Diagnostic yield of array-CGH in children with suspected rare disease

TL;DR

This study shows that aCGH has a 12.2% diagnostic yield in children with suspected rare diseases, especially those with multiple symptoms.

Contribution

The study provides empirical evidence on aCGH's diagnostic effectiveness in pediatric rare disease cases with varied clinical features.

Findings

aCGH had a 12.2% diagnostic yield, with 90.9% of conclusive results being pathogenic.

Higher diagnostic yield was observed in patients with coordination problems, learning disorders, and microcephaly.

Chromosomes 15 and 16 were most frequently affected by copy number variations (CNVs).

Abstract

This study aims to analyze the diagnostic yield of aCGH in pediatric patients with suspected rare diseases, focusing on its diagnostic value and effectiveness depending on different clinical symptoms.

This observational study analyzed 600 aCGH tests performed in a pediatric unit (2018–2022) for patients with suspected rare diseases. DNA was extracted from peripheral blood; aCGH resolution was adjusted to clinical features. CNVs were classified per international guidelines. Forty sociodemographic, clinical, and genetic variables were analyzed using IBM SPSS v.26.

Of the 600 patients analyzed, 543 were included in the final study. The median age was 4.7 years (IQR: 6.36 years), and 66.3% were male. Most referrals came from pediatric neurology (84.3%), and the most common clinical manifestations were altered phenotype (38.6%), autism spectrum disorder (ASD) (38.6%), dysmorphia (28.2%), global developmental delay (GDD) (27.1%), and intellectual disability (21.0%). Among 543 patients, 30.4% presented CNVs, with 12.4% identified as pathogenic and 18.1% as variants of uncertain significance. Diagnostic yield was 12.2%, with 66 conclusive results — 90.9% of which were pathogenic. CNVs were most frequently detected on chromosomes 15 and 16. The highest yield was observed in clinical features such as coordination problems (35.7%), learning disorders (28.6%), and microcephaly (22.6%).

The diagnostic yield of aCGH in this study was 12.2%. The test demonstrated higher diagnostic value in patients with multiple clinical manifestations, highlighting the importance of aCGH as a first-line diagnostic tool for rare diseases. This technique enables earlier diagnosis, improves clinical management, and provides better counseling for affected families.