Diagnostic Yield and Clinical Actionability of Genetic Testing in Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis

This systematic review and meta-analysis (PRISMA 2020) assesses the diagnostic yield and clinical actionability of genetic testing in neurodevelopmental disorders: autism spectrum disorder, intellectual disability and global developmental delay. A search of PubMed and Web of Science, supplemented by an AI-assisted search (Undermind) and reference screening, included 23 studies, 22 of them in the diagnostic yield meta-analysis (7641 patients tested). Pooled diagnostic yield was 28% (95% CI 21-35%) and pooled clinical actionability 58% (95% CI 44-72%) across 16 studies (1538 diagnosed patients), robust at 54-64% in sensitivity analyses. Yield followed a gradient by modality: 16% for chromosomal microarray, 36% for exome and 43% for genome sequencing (p < 0.0001). Certainty of evidence was very low by GRADE, reflecting substantial heterogeneity (I² above 95%) and observational designs.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Useful figures to position exome and genome sequencing against chromosomal microarray in neurodevelopmental disorders: beyond yield, more than one diagnosis in two changes management (pharmacological optimisation, comorbidity surveillance, end of the diagnostic odyssey). The estimates must be handled with caution: extreme heterogeneity and very low GRADE certainty, acknowledged by the authors themselves.

Analysis by Dr Thibaut Benquey