Méndez-Rosado LA, Quiñones MO, Molina GO, González GN, González MS, Maceiras RL, Bravo Y

Language: English
References: 41
Page: 27-34
PDF size: 222.57 Kb.

ABSTRACT

Introduction: Antenatal cytogenetic testing was started in Havana in 1984, as a diagnostic option for fetal chromosome complement. The techniques applied are amniocyte culture, chorionic villus sampling, cordocentesis and fluorescence in situ hybridization in interphase cells.
Objetive: Describe the results of antenatal cytogenetic testing in the cytogenetic laboratory of the Cuba's National Medical Genetics Center in Havana, from 1984 through 2012.
Methods: A retrospective descriptive study was carried out of the 22,928 pregnant women who had antenatal testing with conclusive results during the period 1984–2012. Information was obtained from laboratory databases for four antenatal diagnostic techniques. Variables studied were: antenatal diagnostic method, indications for genetic testing, type of chromosomal abnormality detected and couple's decision concerning pregnancy continuation if hereditary disease was diagnosed. Results were reported in absolute numbers and percentages.
Results: Overall positivity was 2.8% (641 cases). Of the total, 20,565 samples were from amniocyte culture (558 positive cases, 2.7%); 1785 chorionic villus sampling (38 positive, 2.1%); 407 cord blood culture (28 positive, 6.9%); and 171 fluorescence in situ hybridization in interphase cells (17 positive, 9.9%). Advanced maternal age was the predominant indication for amniocyte culture and chorionic villus sampling. Positivity was higher for the two less frequently used methods, cordocentesis (6.9% positivity) and fluorescence in situ hybridization (9.9%). The predominant chromosomal abnormality was Down syndrome, with 45.4% of cases detected (291/641; 279 pure lines and 12 mosaic trisomies), followed by Edward syndrome with 12% (77/641, 71 pure lines and 6 mosaics) and Patau syndrome 4.7% (30/641, 27 pure lines and 3 mosaics). Sexual aneuploidy with pure lines affected 6.9% of cases (44/641) and with mosaicism 4.7% (30/641). Structural chromosomal abnormalities were detected in 22.5% of cases (144/641); of these, 70.8% (102/144) were balanced and 29.2% (42/144) unbalanced. In 78.6% of cases (504/641) with chromosomal abnormalities, whether mosaic or pure, the couple opted to terminate pregnancy.
Conclusions: Antenatal cytogenetic testing has helped reduce chromosomal abnormalities, mainly in Havana, and has provided reassurance of chromosomally normal children for couples at high genetic risk. The percentage of continuing pregnancies after a diagnosis of major chromosomal abnormality has been low, supporting evidence of broad population acceptance of abortion as an option when severe genetic abnormalities are present.

REFERENCES

1. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol. 2007 Jan;109(1):217–27.

2. Nielsen J, Wohlert M. Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Hum Genet. 1991 May;87(1):81–3.

3. Stoll C, Alembik Y, Dott B, Roth MP. Study of Down’s syndrome in 238,942 consecutive births. Ann Genet. 1998;41(1):44–51.

4. Méndez LA, Quiñones O. Diagnóstico prenatal citogenético a través del cultivo de amniocitos. Rev Cubana Genet Comunit. 2009;3(1):7–15. Spanish.

5. De la Torre ME. Estudios Cromosómicos en Vellosidad Coriónica, 2199 casos en la provincia de Villa Clara. Proceedings of XV Forum Nacional de Ciencia y Técnica; 2007; Santa Clara, Villa Clara. Havana: Ministry of Public Health (CU); 2007. 20 p. Spanish.

6. Quiñones O, Nodarse A, Méndez LA, Román I, Hernández G, Palencia D, et al. Estudios citogenéticos en muestras de sangre fetal obtenida mediante cordocentesis. Primer reporte. Rev Cubana Genet Comunit. 2007;1(2):21–7. Spanish.

7. Méndez LA, Nodarse A, Morales E, Barrios A, Soriano M, Castelvi A. Diagnóstico prenatal citogenético mediante la hibridación in situ con fluorescencia. Rev Cubana Obst Ginecol. 2012 Jan–Mar;38(1):1–10. Spanish.

