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TRISOMY 20 MOSAICISM
Complete trisomy 20 is not viable, and trisomy 20 ascertained through chorionic villus sampling is remarkably rare. Nonetheless, trisomy 20 is one of the more common mosaic trisomies detected on amniocentesis. Outcome of prenatally detected trisomy 20 mosaicism is normal in 90-95% of cases. Trisomic cells are virtually never confirmed in newborn blood and only rarely are found in other fetal tissues samples. However, an abnormal outcome has been noted in 5-10% of the reported cases of trisomy 20 detected on amniocentesis. Abnormal outcomes found include unexplained fetal demise, intrauterine growth restriction (IUGR) and multiple congenital anomalies. There may be a weak association been percentage of trisomic cells detected on amniocentesis and risk of outcome, but outcome is generally normal even when high levels of trisomic cells are observed. Neither repeat amniocentesis nor fetal blood sampling is considered useful to help predict outcome. High resolution ultrasound may be recommended to monitor the pregnancy.
Trisomy 20 detected on CVS
Trisomy 20 seems to be more often detected in direct CVS analysis than in CVS cultures. The amniocentesis result and outcome of pregnancy has mostly been normal in these instances.
Trisomy 20 detected on amniocentesis
There have been several large reviews of the outcome of trisomy 20 mosaicism detected on amniocentesis (Wallerstein et al, 2000; Hsu et al, 1998; Hsu et al, 1987; Hsu et al, 1991). Abnormal outcome was observed in 10/152 (6.5%) of cases reviewed in Wallerstein et al (2000). Outcome was normal in most cases even if >50% of the cells detected on amniocentesis showed trisomy 20. Twelve normal liveborns were followed beyond the newborn period. None had neurodevelopmental problems.
In the study of Hsu et al. ?166 cases of trisomy 20 mosaic pregnancies were studied. 132 were associated with a normal phenotype and 12 were associated with an abnormal phenotype. Of the abnormal outcomes – facial dysmorphism was observed in 6, urinary tract anomalies in 3 and congenital heart defects in 2. 31 had follow-up for one year or more and 12 were followed for two or more years, all were reported to be normal, except for two with borderline psychomotor delay.
We reported 6 additional cases (Robinson et al. 2005). The four cases with low levels of trisomy in amniotic fluid (0%, 10%, 11%, and 12%) were associated with a normal outcome. The remaining two cases of trisomy 20 had high levels of trisomy in amniotic fluid (96% and 58%) and had abnormal outcomes (developmental delay in one and stillbirth with IUGR and severe oligohydramnios in the other). Including previously published cases, there is a clear association with the level of trisomy and outcome, with only 4% abnormal outcomes when <40% trisomic cells were detected. Higher levels of trisomy were also observed in male fetuses as compared to female fetuses (p = 0.01); however, there were no sex differences in frequency of abnormal outcomes.
Concise reccomendations regarding prenatal counselling are provided by Bianca et al. 2005.
Uniparental Disomy (UPD 20)
Too few cases with UPD20 have been identified to come to a conclusion as to the consequences of imprinting effects, especially as all were ascertained because of an abnormal phenotype. However imprinting effects at least for the GNAS1 gene, mapping to this chromosome have been reported (see e.g. Liu et al. 2000). Eggerman (2001) found maternal UPD20 (due to a maternal Meiosis I error) in one of 51 patients investigated for unexplained intra-uterine and postnatal growth restriction. Birthweight was <3rd centile and length was <10th centile. At the age of 17 months he showed macrocephaly, strabismus, and clinodactyly of both hands. No other problems were reported. Another case of maternal UPD20 was found in a patient with growth retardation, slight dysmorphism and hyperactivity (Chudoba et al, 1999). A case of paternal UPD20 was reported in an abstract (Spinner et al, 1994) but has not been published. An additional case of partial paternal UPD20 (involving only the 'q' arm) was reported by Bastepe et al. in a patient with renal parathyroid hormone resistance (pseudohypoparathyroidism), presumably due to lack of the maternal copy of GNAS1.
It appears however that UPD20 is rare overall in trisomy 20 mosaicism (discussed in Robinson et al. 2005)
Link to What is UPD?
Link to Maternal UPD 20
Link to Paternal UPD 20
Internet Links
- HUGO Chromosome 20 - Chromosome 20 specific sites
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Human Chromosome 20 - 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
Bastepe M, Lane AH, Juppner H (2001) Paternal uniparental isodisomy of chromosome 20q--and the resulting changes in GNAS1 methylation--as a plausible cause of pseudohypoparathyroidism. Am J Hum Genet 68:1283-1289.
Bianca S, Ingegnosi C, Tetto C, Cataliotti A, Ettore G.(2005) Prenatally detected trisomy 20 mosaicism and genetic counseling. Prenat Diagn. 2005 Aug;25(8):725-726. (no abstract)
Chudoba I, Franke Y, Senger G, Sauerbrei G, Demuth S, Beensen V, Neumann A, Hansmann I, Claussen U. (1999) Maternal UPD 20 in a hyperactive child with severe growth retardation. European Journal of Human Genetics 7(5):533-40. PubMed
Hsu LY. Prenatal diagnosis of chromsomal 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
Hsu LY, Kaffe S, Perlis TE. (1987) Trisomy 20 mosaicism in prenatal diagnosis--a review and update. Prenatal Diagnosis 7(8):581-96. PubMed
Hsu LY, Kaffe S, Perlis TE. (1991) A revisit of trisomy 20 mosaicism in prenatal diagnosis--an overview of 103 cases. Prenatal Diagnosis 11(1):7-15. 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
Liu J, Litman D, Rosenberg M, Yu S, Biesecker L, Weinstein L (2000) A GNAS1 imprrinting defect in pseudohypoparathyroidism type IB. J Clin Invest 106:1167-1174.
Reish O, Wolach B, Amiel A, Kedar I, Dolfin T, Fejgin M. (1998) Dilemma of trisomy 20 mosaicism detected prenatally: is it an innocent finding? American Journal of Medical Genetics. 77(1):72-5. PubMed
Robinson WP, McGillivray B, Lewis ME, Arbour L, Barrett I, Kalousek DK. Related (2005) Prenatally detected trisomy 20 mosaicism. Prenat Diagn. 25(3):239-44. 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 |