Pediatria pre prax 3/2016

The utility of modern diagnostic genetic methods in clinical pediatrics

Next generation sequencing (NGS) and microarray analysis are being used with increasing frequency in pediatric genetic research. Compared with traditional „targeted“ genetic analyses that focus on a limited portion of the human genome, these methods produce significantly larger quanties of data, increasing the potential for wide-ranging and clinically meaningful applications. Chromosomal microarray analysis (CMA) has emerged as a new useful diagnostic method to identify genomic abnormalities associated with a wide range of developmental delay including mental retardation, congenital malformations, cognitive and language impairment as whole as multiple congenital abnormalities. CMA includes array comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays. Both methods are powerful for detection of genomic copy number variants (CNV) such as microdeletions or microduplications. Genomic abnormalities occur with the highest frequency (20–25 %) in children with moderate to severe mental retardation combined with congenital malformations or dysmorphic features. However, disease-causing CNVs are found in 5 –10 % children with autistic spectrum disorders and atypical phenotypes. Nowadays CMA should replace classical karyotype examination as the first-tier test for genetic evaluation of children with developmental and behavioral delay. Potent new genetic technologies may discern important diagnostic information in this group of children and their families.

Keywords: next generation sequencing (NGS), SNP and CGH microarray, pediatrics, developmental delay, intellectual disability, multiple congenital anomalies, autism