Microarray application in prenatal diagnosis: a position statement from the cytogenetics working group of the Italian Society of Human Genetics (SIGU), November 2011.

Objectives: At present, a precise guideline establishing chromosome microarray analysis (CMA) applications and platforms in the prenatal setting does not exist. The actual controversial question is whether CMA technologies can or should shortly replace the standard karyotype in prenatal diagnosis practice. Methods: Based on review of the recent literature and actual knowledge and experiences of all participants, the SIGU Committee proposes recommendations for the use of CMA in prenatal testing. Results: Dataset collections reported in the medical literature clearly show a significant incidence of pathogenic CNVs at 6.4% in the group of pregnancies with ultrasound fetal abnormalities and normal karyotype and the detected CNVs are more likely to have a relevant role in terms of nosology for the fetus and for the assessment of reproductive risks for the couples. The estimation of the frequencies of variations of unclear significance (VOUS) varies depending on the different CMA platforms used spanning from targeted arrays, for which a 0-4% frequency of VOUS has been reported, to high resolution whole genome SNP arrays for which the estimated incidence of VOUS was of 9-12%. Conclusions: Presently CMA analysis can be considered a second-tier diagnostic test to be used after a standard karyotype in selected group of pregnancies, such as those with single (apparently isolated) or multiple US fetal abnormalities, with de novo chromosomal rearrangements, even if apparently balanced, and those with supernumerary marker chromosomes.