Chromosomal microarray analysis (CMA) is the first-tier test for developmental delay, autism spectrum disorders, and congenital abnormalities in postnatal diagnosis and for ultrasound abnormalities in prenatal diagnosis.
The detection of variants with clinical significance by CMA, when compared to karyotype, can increase up to 10-20% in postnatal diagnosis and up to 5-18% in prenatal diagnosis. Nevertheless CMA also detects incomplete penetrance neuro-Susceptibility Loci Copy Number Variants (SL-CNV), which although having clinical significance have an uncertain prognosis.
The aim of this study is to identify from the literature a set of SLCNV, and the corresponding penetrance for each variant, determining their occurrence in our cohort of postnatal samples ran between January 2012 and August 2018 and prenatal samples ran between January 2015 and August 2018.
We have established a 21 SL-CNV set, and from a total of 835 postnatal samples and 317 prenatal samples we have identified 36 and 11 cases, respectively, with a variant in one of the 21 established SLCNV.
The percentage of cases with a SL-CNV is relatively similar between postnatal samples (4.5%) and prenatal samples (3.5%), although the reason of referral for the two groups is not completely overlapping and also the total number of prenatal samples represents about half of the time span of the postnatal samples, which might have underestimated their occurrence. The estimated penetrance for each of the established SL-CNV present some inter-publication variability, especially concerning samples with different phenotypes. Nevertheless some variants show concordance.
Estimating the penetrance for SL-CNV, and their clinical impact for the patient or carriers in the family, is a complex task. Only time, analysis of larger cohorts, and future knowledge of genotype-environment-phenotype interactions will overcome this difficulty, decreasing uncertainty for the around 4% of patients diagnosed by CMA.info:eu-repo/semantics/publishedVersio