8. Wellesley D, Dolk H, Boyd PA, Greenlees R, Haeusler M, Nelen V, et al. Rare chromosome abnormalities, prevalence and prenatal diagnosis rates from population-based congenital anomaly registers in Europe. Eur J Human Gen. 2012 May;20(5):521–6.

9. Lippman A, Tomkins D, Shime J, Hamerton JL. Canadian multicentre randomized clinical trial of chorion villus sampling and amniocentesis. Final report. Prenat Diagn. 1992 May;12(5):385–408.

10. Loane M, Morris JK, Addor MC, Arriola L, Budd J, Doray B, et al. Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: impact of maternal age and preantal screening. Eur J Hum Gen. 2013 Jan;21(1):27–33.

11. Nagel HTC, Knegt AC, Kloosterman MD, Wildschut HIJ, Leschot NJ, Vandenbussche FPHA. [Prenatal diagnosis in the Netherlands, 1991– 2000: Number of invasive procedures, indications, abnormal results and terminations of pregnancy]. Prenat Diagn. 2007 Mar;27(3):251– 7. Dutch.

12. Kessler RG, Sanseverino MTV, Leistner-Segal S, Magalhãe JAA, Giugliani R. Prenatal diagnosis of fetal chromosomal abnormalities: Report of an 18-year experience in a Brazilian public hospital. Gen Molecular Biol. 2008;31(4):829–33.

13. Liascovich R, Rozental S, Barbero P, Alba L, Ortiz Z. [A census of medical genetics services in Argentina]. Rev Panam Salud Publica. 2006 Feb;19(2):104–11. Spanish.

14. Corral E, Moreno R, Pérez N, Ojeda ME, Campusano L, Sepúlveda W. Diagnóstico citogenético prenatal: Experiencia de 10 años en el Hospital Regional de Rancagua. Proceedings of the II International Scientific Meeting, International Society of Ultrasound in Obstetrics and Gynecology (ISUOG); 2006 Apr; Santiago de Chile, Chile. Santiago de Chile: ISUOG; 2006. Spanish.

15. Cortés F, Giannina F, Velásquez P, Be C. Prenatal cytogenetic. Rev Med Clin Condes. 2008 Jul;19(3):196–201.

16. Grether P, Cámara V, Ulloa V, Salas C, Almanza R, Kogan S, et al. Diagnóstico prenatal por amniocentesis. Experiencia clínica y citogenética en 1,500 casos. Ginecol Obstet Mex. 2010 Sep;78(9):493–503. Spanish.

17. Heredero L. Community-based program for the diagnosis and prevention of genetic disorders in Cuba. Twenty years of experience. Community Genet. 2004;7(2–3):130–6.

18. Barch MJ. ACT Cytogenetics Laboratory Manual. 2nd ed. New York: Raven Press; 1991 Aug. 640 p.

19. Luquet I, Mugneret F, Athis PD, Nadal N, Favre B, Abel C, et al. French multi-centric study of 2000 amniotic fluid interphase FISH analyses from high-risk pregnancies and review of the literature. Ann Genet. 2002 Apr– Jun;45(2):77–88.

20. Hsu LYF, Benn PA. Revised guidelines for the diagnosis of mosaicism in amniocytes. Prenat Diagn. 1999 Nov;19(11):1081–2.

21. Liehr T, Ziegler M. Rapid prenatal diagnostics in the interphase nucleus: Procedure and Cut-off Rates. J Histochem Cytochem. 2005 Mar;53(3):289–91.

22. Chitty LS. The evolution of prenatal diagnosis. Prenat Diagn. 2010 Jul;30(7):599–600.

23. Gadner RJM, Sutherland GR, Shaffer LG. Basic Concepts. In: Chromosome abnormalities and genetic counseling. 4th ed. New York: Oxford University Press, Inc.; 2011 Nov. p. 3–64.

24. Comas C, Echevarría M, Muñoz A, Rodríguez I, Carrera M, Serra B. 10 años de experiencia en diagnóstico prenatal en el Instituto Dexeus. Diagn Prenat. 2011 Oct–Dec;22(4):117–27. Spanish.

