mosaic trisomy 13 is thought to account for about 5% of these cases (Eubanks et al, 1998). The phenotype of true mosaicism for trisomy 13 mosaicism is very broad. Individuals with mosaic trisomy 13 may present with a range of clinic findings, from the typical features of full trisomy 13 (severe mental retardation and multiple congenital anomalies) to more mild mental retardation or even normal intellectual function, milder physical features, and longer survival. It is rare that normal intellect is present (Delatycki et al, 1998).
The finding of mosaic trisomy 13 at prenatal diagnosis presents a difficult genetic counselling situation. Most often this finding represents trisomy 13 cells confined to the placenta, but true fetal mosaicism is possible. If there are no trisomy 13 cells at fetal blood sampling and if detailed ultrasound shows a normally developed fetus, an optimistic approach can be taken. Unfortunately, low-level mosaicism of the fetus cannot be completely excluded and neither can the possibility of some effects on the phenotype and intellectual function (Delatycki et al, 1998).
There is a theoretical possibility that the abnormal trisomy 13 cells could be found in the gonadal tissue of an individual. Those who have had a prenatal diagnosis of trisomy 13 mosaicism with normal peripheral blood follow-up should still be be offered prenatal diagnosis for his/her children, given the possibility that very low level mosaicism may include the gonads (Delatycki et al, 1998). If this were the case, the individual would be at an increased risk for having offspring with non-mosaic trisomy 13.
The range in clinical severity of trisomy 13 mosaicism is likely due to the varying proportion of trisomy 13 cells and their distribution within the body. When trisomy 13 cells are detected at amniocentesis or fetal blood sampling, it is difficult to predict which cases will be mild and which will be severe. Past reports have found a poor correlation between the percentage of abnormal cells in peripheral blood analysis and the severity of clinical outcome (Delatycki et al, 1997).
Trisomy 13 detected on CVS
Diagnosis of trisomy 13 on CVS should be followed up with amniocentesis and serial detailed ultrasound.
Smith et al (1999) summarized the findings of 11 cases of trisomy 13 detected on CVS, of which, three cases had confirmed trisomy 13 mosaicism in the fetus. Hahnemann and Vejerslev (1997) reported on 15 cases of trisomy 13 mosaicism detected on CVS. In 13 the trisomy 13 cells were confined to the placenta and the fetuses were normal. Two cases were confirmed in the fetus.
Schuring-Blom et al 2002 reported a false-postive rate of 1 of 13 for cases diagnosed with full trisomy 13 on cytotrophoblasts and 2 of 3 when diagnosed with mosaic trisomy 13.
Trisomy 13 detected on amniocentesis
Delatycki et al (1998) reported on 6 cases of trisomy 13 mosaicism detected at CVS or amniocentesis, of which two were confirmed in the fetus. Both cases present with low-level fetal mosaicism with no major phenotypic effect. One case demonstrated the potential inconsistency between sampled tissue types. In this case, amniocentesis showed mosaicism, yet skin biopsy did not. In addition, a normal karyotype was found on fetal blood sampling, yet mosaicism was found on postnatal cytogenetic analysis of cord blood.
Wallerstein et al (2000) reported on 25 cases of trisomy 13 diagnosed on amniocentesis. Ten resulted in an abnormal outcome. Of these, five cases had multiple congenital anomalies, two had intra-uterine growth retardation (IUGR) and three died in utero. There were no abnormal liveborns. In cases with greater than 50% of trisomy 13 cells in amniotic fluid, there was a 60% chance for abnormalities compared to 26% risk with less than 50% of cells were trisomy 13 (Wallerstein et al, 2000). As mentioned above, when trisomy 13 cells are detected at amniocentesis it is difficult to predict with certainty the severity of clinical outcome.
Uniparental Disomy (UPD 13)
Slater et al. (1995) found that neither maternal nor paternal UPD13 is associated with an abnormal phenotype, thus there is no indication of maternal or paternal imprinting of genes on chromosome 13.
Berend et al (1999) reported on two phenotypically normal cases of paternal UPD 13 involving isochromosomes. These cases further support that paternal UPD13 does not have an adverse effect on development.
Link to What is UPD?
Link to Maternal UPD 13 page
Link to Paternal UPD 13 page
Internet Links
- HUGO Chromosome 13 - Chromosome 13 specific sites
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Human Chromosome 13 - 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
Berend SA, Feldman GL, McCaskill C, Czarnecki P, Van Dyke DL, Shaffer LG. (1999) Investigation of two cases of paternal disomy 13 suggests timeing of isochromosome formation and mechanisms leading to uniparental disomy. American Journal Medical Genetics 82(3):275-81 PubMed
Delatycki M, Gardner RJ. (1997) Three cases of trisomy 13 mosaicism and a review of the literature. Clinical Genetics 51(6):403-7. PubMed
Delatycki MB, Pertile MD, Gardner RJ. (1998) Trisomy 13 mosaicism at prenatal diagnosis: dilemmas in interpretation. Prenatal Diagnosis 18(1):45-50. PubMed
Eubanks SR, Kuller JA, Amjadi D, Powell CM. (1998) Prenatal diagnosis of mosaic trisomy 13: a case report. Prenatal Diagnosis 18(9):971-4. PubMed
Hahnemann JM, Vejerslev LO. ( 1997) European collaborative research on mosaicism in CVS (EUCROMIC)--fetal and extrafetal cell lineages in 192 gestations with CVS mosaicism involving single autosomal trisomy. American Journal of Medical Genetics 70(2):179-87. PubMed
Jarvela I, Savukoski M, Ammala P, von Koskull H. (1998) Prenatally detected paternal uniparental chromosome 13 isodisomy. Prenatal Diagnosis 18(11):1169-73. 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
Slater H, Shaw JH, Bankier A, Forrest SM, Dawson G. (1995) UPD 13: no indication of maternal or paternal imprinting of genes on chromosome 13. Journal of Medical Genetics 32(6):493 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
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 |