Genome sequencing reveals high diagnostic yield in children with severe sporadic developmental language disorder.

(Likely) pathogenic variants, mostly de novo, in genes or loci already implicated in neurodevelopmental disorders, plus one sex chromosome aneuploidy.

Developmental language disorder (DLD) is a neurobiological condition marked by impaired language development despite adequate linguistic input and normal intelligence; the contribution of monogenic causes is largely unknown and diagnostic genetic testing is rarely offered. This prospective cohort study performed trio-based genome sequencing in 25 individuals aged 3-25 years with severe DLD, no intellectual disability (non-verbal IQ ≥ 70), no autism spectrum disorder diagnosis and no first-degree family history of DLD or neurodevelopmental disorders. (Likely) pathogenic variants were found in nine of the 25 individuals, a molecular diagnostic yield of 36%, comprising seven autosomal dominant disorders, one autosomal recessive disorder and one sex chromosome aneuploidy; the causal variant was de novo in seven individuals. All identified variants lay in genes or loci previously implicated in neurodevelopmental disorders with variable clinical presentations, and the genetic diagnosis provided actionable information for counselling and clinical follow-up in all nine individuals. The authors support routine trio-based genetic testing in severe sporadic DLD.

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

A 36% yield in a group that is usually not tested is a strong argument for widening the indication, but it rests on 25 individuals and on tight inclusion criteria (non-verbal IQ ≥ 70, no autism, no first-degree family history), which limits how far it transfers to the patients seen in everyday language clinics. The abstract names neither the genes involved nor what genome sequencing added over a trio exome, which is the practical question for the ordering clinician. Confirming the figure would require a larger multicentre cohort with standardised language phenotyping.

Analysis by Dr Thibaut Benquey