Diagnostico prenatal en Sindrome de Cornelia de Lange a propósito de 2 casos / Prenatal diagnosis in Cornelia de Lange syndrome in 2 cases

RESUMEN El Síndrome de Cornelia de Lange (SCdL) es un trastorno hereditario del desarrollo con transmisión dominante, aunque la mayoría de los casos son esporádicos. La prevalencia es variable oscilando entre 1/10.000-1/100.000 nacimientos. Se caracteriza por un fenotipo facial distintivo, anomalías en las extremidades superiores y retraso del crecimiento y psicomotor. El diagnóstico prenatal de este síndrome está limitado a la detección de anomalías mayores, ya que los rasgos fenotípicos distintivos del mismo no son fácilmente detectables. Suele cursar con aumento de la translucencia nucal, higroma quístico y valores de PAPP-A bajos en el primer trimestre de la gestación; retraso del crecimiento intrauterino, retromicrognatia, anomalías con grado variable de severidad de las extremidades superiores y otras anomalías cardiovasculares, gastrointestinales o genitourinarias que condicionan el pronóstico fetal. Se presentan los hallazgos ecográficos de dos casos con sospecha de afectación por el SCdL, y la correlación entre los mismos y los hallazgos en la necropsia. Al establecer la sospecha diagnóstica de forma retrospectiva, en los casos presentados no fue posible estudiar la presencia de mutaciones genéticas asociadas con el SCdL. A pesar de los avances en el diagnóstico genético de este síndrome, la base genética del mismo es todavía desconocida en alrededor del 30% de los pacientes, lo que sugiere la contribución de otros genes y/o factores ambientales en su etiología.

ABSTRACT Cornelia de Lange Syndrome (CdLS) is an hereditary developmental disorder with dominant condition, although most cases are sporadic. The prevalence is variable ranging from 1/10,000 to 1/100,000 live births. It is characterized by a distinct facial phenotype, upper limb abnormalities, growth retardation and severe mental retardation. Prenatal diagnosis of this syndrome is limited to detecting major abnormalities, since characteristic facial features aren't easily detectable. Is usually associated with increased nuchal translucency, cystic hygroma and low PAPP- A levels in first trimester of pregnancy; intrauterine growth retardation, retromicrognathia, anomalies with varying degrees of severity of upper limbs and other cardiovascular, gastrointestinal or genitourinary abnormalities that affect fetal prognosis. The sonographic findings of two cases with suspected involvement by CdLS, and the correlation between them and necropsy findings are presented. Since the suspected diagnosis was established retrospectively in the presented cases, it wasn't possible to study the association with CdLS gene mutations. Despite advances in genetic diagnosis of this syndrome, the genetic basis of it still unknown in about 30% of patients, suggesting the contribution of other genes and/or environmental factors in its etiology.

Evaluation of acute skin toxicity in breast radiotherapy with a new quantitative approach.

BACKGROUND AND PURPOSE: Current criteria to evaluate acute radiodermatitis are highly subjective so quantification of physiological parameters is needed. We describe a non-invasive method of assessing skin microcirculation in breast cancer patients treated with hypofractionated radiotherapy and correlate them with the CTCAE scale. METHODS: Prospective study of 63 patients where blood flow was measured with real-time laser Doppler flowmetry (LDF) at baseline, weekly, and 3-months post-radiotherapy. Skin toxicity was assessed with the microcirculation index (MCI), a novel index based on blood flow parameters obtained via LDF. RESULTS: MCI was positively correlated (R=0.647; p<0.001) with the dose. Changes in MCI from baseline to the end of radiotherapy and at 3-months post-radiotherapy were significant (p<0.001). All CTCAE groups experienced a significant increase in MCI values from baseline to end of radiotherapy (p<0.001 for CTCAE grades 0 and 1; and p=0.028 for the grade 2 group). Significant differences in MCI values were observed among CTCAE groups at the end of radiotherapy (p=0.016). CONCLUSIONS: LDF is an accurate and objective measure of changes in blood flow. The comparison with the CTCAE shows the limitations of this subjective way of classifying patients. LDF is the first step for future studies of radiodermatitis treatments and prevention.

Is cognitive impairment in cirrhotic patients due to increased peroxynitrite and oxidative stress?

Cirrhotic patients may suffer minimal hepatic encephalopathy (MHE), with mild cognitive impairment. 3-Nitro-tyrosine levels are a good biomarker for diagnosis of the cognitive impairment and MHE in cirrhotic patients. This suggests that oxidative stress could be involved in the induction of cognitive and motor alterations in MHE. We have observed that patients with MHE show increased oxidative stress in blood compared with cirrhotic patients without MHE, with increased lipid peroxidation, DNA oxidation, protein carbonylation, 3-nitrotyrosine, oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio, and GSH levels. The activities of antioxidant enzymes are enhanced in erythrocytes and mononuclear cells from patients with and without MHE compared with control subjects. Only glutathione peroxidase activity was increased in MHE patients compared with patients without MHE. Oxidative stress markers in blood, especially GSSG/GSH ratio, GSH, malondialdehyde, and 3-nitrotyrosine, correlate with deficits in attention and motor coordination. The increase in antioxidant activities in patients would be an adaptive mechanism to cope with enhanced oxidative stress, although it is not effective enough to normalize it. Our observations lead to the hypothesis that oxidative stress and increased peroxynitrite formation would mediate the synergistic effects of hyperammonemia and inflammation on cognitive and motor impairment in MHE.

