Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease.

Congenital anomalies (CA) affect 3-5% of newborns, representing the second-leading cause of infant mortality in Argentina. Multiple congenital anomalies (MCA) have a prevalence of 2.26/1000 births in newborns, while congenital heart diseases (CHD) are the most frequent CA with a prevalence of 4.06/1000 births. The aim of this study was to identify the genetic causes in Argentinian patients with MCA and isolated CHD. We recruited 366 patients (172 with MCA and 194 with isolated CHD) born between June 2015 and August 2019 at public hospitals. DNA from peripheral blood was obtained from all patients, while karyotyping was performed in patients with MCA. Samples from patients presenting conotruncal CHD or DiGeorge phenotype (n = 137) were studied using MLPA. Ninety-three samples were studied by array-CGH and 18 by targeted or exome next-generation sequencing (NGS). A total of 240 patients were successfully studied using at least one technique. Cytogenetic abnormalities were observed in 13 patients, while 18 had clinically relevant imbalances detected by array-CGH. After MLPA, 26 patients presented 22q11 deletions or duplications and one presented a TBX1 gene deletion. Following NGS analysis, 12 patients presented pathogenic or likely pathogenic genetic variants, five of them, found in KAT6B, SHH, MYH11, MYH7 and EP300 genes, are novel. Using an algorithm that combines molecular techniques with clinical and genetic assessment, we determined the genetic contribution in 27.5% of the analyzed patients.

Diprosopus: Systematic review and report of two cases.

BACKGROUND: Diprosopus is a subtype of symmetric conjoined twins with one head, facial duplication and a single trunk. Diprosopus is a very rare congenital anomaly. METHODS: This is a systematic review of published cases and the presentation of two new cases born in Argentina. We estimated the prevalence of conjoined twins and diprosopus using data from the National Network of Congenital Anomalies of Argentina (RENAC). RESULTS: The prevalence of conjoined twins in RENAC was 19 per 1,000,000 births (95% confidence interval, 12-29). Diprosopus prevalence was 2 per 1,000,000 births (95% confidence interval, 0.2-6.8). In the systematic review, we identified 31 diprosopus cases. The facial structures more frequently duplicated were nose and eyes. Most frequent associated anomalies were: anencephaly, duplication of cerebral hemispheres, craniorachischisis, oral clefts, spinal abnormalities, congenital heart defects, diaphragmatic hernia, thoracic and/or abdominal visceral laterality anomalies. One of the RENAC cases and three cases from the literature had another discordant nonmalformed twin. CONCLUSION: The conjoined twins prevalence was similar to other studies. The prevalence of diprosopus was higher. The etiology is still unknown. The presence of visceral laterality anomalies may indicate the link between diprosopus and the alteration or duplication of the primitive node in the perigastrulation period (12-15 days postfertilization). Pregnancies of more than two embryos may be a risk factor for diprosopus. Given the low prevalence of this defect, it would be useful to perform studies involving several surveillance systems and international consortiums. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:993-1007, 2016. © 2016 Wiley Periodicals, Inc.

Validación de tablas de la biometría fetal para su uso en Argentina y la importancia en la detección precoz de alteraciones del crecimiento fetal / Validation of fetal biometry tables for use in Argentina and the importance in the early detection of fetal growth disorders

INTRODUCCION La medición ecográfica de segmentos fetales permite establecer la edad gestacional y evaluar el crecimiento fetal. La biometría fetal es una herramienta para detectar desviaciones del crecimiento, malformaciones y diagnosticar algunos síndromes genéticos. Existen numerosas tablas de la biometría fetal y las más usadas fueron elaboradas en otros países. OBJETIVO Seleccionar las tablas de la biometría fetal más adecuadas para evaluar los fetos de nuestra población y proponer su uso unificado en todo el país. Mejorar la detección de las alteraciones del crecimiento fetal. MÉTODOS Diseño; Estudio observacional, de corte transversal, prospectivo. Durante 9 meses 65 ecografistas obtuvieron medidas del Diámetro Biparietal, Circunferencia Cefálica, Circunferencia Abdominal y Longitud Femoral. Las medidas fueron cargadas a una base de datos de una página web. Los valores obtenidos se compararon con tablas de autores clásicos como Hadlock o Chitty y con las de autores sudamericanos como Fescina y Lagos, y las de Aguirre (CENAGEM) utilizando Z-score. Material; Mujeres embarazadas no seleccionadas de distintos lugares del país. RESULTADOS Se obtuvieron medidas de los distintos segmentos fetales de un total de 2384 embarazadas y para cada semana de edad gestacional. Se comparó el efecto sobre la distribución de frecuencia de las curvas publicadas por los otros autores usando Z-score. Se calculó el impacto clínico de la selección de tablas por medio de distintas tasas en relación con las medidas obtenidas y las esperadas por fuera de los percentilos 5 y 95. Se usó el índice de Youden para establecer la mejor relación entre sensibilidad y especificidad. No se pudo establecer estas relaciones con los autores que no publicaron sus ecuaciones de ajuste para los desvíos estándar. DISCUSIÓN Las tablas de Aguirre y cols para los 4 segmentos son las que mejor ajustan al haber obtenido el mejor Índice de Youden. Estas tablas son las que se sugieren para su uso unificado en la población Argentina