Evaluation of: Wapner RJ, Martin CL, Levy B et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N. Engl. J. Med. 367(23), 2175–2184 (2012).
Prenatal diagnosis is now offered to high-risk pregnancies, including advanced maternal age, ultrasound anomalies and positive Down’s syndrome screening, and karyotype on cultured fetal material is the test of choice to screen these pregnancies. However, microscope analysis can only detect gross chromosome abnormalities, highlighting the need for more sensitive techniques. It has recently been established that the higher resolution of microarray-based platforms can increase the diagnostic yield, offering more information to couples, and it is being discussed as a replacement to the standard karyotype. Conversely, the very high sensitivity of microarray-based analysis allows us to detect small microdeletions/microduplications (copy number variations) with unknown functional role and difficult genotype/phenotype correlation. In addition, the new copy number variation syndromes are often associated with variable outcomes, ranging from normal to severely affected individuals. This means that the microarray-based analysis introduced routinely in prenatal diagnosis needs to answer the question: are laboratory staff, clinical geneticists and counselors really experienced enough to manage these new scenarios?