25. Smith-Bindman R, Hosman W, Feldstein VA, Deeks JJ, Goldberg JD. Second trimester ultrasound to detect fetus with Down syndrome. A meta-analysis. JAMA. 2001 Feb 28;285(8):1044–55.

26. Flood K, Malone FD. Screening for fetal anomalies with ultrasound. Curr Opin Obstet Gynecol. 2008 Apr;20(2):139–45.

27. Benacerraf BR, Barss VA, Laboda LA. A sonographic sign for the detection in the second trimester of the fetus with Down’s syndrome. Am J Obstet Gynecol. 1985 Apr 15;151(8):1078–9.

28. Borrell A. Promises and pitfalls of first trimester sonographic markers in the detection of fetal aneuploidy. Prenat Diagn. 2009 Jan;29(1):62–8.

29. Gadner RJM, Sutherland GR, Shaffer LG. Parent with a chromosomal abnormality. In: Chromosome Abnormalities and Genetic counseling. 4th ed. New York: Oxford University Press, Inc.; 2011 Nov. p. 67–111.

30. Resta RG. Changing demographics of advanced maternal age (AMA) and the impact on the predicted incidence of Down syndrome in the United States: Implications for prenatal screening and genetic counseling. Am J Med Genet A. 2005 Feb 15;133A(1):31–6.

31. Morris JK, Waters J, de Souza E. The population impact of screening for Down syndrome: audit of 19 326 invasive diagnostic tests in England and Wales in 2008. Prenat Diagn. 2012 Jun;32(6):596–601.

32. Gardner RJM, Sutherland GR. Parental Age Counseling and Screening for Fetal Trisomy. In: Chromosome Abnormalities and Genetic Counseling. 4th ed. New York: Oxford University Pres Inc.; 2011 Nov. p. 345–71.

33. Thompson & Thompson. Genética en Medicina. In: Nussbaum RL, McInnes RR, Willard HF, editors. Citogenética clínica: trastornos de los autosomas y de los cromosomas sexuales. 7th ed. Philadelphia: Elsevier Masson; 2007. p. 89–113. Spanish.

34. Hsu LYF, Yu MT, Neu RL, Van Dyke DL, Benn PA, Bradshaw CL, et al. Rare Trisomy mosaicism diagnosed in amniocytes, involving an autosome other than chromosomes 13, 18, 20, and 21: Karyotype/Phenotype correlations. Prenat Diagn. 1997 Mar;17(3):201–42.

35. Hsu LYF, Perlis TE. United States survey on chromosome mosaicism and pseudomosaicism in prenatal diagnosis. Prenat Diagn. 1984 Spring;4 Spec No:97–130.

36. Hsu LY, Kaffe S, Perlis TE. Trisomy 20 mosaicism in prenatal diagnosis—a review and update. Prenat Diagn. 1987 Oct;7(8):581–96.

37. Rojas I, González RM, Padilla M, Martín M, Lavaut K, Fuentes L. Actitudes de individuos de la población cubana hacia el aborto selectivo. Rev Cubana Gen Comunit. 2007;1(2):15–20. Spanish.

38. WHO/HGN/GL/ETH/98.1. Proposed International Guidelines on Ethical Issues in Medical Genetics and Genetic Services. Report of a WHO Meeting. Geneva: World Health Organization; 1998. p. 1–16.

39. Christianson A, Howson CP, Modell B. March of Dimes: Global Report on birth Defects. The Hidden Toll of Dying and Disabled Children. New York: March of Dimes Birth Defects Foundation (US); 2006. 18 p.

40. Méndez LA, Hechavarría D, de la Torre ME, Pimentel HJ, Hernández J, Pérez B, et al. Current status of prenatal diagnosis in Cuba: causes of low prevalence of Down syndrome. Prenat Diagn. 2014 May 24;34:1–6.

41. Reed G. Visually-impaired children in Havana: challenges of education, rehabilitation and inclusion. MEDICC Rev 2011;13(1):7–9.