Publication: Valor del estudio de las anomalías cromosómicas en fetos con cardiopatía congénita: factores de riesgo e importancia pronóstica
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2017-08-16
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Universidad Complutense de Madrid
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Abstract
Las CC son una de las malformaciones congénitas más frecuentes, constituyendo el 30- 40% de las todas las anomalías presentes al nacimiento. La trascendencia de estos defectos no radica únicamente su elevada prevalencia, sino también en su enorme repercusión sobre la morbi-mortalidad perinatal. El estudio de las malformaciones cardiacas en las últimas décadas ha permitido realizar notables progresos en el conocimiento de sus bases tanto anatómicas como fisiológicas. Aunque los estudios de recurrencia y riesgo de transmisión llevan a pensar que la mayor parte de las mismas (70-90%) tienen un origen multifactorial, se sabe que un 10-30% es posible identificar una alteración monogénica o una CRX responsable del origen del defecto cardiaco. El control genético del desarrollo cardiaco se encuentra regulado por una cascada de genes y sus productos derivados, relacionados entre sí a través de una vasta red de interacciones. Este aspecto y la participación de mecanismos epigenéticos hacen que una determinada alteración genética pueda condicionar el desarrollo de diferentes defectos cardiacos y que, del mismo modo, diferentes anomalías genotípicas puedan converger en la aparición de una misma CC. Es por ello que la presencia de CC y su tipo es variable en cada CRX al igual que la prevalencia de anomalías cromosómicas, la cual es diferente para cada defecto cardiaco. Además, aunque se han observado algunas relaciones preferenciales como la T21 en el CAV (77%) o la DEL 22q11 en la IAA (87%), en general es posible encontrar cualquier CRX en cada CC. Cuando la alteración genética responsable de la aparición de la CC afecta a genes que controlan procesos iniciales del desarrollo embrionario o cuando la cantidad de material genético afectado es amplia, como puede ser el caso de las CRX, no es infrecuente que la expresión fenotípica suela acompañarse de otras anomalías morfológicas. El desarrollo tecnológico y los avances en el diagnóstico prenatal así como la descripción de nuevos marcadores ecográficos de CRX y la progresiva implementación de programas de cribado han permitido mejorar con el tiempo las tasas de detección tanto de las anomalías congénitas como de las CRX. Por último, el pronóstico de las CC es diferente de unas entidades a otras. Este aspecto se encuentra claramente condicionado por el grado de complejidad del defecto cardiaco pero también por la participación de otros factores como la presencia de una CRX, de modo que se ha podido observar que la coexistencia de ambas situaciones contribuye a un empeoramiento significativo del pronóstico perinatal. Este aspecto es el que ha llevado tradicionalmente a recomendar de manera sistemática y rutinaria el estudio del cariotipo fetal ante el diagnóstico prenatal de una CC...
Congenital heart defects (CHD) are one of the most common congenital malformations, accounting for 30-40% of all abnormalities present at birth. The importance of these defects is related to this high prevalence, but also to the huge impact on perinatal outcome. The study of cardiac malformations in the last decades has allowed remarkable advances in understanding their anatomical and physiological basis. Studies of recurrence and risk of transmission have shown a multifactorial origin in most CHD (70-90%). However, it is possible to identify a monogenic disorder or a chromosomal abnormality (CA) in 10-30% of the defects. Genetic control of cardiac development is regulated by a cascade of genes and their derivatives which are integrated in a vast interaction network. This fact and the involvement of epigenetic mechanisms make that a particular CA may develop different CHD. Conversely, different CA can converge in the development of the same CHD. That is why the presence of CHD and its type is variable in each CA as well as the prevalence of chromosomal defects, which is different for each heart defect. Furthermore, although there have been some preferential relations as trisomy 21 in atrio-ventricular septal defect (AVSD) (77%) or microdeletion 22q11 in aortic arch interruption (87%), it is possible to find any CA in each CHD. When genetic disorder affects genes regulating early developmental processes or when the amount of genetic material is large, such as in CA, it is not unusual to find other morphological associated anomalies. Technological development, advances in prenatal diagnosis, description of new ultrasound chromosomal markers and progressive implementation of screening programs have improved detection rates of congenital anomalies and CA. Finally, prognosis of CHD is different for each group. This is clearly conditioned by the complexity of the heart defect but also by the participation of other factors such as the presence of a CA. It is well known that the coexistence of both situations contributes to a significant worsening of perinatal outcome. This is why fetal karyotyping has traditionally been recommended after prenatal diagnosis of CHD. Noninvasive prenatal diagnosis of aneuploidies has experienced a significant progress in recent years. However, invasive tests are mostly performed because of the limitations of these techniques. However, these tests are not risk-free and association of CHD and CA is not uniform in different cardiac defects. According to this, an individually prenatal counseling should be performed following the diagnosis of a CHD...
Congenital heart defects (CHD) are one of the most common congenital malformations, accounting for 30-40% of all abnormalities present at birth. The importance of these defects is related to this high prevalence, but also to the huge impact on perinatal outcome. The study of cardiac malformations in the last decades has allowed remarkable advances in understanding their anatomical and physiological basis. Studies of recurrence and risk of transmission have shown a multifactorial origin in most CHD (70-90%). However, it is possible to identify a monogenic disorder or a chromosomal abnormality (CA) in 10-30% of the defects. Genetic control of cardiac development is regulated by a cascade of genes and their derivatives which are integrated in a vast interaction network. This fact and the involvement of epigenetic mechanisms make that a particular CA may develop different CHD. Conversely, different CA can converge in the development of the same CHD. That is why the presence of CHD and its type is variable in each CA as well as the prevalence of chromosomal defects, which is different for each heart defect. Furthermore, although there have been some preferential relations as trisomy 21 in atrio-ventricular septal defect (AVSD) (77%) or microdeletion 22q11 in aortic arch interruption (87%), it is possible to find any CA in each CHD. When genetic disorder affects genes regulating early developmental processes or when the amount of genetic material is large, such as in CA, it is not unusual to find other morphological associated anomalies. Technological development, advances in prenatal diagnosis, description of new ultrasound chromosomal markers and progressive implementation of screening programs have improved detection rates of congenital anomalies and CA. Finally, prognosis of CHD is different for each group. This is clearly conditioned by the complexity of the heart defect but also by the participation of other factors such as the presence of a CA. It is well known that the coexistence of both situations contributes to a significant worsening of perinatal outcome. This is why fetal karyotyping has traditionally been recommended after prenatal diagnosis of CHD. Noninvasive prenatal diagnosis of aneuploidies has experienced a significant progress in recent years. However, invasive tests are mostly performed because of the limitations of these techniques. However, these tests are not risk-free and association of CHD and CA is not uniform in different cardiac defects. According to this, an individually prenatal counseling should be performed following the diagnosis of a CHD...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Obstetricia y Ginecología, leída el 25-01-2016