RESUMEN
OBJECTIVES: Conotruncal malformations (CTMs) are a major feature of 22q11 microdeletion (22qdel). The prevalence of 22qdel in fetuses harboring these defects is unknown. We assessed the prevalence of 22qdel in a population of fetuses with conotruncal cardiac defects. STUDY DESIGN: Consecutive fetuses (n = 261) with a CTM and a normal karyotype were included in the study. All fetuses were screened for 22qdel by means of fluorescent in situ hybridization. RESULTS: A 22qdel was found in 54 fetuses (20.7%). The proportion of 22qdel for each CTM was: tetralogy of Fallot (14/100), pulmonary atresia with ventricular septal defect (11/61), tetralogy of Fallot with absent pulmonary valves (6/16), interrupted aortic arch (10/22), truncus arteriosus (9/29), and complex transpositions of the great arteries (4/33). Additional vascular anomalies were present in 75%. Typical abnormal facial appearance at birth or at autopsy was observed in 80%, and thymus hypoplasia, in 76%. The pregnancy was terminated in 41 of 54 cases, including an intrauterine death in one case. The 22qdel was inherited in 7.7%. CONCLUSION: Prevalence of the 22qdel is high in fetuses with CTMs. The risk of mental retardation associated with the respective risk of cardiac surgery for each type of CTM may strongly influence prenatal counseling.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 22/genética , Cardiopatías Congénitas/genética , Aborto Terapéutico , Femenino , Asesoramiento Genético , Edad Gestacional , Humanos , Hibridación Fluorescente in Situ , Discapacidad Intelectual/genética , Masculino , Embarazo , Estudios Prospectivos , Factores de RiesgoRESUMEN
Considering the high proportion of unexplained hypertrophic cardiomyopathies on the one hand and the occurrence of cardiomyopathies in several mitochondrial disorders on the other, we hypothesized that isolated hypertrophic cardiomyopathies in infancy could occasionally be the result of defects of oxidative phosphorylation. By means of a scaled-down technique, we were able to investigate oxidative phosphorylation on minute amounts of endomyocardial tissue (1 mg) in three patients with concentric hypertrophic cardiomyopathy (shortening fraction in diameter, 18% to 27%; normal mean +/- 1 SD, 33 +/- 3%) and in control subjects. Although the absolute respiratory chain enzyme activities in the endomyocardial biopsy specimens of the patients were within the low normal range, the determination of the activity ratios allowed us to ascribe hypertrophic cardiomyopathies to respiratory chain enzyme abnormalities in all three cases (complex I, two cases; multiple enzyme deficiency, one case). The respiratory chain enzyme activity ratios, which are normally constant irrespective of the tissue tested, were markedly abnormal in all three patients (cytochrome c oxidase/reduced nicotinamide-adenine dinucleotide cytochrome c reductase, 4.6 to 10.4; normal mean +/- 1 SD, 2.9 +/- 0.5). We conclude that mitochondrial disorders should be regarded as potential causes of hypertrophic cardiomyopathy in early infancy. Because cardiac catheterization is routinely performed for hemodynamic investigation of cardiomyopathies, we suggest that endomyocardial biopsies be considered as a tool for early detection of mitochondrial cardiomyopathies, especially in hypertrophic forms of the disease.