Higroma quístico retronucal como marcador de anomalías cromosómicas en el primer trimestre de la gestación - Actualización

Objetivo. Evaluar la asociación del higroma quístico retronucal (HQR) y anomalías cromosómicas fetales. Métodos. Estudio observacional retrospectivo de 323 fetos del primer trimestre con riesgo para anomalías cromosómicas diagnosticados por ecografía entre las 11 y 13,6 semanas. Resultados. De 323 fetos con riesgo para anomalías cromosómicas, se encontró 132 casos de anomalías cromosómicas (40,9%). Se identificaron 145 casos de HQR; en 64 (56,6%) se realizó biopsia de vellosidades coriales y en 81 (43,5%) amniocentesis, hallándose cariotipo anómalo en 82 (56,6%). De 88 fetos con HQR aislado, 33 casos (37,5%) tuvieron alguna anomalía cromosómica; en 58 fetos con HQR asociado a otros hallazgos anormales, se encontró que en 43 fetos (74,1%) hubo anomalías cromosómicas, y de ellos 24 (41,4%) tenían onda de flujo (OVF) anormal del ductus venoso, 17 (29,3%) tenían edema generalizado, 8 casos (13,8%) con cardiopatía, 7 (12,1%) ausencia del hueso nasal. Los valores predictivos del HQR fueron: sensibilidad (S) 62,1%, especificidad (E) 67%, valor predictivo positivo (VPP) 56,6%, valor predictivo negativo (VPN) 71,9%, p<0,001, OR: 3,3. El HQR asociado a otros hallazgos anormales, tuvo los siguientes valores predictivos: S 52,4%, E 76,2%, VPP 76,2%, OR: 3,5, LR+: 2,2, p<0,000. El edema generalizado y el ductus venoso anormal tuvieron los valores predictivos más altos: VPP 88,2% y 83,3%, respectivamente. Las anomalías cromosómicas encontradas con mayor frecuencia fueron: T21 (53,7%), monosomía X (18,3%), T18 (15,9%), T13 (6,1%). Conclusiones. El higroma quístico retronucal es un marcador de riesgo con alto valor predictivo para anomalías cromosómicas, siendo mayor cuando está asociado a otros hallazgos ecográficos anormales. La identificación ecográfica del HQR en el tamizaje prenatal del primer trimestre debería ser indicación para recomendar una prueba diagnóstica para anomalías cromosómicas.

Objective: To evaluate the association of retronucal cystic hygroma (RCH) and fetal chromosomal abnormalities. Methods: Retrospective observational study of 323 first trimester fetuses at risk for chromosomal abnormalities diagnosed by ultrasound between 11 and 13.6 weeks. Results: Of 323 fetuses at risk for chromosomal abnormalities, 132 cases of chromosomal abnormalities were found (40.9%). A total of 145 cases of RCH were identified; chorionic villus biopsy was performed in 64 (56.6%) and amniocentesis in 81 (43.5%); an abnormal karyotype was found in 82 (56.6%). Of 88 fetuses with isolated RCH, 33 (37.5%) had some chromosomal abnormality. In 58 fetuses with RCH associated with other abnormal findings, chromosomal abnormalities were found in 43 fetuses (74.1%) and of these 24 (41.4%) had abnormal ductus venosus flow wave (DVF), 17 (29.3%) had generalized edema, 8 cases (13.8%) with cardiopathy, 7 (12,1%) with absent nasal bone. The predictive values of RCH were sensitivity (S) 62.1%, specificity (Sp) 67%, positive predictive value (PPV) 56.6%, negative predictive value (NPV) 71.9%, p<0.001, OR: 3.3. RCH associated with other abnormal findings were S 52.4%, Sp 76.2%, PPV 76.2%, OR: 3.5, LR+: 2.2, p<0.000. Generalized edema and abnormal ductus venosus had the highest predictive values: PPV 88.2% and 83.3%, respectively. The most frequently found chromosomal abnormalities were T21 (53.7%), monosomy X (18.3%), T18 (15.9%), T13 (6.1%). Conclusions: Retronucal cystic hygroma is a risk marker with high predictive value for chromosomal abnormalities, being higher when associated with other abnormal ultrasound findings. Ultrasonographic identification of RCH in first trimester prenatal screening should be an indication to recommend diagnostic testing for chromosomal abnormalities.

Rubinstein-Taybi syndrome in diverse populations.

Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant disorder, caused by loss-of-function variants in CREBBP or EP300. Affected individuals present with distinctive craniofacial features, broad thumbs and/or halluces, and intellectual disability. RSTS phenotype has been well characterized in individuals of European descent but not in other populations. In this study, individuals from diverse populations with RSTS were assessed by clinical examination and facial analysis technology. Clinical data of 38 individuals from 14 different countries were analyzed. The median age was 7 years (age range: 7 months to 47 years), and 63% were females. The most common phenotypic features in all population groups included broad thumbs and/or halluces in 97%, convex nasal ridge in 94%, and arched eyebrows in 92%. Face images of 87 individuals with RSTS (age range: 2 months to 47 years) were collected for evaluation using facial analysis technology. We compared images from 82 individuals with RSTS against 82 age- and sex-matched controls and obtained an area under the receiver operating characteristic curve (AUC) of 0.99 (p < .001), demonstrating excellent discrimination efficacy. The discrimination was, however, poor in the African group (AUC: 0.79; p = .145). Individuals with EP300 variants were more effectively discriminated (AUC: 0.95) compared with those with CREBBP variants (AUC: 0.93). This study shows that clinical examination combined with facial analysis technology may enable earlier and improved diagnosis of RSTS in diverse populations.