Tumor bed segmentation: first step for partial breast irradiation.

INTRODUCTION: In breast IMRT simultaneous integrated boost (SIB) treatment and accelerated partial breast irradiation (APBI), proper delineation of the tumor bed is necessary. Conservative oncoplastic surgery causes changes in peritumoral breast tissue that complicates locating the site of the tumor. Nevertheless, there are still centers that do not use surgical clips to delineate the site. This study aims to show how the lack of clips affects the techniques of SIB and APBI in terms of dose distribution and safety margins in the tumor bed. MATERIALS AND METHODS: On 30 patients, the defining of the tumor bed obtained from the pre-surgery CT scan to that outlined on the basis of clips on the post-surgery CT was compared. Tumor bed deviation from the original tumor site was quantified. In addition, the margins to the original tumor site necessary to guarantee the coverage of the tumor bed were calculated. RESULTS: Variations were detected in the distances between geometric centers of the PTV (minimum 0.5-maximum 3 cm). The maximum margin necessary to include the entire tumor bed was 4.5 cm. Lesions located in the upper outer quadrant required the widest margins. If margins are not added, the tumor bed volume defined with clips will be underdosed. CONCLUSIONS: The definition of the tumor bed based on studies before surgery does not have the necessary accuracy. Clips need to be placed in the surgical bed to identify the changes occurring after the restorative mammoplasty. Without clips, SIB and APBI are not safe.

Situs ambiguous in a schoolchild.

We report the case of a 9-year-old child with asthma, atopic dermatitis and allergic rhinoconjunctivitis due to house dust mites, in whom a routine chest x-ray identified by chance abnormal organ position, such as the stomach located on the right side. Abdominal ultrasonography indicated a centralised liver, with polysplenia on the right side and an inferior cava vein located to the left of the aorta with no interruption. Ultrasonography did not show heart defects. Magnetic resonance imaging (MRI) of the abdomen was performed that showed a short pancreas, with no neck, body and tail in it, and a left inferior vena cava with normal outlet of the renal veins, and absence of the intrahepatic part of the inferior vena cava, that was replaced by the left hemiazygos vein. Spinal cord MRI revealed dorsal syringomelia. In view of the results obtained, the diagnosis of situs ambiguous was established.

Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection.

Aicardi-Goutières syndrome (AGS) is an autosomal recessive neurological disorder, the clinical and immunological features of which parallel those of congenital viral infection. Here we define the composition of the human ribonuclease H2 enzyme complex and show that AGS can result from mutations in the genes encoding any one of its three subunits. Our findings demonstrate a role for ribonuclease H in human neurological disease and suggest an unanticipated relationship between ribonuclease H2 and the antiviral immune response that warrants further investigation.

Asociación entre la incidencia de alteraciones tomográficas pulmonares y el volumen pulmonar irradiado en pacientes con cáncer de mama / Relation between incidence of tomographic changes and radiated volume in the lungs of breast cancer patients

Objetivo: Determinar mediante tomografía pulmonar de alta resolución, la incidencia de alteraciones producidas por la irradiación del cáncer de mama en el pulmón y su relación con el volumen pulmonar irradiado. Material y métodos: Estudio prospectivo de 59 pacientes con cáncer de mama sometidas a radioterapia complementaria. Se practicó tomografía pulmonar de alta resolución a los tres y nueve meses de finalizar la radioterapia. Se analizó la incidencia de signos de neumonitis y fibrosis por radiación, y se estudió su relación con el volumen pulmonar irradiado. Resultados: El desarrollo del signo más frecuente de neumonitis (consolidaciones parcheadas contenidas en el pulmón irradiado pero no limitadas a la forma del campo de radiación) y de los más frecuentes de fibrosis (pérdida de volumen y desarrollo de opacidades lineales abigarradas), se asociaron significativamente al volumen y porcentaje de pulmón incluido en el campo de tratamiento, de forma que en las pacientes que no los presentaron, el porcentaje y el volumen pulmonar irradiado fueron muy inferiores al de las pacientes que sí los desarrollaron. La edad y la quimioterapia no se asociaron significativamente a la presencia de los signos de neumonitis y fibrosis por radiación. Todas las pacientes permanecieron asintomáticas. Conclusiones: Es necesario realizar una minuciosa simulación de los tratamientos y cuantificar en cada paciente el volumen pulmonar incluido en el campo de irradiación, y es recomendable llevar a cabo un seguimiento de la función pulmonar de aquellas pacientes en las que no sea factible la irradiación de un volumen de pulmón inferior a 150 cm3 o un porcentaje del volumen pulmonar inferior al 12 por ciento (AU)