Chromosomal microarray in postnatal diagnosis of congenital anomalies and neurodevelopmental disorders in Serbian patients

Abstract

Background Array‐based genomic analysis is a gold standard for the detection of copy number variations (CNVs) as an important source of benign as well as pathogenic variations in humans. The introduction of chromosomal microarray (CMA) has led to a significant leap in diagnostics of genetically caused congenital malformations and neurodevelopmental disorders, with an average diagnostic yield of 15%. Here, we present our experience from a single laboratory perspective in four years’ postnatal clinical CMA application. Methods DNA samples of 430 patients with congenital anomalies and/or neurodevelopmental disorders were analyzed by comparative genome hybridization using oligonucleotide‐based microarray platforms. Interpretation of detected CNVs was performed according to current guidelines. The detection rate (DR) of clinically significant findings (pathogenic/likely pathogenic CNVs) was calculated for the whole cohort and isolated or combined phenotypic categories. Results A total of 140 non‐benign CNVs were detected in 113/430 patients (26.5%). In 70 patients at least one CNV was considered clinically significant thus reaching a diagnostic yield of 16.3%. The more complex the phenotype, including developmental delay/intellectual disability (DD/ID) as a prevailing feature, the higher the DR of clinically significant CNVs is obtained. Isolated congenital anomalies had the lowest, while the “dysmorphism plus” category had the highest diagnostic yield. Conclusion In our study, CMA proved to be a very useful method in the diagnosis of genetically caused congenital anomalies and neurodevelopmental disorders. DD/ID and dysmorphism stand out as important phenotypic features that significantly increase the diagnostic yield of the analysis.

Clinical evaluation of rare copy number variations identified by chromosomal microarray in a Hungarian neurodevelopmental disorder patient cohort

“…Our diagnostic yield (37.18%) is quite high compared to the estimated 15-20% yield of CMA methods, albeit these estimates are often based on studies where selection criteria were rather broad and CMA resolution was relatively low [2]. Our diagnostic yield is comparable to several studies with smaller patient groups and/or similarly strict selection criteria [5][6][7][8][9][10][11][12][13][14][15].…”

Clinical validation of the nursing diagnosis “Risk for delayed child development”

“…There were three significant statistical associations of risk factors with the absence of CD milestones: "Genetic disorders", "Congenital disorders", and "Impaired cognitive development of parents", similar to research results that emphasize these factors as associated with delayed CD (19,(24)(25)(26) . Similarly, genetic and congenital disorders are pointed out as factors that have important neurological consequences for children (26,27) .…”

Validação clínica do diagnóstico de enfermagem “Risco de atraso no desenvolvimento infantil”

“…Verificaram-se três associações estatísticas significativas dos fatores de risco com a ausência de marcos do DI: "Distúrbios genéticos", "Distúrbios congênitos" e "Desenvolvimento cognitivo dos pais prejudicado", assemelhando-se a resultados de pesquisas que destacam esses fatores como associados ao atraso no DI (19,(24)(25)(26) . Igualmente, os distúrbios genéticos e congênitos são apontados como fatores que acarretam consequências neurológicas importantes para a criança (26,27) .…”