Prenatal genetic considerations in congenital ventriculomegaly and hydrocephalus.

BACKGROUND: Fetal ventriculomegaly (VM) is a frequent finding in prenatal ultrasound. Rather than a proper diagnosis, VM is a sonographic sign, making prenatal counseling a complex and challenging undertaking. VM can range from severe pathologic processes leading to severe neurodevelopmental delay to normal variants. DISCUSSION: A growing number of genetic conditions with different pathophysiological mechanisms, inheritance patterns, and long-term prognosis have been associated both to isolated and complex fetal VM. These include chromosomal abnormalities, copy number variants, and several single gene diseases. In this review, we describe some of the most common genetic conditions associated with fetal VM and provide a simplified diagnostic workflow for the clinician.

Uso de paneles multigénicos en el estudio de cáncer de mama hereditario / Use of multigenic panels in the study of hereditary breast cancer

El cáncer de mama es el tipo de cáncer más frecuente y la primera causa de mortalidad asociada a cáncer en la mujer. Si bien la mayoría de los casos son esporádicos, 5 a 10% de los mismos son causados por mutaciones germinales en genes de susceptibilidad al cáncer de alta y moderada penetrancia. Dichos genes se asocian a un incremento del riesgo individual de desarrollar cáncer de 5 veces y de 2-5 veces, respectivamente. brca1 y 2 fueron los primeros genes de susceptibilidad asociados a cáncer de mama en ser identificados, y se encuentran dentro de los estudios ya aceptados por la comunidad médica y social. Mutaciones en estos genes no solo aumentan el riesgo de desarrollar cáncer de mama en comparación con la población general, sino que también se asocian a un incremento en el riesgo de desarrollar otros tipos de cáncer: ovario, páncreas, melanoma y, en hombres, próstata

A snapshot of current genetic testing practice in Lynch syndrome: The results of a representative survey of 33 Latin American existing centres/registries.

We aimed to assess the current genetics practice to manage patients with Lynch syndrome (LS) across Latin America. A Latin American LS survey was sent out to 52 centres/registries, comprising a total of 12 countries from the region. Overall, 33 centres completed the survey, of which the oldest LS registry was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Jose (Costa Rica). In total, 87% (26/30) of the participating centres/registries belonging to the nine countries are performing genetic testing. Overall, 1352 suspected families were sequenced. Pathogenic variants were identified in 34% of the families, with slightly differing distribution of variants between females and males. Path_MLH1 variants were identified in 39% of females and 50% of males (p = 0.023), while path_MSH2 were identified in 37% of females and males, followed by path_PMS2 in 11% of females and 8% of males, path_MSH6 in 13% of females and 3% of males (p < 0.001) and path_EPCAM in 0.3% of females and 2% of males. In Latin America, 9 of 12 (75%) participating countries had implemented healthcare for LS. LS screening is inconsistently applied within Latin America healthcare systems because of structural differences in the healthcare systems between the countries.

Fetal cardiac abnormalities: Genetic etiologies to be considered.

Congenital heart diseases are a common prenatal finding. The prenatal identification of an associated genetic syndrome or a major extracardiac anomaly helps to understand the etiopathogenic diagnosis. Besides, it also assesses the prognosis, management, and familial recurrence risk while strongly influences parental decision to choose termination of pregnancy or postnatal care. This review article describes the most common genetic diagnoses associated with a prenatal finding of a congenital heart disease and a suggested diagnostic process.

Cost-effectiveness of cytogenetic evaluation of products of conception by chorionic villus sampling in recurrent miscarriage.

OBJECTIVE: To compare the cost-effectiveness of performing chorionic villus sampling (CVS) of products of conception (POC) in the evaluation of recurrent miscarriage versus standard evidence-based work-up (EBW) of the couple. MATERIAL AND METHODS: A decision-analytic model was performed in couples with a third miscarriage. Three strategies were considered: (1) the standard EBW of all the patients, comprising parental karyotype, uterine cavity assessment and antiphospholipid antibodies; (2) performing a CVS of POC and a standard karyotype, and if euploid, follow with EBW; and (3) performing a CVS of POC and an arrayCGH and, if normal, follow with EBW. Estimated cost and diagnostic yield of each strategy was analysed. Sensitivity analysis and threshold cost were considered. RESULTS: The expected cost-effectiveness of CVS and karyotype of POC in recurrent miscarriage was: $US769.79 versus $US 1361.8 for the standard EBW of the couple. When stratified by maternal age the results remained cost-effective for this strategy. The arrayCGH strategy has a higher diagnostic yield, but still expensive in our setting to be considered cost-effective. CONCLUSIONS: Chorionic villus sampling and karyotype analysis of products of conception in a third miscarriage proved a more cost-effective strategy than standard EBW of the couple. © 2017 John Wiley & Sons, Ltd.

Prenatal screening for chromosome abnormalities in a region with no access to termination of pregnancy.

OBJECTIVE: To analyze the different variables that affect couples' decision-making about prenatal screening of chromosome abnormalities in a population with limited access to prenatal diagnosis and no legal termination of pregnancy (TOP). METHODS: From February through August 2004, 79 couples who requested for prenatal screening at centers from Argentina and Uruguay participated in a study. A cross-sectional survey was administered to assess attitudes toward prenatal screening, the decision-making process, and knowledge and attitudes toward TOP. RESULTS: Mean maternal age was 32.8 +/- 0.4 years. Among the couples, 88.61% knew that TOP due to fetal anomalies is not legal in their countries. When asked about the possibility of TOP in case of a serious fetal anomaly, 53% would contemplate this option. CONCLUSION: Prenatal screening is a common practice worldwide. However, unlike most developed countries, our region has a limited access to prenatal diagnosis and no legal TOP. Those couples who stated that 'reassurance about fetal well-being' was the most important reason to perform prenatal screening had more positive attitudes toward TOP than those who considered this screening important 'to be better prepared to receive the baby'. Our findings can be used to inform and revise current health-care policies.