Antenatal Diagnosis of De Novo Balanced Structural Chromosome Aberrations in Latin America.

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.

Correlación cariotipo-fenotipo de síndrome deleción 9p: Enfoque de citogenética convencional y molecular / Karyotype-phenotype correlation in 9p deletion syndrome: conventional and molecular cytogenetic approach

La correlación cariotipo fenotipo en pacientes con aberraciones cromosómicas no balanceadas, constituye un conocimiento valioso en la práctica de la genética clínica, ya que la delineación clínica y las características dismórficas que los distinguen, orientan al genetista clínico a proponer un diagnóstico etiológico inicial, frente a la gran diversidad de síndromes genéticos a los que se enfrenta en su práctica diaria. Sin embargo, la mayoría de los reportes se realizan en edades pediátricas y no existen muchas publicaciones que proporcionen la oportunidad de apreciar los cambios que se producen en su fenotipo, ni las desviaciones del desarrollo que se pudieran presentar evolutivamente a través de su ciclo de vida, en aberraciones cromosómicas de muy baja frecuencia. El caso que se presenta, constituye un ejemplo de correlación fenotipo cariotipo evolutiva, que además tiene en cuenta las experiencias obtenidas por reportes de la aplicación de la citogenética molecular en casos de deleciones que involucran al brazo corto del cromosoma 9…(AU)