RESUMEN
PURPOSE: To evaluate the performance of chromosomal microarray analysis (CMA) in fetuses with nuchal translucency (NT) > 95th percentile. Secondary objectives were to analyze these results according to NT thickness, below or above 3.5 mm, and those without associated anomalies. METHODS: This observational single-cohort study was conducted between 2015 and 2018 in fetuses with NT > 95th percentile. Following an invasive test, quantitative fluorescence-polymerase chain reaction (QF-PCR) was performed, and if normal, CMA was performed. Pathogenic copy number variants (CNVs), non-reported pathogenic CNV, pathogenic autosomal recessive variants and variants of unknown significance (VUS) were analysed. RESULTS: One-hundred and sixty-two fetuses with NT > 95th percentile, normal QF-PCR and CMA were included. Amongst 128 fetuses with NT between the 95th percentile and 3.5 mm, one (0.8%) had a pathogenic CNV, four (3.1%) had non-reported pathogenic CNV, one (0.8%) had pathogenic autosomal recessive variant and 13 (10.2%) had VUS. Amongst 34 fetuses with NT ≥ 3.5 mm, four (11.8%) had pathogenic CNV, one (2.9%) had non-reported pathogenic CNV, one (2.9%) had pathogenic autosomal recessive variant and four (11.8%) had VUS. Four in 162 (2.5%) fetuses had CNVs at the chromosome 16p13.11 region. Amongst 154 fetuses without structural abnormalities and normal QF-PCR, three (1.9%) had a pathogenic CNV, 5 (3.2%) had non-reported pathogenic CNV, one (0.6%) autosomal recessive pathogenic CNV and 16 (10.4%) had VUS. CONCLUSION: Pathogenic CNVs were found in 1% of fetuses with an NT thickness between the 95th percentile and 3.5 mm and in 12% of fetuses with NT ≥ 3.5 mm. CNVs were found at the 16p13.11 region in 2.5% of cases.
Asunto(s)
Aberraciones Cromosómicas , Medida de Translucencia Nucal , Embarazo , Femenino , Humanos , Medida de Translucencia Nucal/métodos , Diagnóstico Prenatal/métodos , Estudios de Cohortes , Feto/diagnóstico por imagenRESUMEN
BACKGROUND AND OBJECTIVE: Conventional cytogenetics diagnoses 3-5% of patients with unexplained developmental delay/intellectual disability and/or multiple congenital anomalies. The Multiplex Ligation-dependent Probe Amplification increases diagnostic rates from between 2.4 to 5.8%. Currently the comparative genomic hybridisation array or aCGH is the highest performing diagnostic tool in patients with developmental delay/intellectual disability, congenital anomalies and autism spectrum disorders. Our aim is to evaluate the efficiency of the use of aCGH as first-line test in these and other indications (epilepsy, short stature). PATIENTS AND METHOD: A total of 1000 patients referred due to one or more of the abovementioned disorders were analysed by aCGH. RESULTS: Pathogenic genomic imbalances were detected in 14% of the cases, with a variable distribution of diagnosis according to the phenotypes: 18.9% of patients with developmental delay/intellectual disability; 13.7% of multiple congenital anomalies, 9.76% of psychiatric pathologies, 7.02% of patients with epilepsy, and 13.3% of patients with short stature. Within the multiple congenital anomalies, central nervous system abnormalities and congenital heart diseases accounted for 14.9% and 10.6% of diagnoses, respectively. Among the psychiatric disorders, patients with autism spectrum disorders accounted for 8.9% of the diagnoses. CONCLUSIONS: Our results demonstrate the effectiveness and efficiency of the use of aCGH as the first line test in genetic diagnosis of patients suspected of genomic imbalances, supporting its inclusion within the National Health System.