The Role of Genetic Testing in Pediatric Expressive Language Delay: Evidence from the National Brain Gene Registry

Abstract

Background/Objectives: Speech and language delay (SLD) is one of the most prevalent developmental conditions in childhood, with post-pandemic data indicating a notable increase in identified cases. Within this group, expressive language disorder (ELD) frequently appears alongside neurodevelopmental disorders such as autism spectrum disorder (ASD), epilepsy, and intellectual disability. Although awareness of ELD has grown, the role of genetic testing in its evaluation remains unclear, as such testing is not routinely pursued for isolated expressive language concerns. This gap highlights the need to better define the diagnostic value of genetic analysis and to examine the interval between an ELD diagnosis and the return of genetic testing results. Methods: This study investigated genetic contributions to ELD using the National Brain Gene Registry (BGR), a multisite database of rare neurodevelopmental disorders. Participants with ICD-10 code F80.1 were identified through electronic health records; demographic data, comorbidities, genetic variants, inheritance patterns, age at diagnosis, and timing of interventions were analyzed. Results: Of 687 BGR participants, 32 (4.7%) had documented ELD. The cohort, aged 3–19 years, presented with common comorbidities like developmental delays, ASD, epilepsy, and hypotonia. Across 42 genes, 49 unique variants were identified: 26 pathogenic or likely pathogenic, 22 variants of uncertain significance, and one benign variant. Seventeen variants were de novo, and 10 participants carried multiple variants. Most children (80%) received an expressive language diagnosis prior to genetic testing, with reports returned an average of 1.5 years following the diagnosis. Conclusions: Overall, children with ELD commonly carry genetic variants and neurodevelopmental comorbidities, yet genetic testing is typically pursued well after diagnosis and does not currently alter early management. These findings underscore the need for clearer, evidence-based guidelines to define when genetic testing adds diagnostic or prognostic value in the evaluation of ELD.