Acute liver failure in neonates with undiagnosed hereditary fructose intolerance due to exposure from widely available infant formulas.

Hereditary fructose intolerance (HFI) is an autosomal recessive disorder caused by aldolase B (ALDOB) deficiency resulting in an inability to metabolize fructose. The toxic accumulation of intermediate fructose-1-phosphate causes multiple metabolic disturbances, including postprandial hypoglycemia, lactic acidosis, electrolyte disturbance, and liver/kidney dysfunction. The clinical presentation varies depending on the age of exposure and the load of fructose. Some common infant formulas contain fructose in various forms, such as sucrose, a disaccharide of fructose and glucose. Exposure to formula containing fructogenic compounds is an important, but often overlooked trigger for severe metabolic disturbances in HFI. Here we report four neonates with undiagnosed HFI, all caused by the common, homozygous mutation c.448G>C (p.A150P) in ALDOB, who developed life-threatening acute liver failure due to fructose-containing formulas. These cases underscore the importance of dietary history and consideration of HFI in cases of neonatal or infantile acute liver failure for prompt diagnosis and treatment of HFI.

Preeclampsia: genes involucrados en mecanismos inflamatorios y vasculares / Preeclampsia: genes involved in inflammatory and vascular mechanisms

Esta revisión describe a los genes involucrados en los procesos inmunes y angiogénicos necesarios para la formación de la placenta, y cómo alteraciones en el fino equilibrio en el que están puede predisponer a la preeclampsia.

This review describes the genes involved in the immune and angiogenic processes that lead to normal placenta development and vascularity. Any change in this fragile equilibrium may predispose to preeclampsia.

Diagnóstico prenatal de anomalías cromosómicas: Examen prenatal no invasivo / Prenatal diagnosis of chromosome abnormalities: Noninvasive prenatal testing

El examen prenatal no invasivo es un método de tamizaje para encontrar a aquellas gestantes que tienen un riesgo de aneuploidía alto, específicamente para las trisomías 21, 18 y 13, y anomalías del cromosoma X. Requiere de una muestra de sangre periférica materna, en la que se analiza el ADN fetal libre circulante. En esta revisión detallamos los beneficios, desventajas e indicaciones del estudio.

Non-invasive prenatal test (NIPT) is a screening method that identifies pregnant women with a high aneuploidy risk, specifically for trisomy 21, 18, 13, and chromosome X anomalies. NIPT analyzes free fetal DNA found in maternal blood. In this review, we describe the benefits, disadvantages and study indications.

Germ cell tumour of the trachea.

A 28-year-old man presented with stridor and dyspnoea. Imaging showed a tracheal mass with severe narrowing of the subglottic airway. Histopathology was consistent with non-seminomatous germ cell tumour. The patient underwent cricotracheal resection and reconstruction of the trachea with tracheostomy. Subsequent positron emission tomography demonstrated new right upper lobe nodules. Postoperative chemotherapy was initiated using the VIP regimen (etoposide, ifosfamide and cisplatin). After four cycles of chemotherapy, CT of the thorax showed interval resolution of most of the pulmonary nodules. Thoracoscopy with right upper and lower lobe wedge resections was performed to remove the residual disease. The patient is currently disease-free and undergoing continued surveillance to assess for clinical, biochemical or radiographical evidence of disease recurrence.

CURB-65 and SMRT-CO in the prediction of early transfers to the intensive care unit among patients with community-acquired pneumonia initially admitted to a general ward.

BACKGROUND: No study has assessed the ability of pneumonia severity scores to identify the risk for early intensive care unit (ICU) transfer in patients with community-acquired pneumonia (CAP) admitted to general wards (GW). We aimed to compare the ability of CURB-65 (confusion, urea level, respiratory rate, blood pressure, and age ≥65 years) and SMRT-CO (systolic blood pressure, multilobar chest radiography involvement, respiratory rate, tachycardia, confusion, and oxygenation) scores to predict early ICU transfers in these patients. DESIGN: Retrospective, case-control study. Cases were defined as patients admitted to GW with CAP that required ICU transfer within 48 hours. Controls were defined as patients admitted to GW with CAP that did not require ICU transfer. CURB-65 and SMRT-CO scores were calculated on presentation to emergency department (ED), and upon admission to GW. Composite scores were calculated combining data from ED and GW. Sensitivities, specificities, likelihood ratios, and areas-under-the-curve (AUC) were calculated for each score. RESULTS: From 2003 to 2009, 115 cases and 345 controls were identified. Both groups had similar baseline characteristics. Composite scores combining data from ED and GW had better sensitivity and AUC than scores calculated only with ED or GW data (P < 0.001). A composite SMRT-CO score ≥2 had 76.5% (95% CI, 67.7 to 83.9) sensitivity, 67.5% (95% CI, 62.3 to 72.4) specificity, and 0.81 (95% CI, 0.77 to 0.85) AUC. A composite CURB-65 score ≥3 had 36.5% (95% CI, 27.7 to 46.0) sensitivity, 86.3% (95% CI, 82.3 to 89.8) specificity, and 0.66 (95% CI, 0.60 to 0.72) AUC to predict early ICU transfers. Composite SMRT-CO had higher sensitivity and AUC (P < 0.001) than composite CURB-65. CONCLUSIONS: Composite SMRT-CO had a better combination of sensitivity and specificity than CURB-65 for predicting early ICU transfers. Prospective studies to confirm our findings are needed.