ABSTRACT 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.

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.

SUMMARY: A total number of 1 191 prenatal chromosomal studies were carried out from October 1996 to April 1999 in the City of Havana. The most frequent reason for this was the maternal age (70.36 % of total cases). 47 fetuses with chromosomal abnormalities incluiding 17 Down's syndrome cases, 10 structural chromosomal rearranements and 13 mosaique, among others, were detected. T1though the highest number of positive results were found in old pregnant women, the highest risk groups were those in which one parent was a carrier of balanced chromosomal rearrangement and the fetal malformations detected by ultrasound were often associated to chromosomal diseases. All the couples whose test results indicated fetuses with chromosomal imbalance opted for abortion after they received relevant information in specialized visits, following the principle of non-directive genetic counselling.

Durante el período comprendido desde octubre de 1996 hasta abril de 1999 se realizaron un total de 1 191 estudios cromosómicos prenatales. La indicación más frecuente fue la avanzada edad materna (70,36 % del total de casos). Se diagnosticaron 47 fetos con anomalías cromosómicas, incluyendo 17 casos con síndrome de Down, 10 con reordenamientos cromosómicos estructurales y 13 mosaicos, entre otros. Aunque la mayor cantidad de resultados positivos se encontraron en el grupo de gestantes con avanzada edad, los grupos de mayor riesgo fueron los que se estudiaron por ser un padre portador de reordenamiento cromosómico balanceado y también por hallazgos ultrasonográficos de malformaciones fetales frecuentemente asociadas con enfermedades cromosómicas. La totalidad de parejas en las que se encontraron resultados de fetos con desbalances cromosómicos optaron por realizarse interrupciones de los embarazos, después de recibir la información correspondiente en consultas especializadas, siguiendo el principio del asesoramiento genético no directivo.

A patient with a reciprocal translocation between the long arms of chromosomes 13 and 18, which was apparently balanced, was prenatally detected. The karyotipe of both parents in the peripheral blood was normal and they decided no to run the risk of having an affected child. In the analysis of corroboration of the prenatal diagnosis that was made with fetal tissue, mosaicism was observed on appearing the same prenatally verified translocation in the skin culture and a normal chromosomic complement 46,XX in the fetal blood culture. Due to the unusual character of this mosaicism, it is recommended to have into account cases like this is in the genetic counseling consultations.

Se detecta prenatalmente un paciente con una translocación recíproca entre los brazos largos de los cromosomas 13 y 18, que aparentemente era balanceada. El cariotipo de ambos padres en la sangre periférica fue normal y deciden no correr el riesgo de tener un niño afectado. En el análisis de corroboración del diagnóstico prenatal, que se realizó en el tejido fetal, se observó un mosaicismo, al aparecer la misma translocación verificada prenatalmente en el cultivo de piel y un complemento cromosómico normal 46,XX en el cultivo de sangre fetal. Por lo inusual de este mosaicismo se recomienda tener en cuenta casos como éste en las consultas de asesoramiento genético.