ABSTRACT
La pentalogía de Cantrell es un raro espectro de malformaciones congénitas que consiste en cinco defectos: defecto de la línea media de la pared abdominal supraumbilical, defecto de la parte inferior del esternón, agenesia de la porción anterior del diafragma con ausencia de la porción diafragmática del pericardio y uno o varios defectos congénitos intracardíacos; sin embargo, los signos distintivos del síndrome son: onfalocele asociado con ectopia cordis. Es un trastorno con baja frecuencia general, con una incidencia estimada de 5,5-7,9 por millón de nacidos vivos. En Cuba, desde 1985 en que comenzó el Registro Cubano de Malformaciones Congénitas, solo aparecen inscriptos 10 casos y solo dos han sido descritos en la literatura.Objetivo: Describir las características clínicas de un caso con una de las formas incompletas de la pentalogía de Cantrel.Presentación de caso: Mujer de 39 años atendida en la consulta de Genética del Centro Provincial de Genética de Mayabeque como parte del seguimiento establecido en la metodología del Programa de Diagnóstico, Manejo y Prevención de Enfermedades Genéticas y Defectos Congénitos. Luego de realizar los exámenes correspondientes se le diagnostica al feto una de las formas incompletas de pentalogía de Cantrell (ectopia cordis, gastrosquisis y onfalocele).Conclusiones: Se consideró conveniente la divulgación de este caso dada la baja frecuencia del trastorno y por ser el primero diagnosticado en la provincia Mayabeque...(AU)
Subject(s)
Humans , Male , Female , Genetics/ethics , Pentalogy of Cantrell/genetics , Ectopia Cordis/genetics , Congenital Abnormalities/genetics , Cuba/epidemiologyABSTRACT
Midline defects account for approximately 5% of congenital abnormalities observed at birth. However, the molecular mechanisms underlying the formation of the ventral body wall are not well understood. Recent studies linked mutations in Porcupine-an O-acetyl transferase mediating Wnt ligand acylation-with defects in the thoracic body wall. We hypothesized that anomalous Wnt signaling is involved in the pathogenesis of defective closure of the thoracic body wall. We generated a mouse model wherein Wntless (Wls), which encodes a cargo receptor mediating secretion of Wnt ligands, was conditionally deleted from the developing mesenchyme using Dermo1Cre mice. Wls(f/f);Dermo1(Cre/+) embryos died during mid-gestation. At E13.5, skeletal defects were observed in the forelimbs, jaw, and rib cage. At E14.5, midline defects in the thoracic body wall began to emerge: the sternum failed to fuse and the heart protruded through the body wall at the midline (ectopia cordis). To determine the molecular mechanism underlying the phenotype observed in Wls(f/f);Dermo1(Cre/+) embryos, we tested whether Wnt/ß-catenin signaling was operative in developing the embryonic ventral body wall using Axin2(LacZ) and BatGal reporter mice. While Wnt/ß-catenin signaling activity was observed at the midline of the ventral body wall before sternal fusion, this pattern of activity was altered and scattered throughout the body wall after mesenchymal deletion of Wls. Mesenchymal cell migration was disrupted in Wls(f/f);Dermo1(Cre/+) thoracic body wall partially due to anomalous ß-catenin independent Wnt signaling as determined by in vitro assays. Deletion of Lrp5 and Lrp6 receptors, which mediate Wnt/ß-catenin signaling in the mesenchyme, partially recapitulated the phenotype observed in the chest midline of Wls(f/f);Dermo1(Cre/+) embryos supporting a role for Wnt/ß-catenin signaling activity in the normal formation of the ventral body wall mesenchyme. We conclude that Wls-mediated secretion of Wnt ligands from the developing ventral body wall mesenchyme plays a critical role in fusion of the sternum and closure of the secondary body wall. Thus, impaired Wls activity in the ventral body wall mesenchyme is a mechanism underlying ectopia cordis and unfused sternum.
Subject(s)
Intracellular Signaling Peptides and Proteins/genetics , Mesoderm/embryology , Receptors, G-Protein-Coupled/genetics , Sternum/embryology , Thoracic Cavity/embryology , Wnt Proteins/genetics , Acyltransferases , Animals , Axin Protein/genetics , Cell Movement/genetics , Cell Proliferation , Cells, Cultured , Ectopia Cordis/genetics , Gene Expression Regulation, Developmental , Low Density Lipoprotein Receptor-Related Protein-5/genetics , Low Density Lipoprotein Receptor-Related Protein-6/genetics , Membrane Proteins/genetics , Mesoderm/metabolism , Mice , Mice, Knockout , Neural Tube Defects/genetics , Wnt Signaling Pathway/genetics , beta Catenin/geneticsABSTRACT
Trata-se de doença congênita, descrita por Cantrell, em 1958, caracterizada por ectopia cordis e malformações da parede abdominal. A prevalência é um em cada 65.000 nascidos vivos. Existem, aproximadamente, 900 casos descritos. O prognóstico é reservado, depende do grau de malformação intracardíaca e malformações associadas, além do grau de exposição do coração. A maioria das crianças falece nas primeiras horas de vida. A criança deste relato apresenta forma completa da síndrome de Cantrell. Infelizmente, a correção cirúrgica da onfalocele não pôde ser realizada, devido ao trabalho de parto precoce e morte da criança.
Subject(s)
Animals , Female , Infant, Newborn , Heart Defects, Congenital/complications , Ectopia Cordis/genetics , Abdominal Wall/abnormalitiesABSTRACT
Ectopia cordis and mosaic trisomy 16 are two rare fetal anomalies, which have not been reported in association. We report a case of an isolated ectopia cordis at 11(+3) weeks. Subsequent embryological examination confirmed thoracic ectopia cordis with normal heart structure and array comparative genomic hybridization of fetal tissue detected trisomy 16 mosaicism.
Subject(s)
Ectopia Cordis/diagnostic imaging , Ultrasonography, Prenatal/methods , Abortion, Eugenic , Adult , Chromosomes, Human, Pair 16/genetics , Ectopia Cordis/genetics , Female , Humans , Mosaicism , Pregnancy , Trisomy/diagnosis , Trisomy/genetics , Young AdultABSTRACT
Se presentó un caso, con examen sonográfico, en el primer trimestre del embarazo en el que se informó una translucencia nucal de 5mm para 11,4 semanas. En un estudio realizado a las 12 semanas se visualizó ectopia cordis y onfalocele que son defectos que hicieron sospechar el diagnóstico de una Pentalogía de Cantrell asociada a una espina bífida que se observó a las 15 semanas. Se realizó el estudio citogenético fetal, con resultado normal 46, XY y previo asesoramiento genético la pareja decidió la interrupción del embarazo. El estudio anatomopatológico confirmó una pentalogía completa. Este es un síndrome de muy rara ocurrencia. Por la precocidad e integralidad en el diagnóstico nos propusimos reportar este caso que evidencia la importancia del estudio ecográfico en el primer trimestre del embarazo, posibilitando un adecuado asesoramiento genético desde las etapas iniciales orientado a diferentes síndromes que, como en este caso, pudieran ser poco frecuentes en la literatura mundial (AU)