INTRODUCTION The consequences of de novo balanced structural chromosome aberrations diagnosed antenatally are unpredictable, and, as a result, they introduce uncertainty into genetic counseling decisions.

OBJECTIVE Describe de novo balanced structural aberrations present at antenatal diagnosis in samples from pregnant women in five Latin American countries and determine their effect on carrier individuals.

METHODS This was a retrospective observational study based on analysis of 109,011 antenatal tests conducted from January 1981 to December 2016 in Cuba, Uruguay, Costa Rica, Mexico, and Colombia. Thirteen cytogenetic laboratories provided information that included the cases analyzed during the study period; number of de novo balanced structural aberrations diagnosed antenatally; number of diagnoses with de novo balanced structural aberrations that resulted in termination of pregnancy; detailed descriptions of the karyotypes of de novo balanced structural aberration carriers, and descriptions of the form of diagnosis, including types of samples used (amniotic fluid, chorionic villus or fetal blood). Each laboratory also provided pathology reports and genetic counseling at time of diagnosis. Postnatal followup for pregnancies carried to term continued for at least two years.

RESULTS Of the 109,011 antenatal tests studied, 72 (0.07%) showed de novo balanced structural aberrations. These events primarily involved chromosomes 1, 2, 7, 14, 18, and 20. Of the 79 breakpoints identified, the most common were 5p15.3, 7q11.2, 7q22, and 14q24. We identified three breakpoints corresponding to 3.8% (3q13.1, 3q13.2, and 9p12) that were not reported in other studies of de novo balanced structural aberrations diagnosed antenatally in patients from other geographic regions or in studies of chromosomal fragile sites. Two of these breakpoints (3q13.1 and 3q13.2) were associated with high risk of phenotypic abnormalities. Information on antenatal or postnatal followup was available for 62 (86%) of de novo balanced structural aberration carriers; of the 44 carriers with postnatal followup, 10 had phenotypic abnormalities.

CONCLUSIONS Three new de novo breakpoints were identified, presumably related to genetic admixture characteristics in Latin America. Since some diseases associated with de novo balanced structural aberrations detected antenatally have a late onset, followup for at least two years is recommended for carriers of these aberrations. The information in this study is useful in genetic counseling for pregnant women in Latin America.

KEYWORDS Antenatal diagnosis, prenatal diagnosis, antenatal screening, chromosomal aberrations, chromosomal breakpoints, pregnancy, Colombia, Costa Rica, Cuba, Mexico, Uruguay, Latin America

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.

OBJECTIVE 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.

KEYWORDS Antenatal diagnosis, prenatal diagnosis, antenatal screening, Down syndrome, aneuploidy, chromosomal mosaicism, genetic diseases, genetic services, cytogenetics, hereditary disease, medical genetics, Cuba