Clinical Characteristics and Genetic Etiology of Children With Developmental Language Disorder

Abstract

Objective: Developmental language delay (DLD) is one of the most common disabilities in childhood and can negatively affect a child's communication skills and academic and/or psychosocial development. To date, an increasing number of causative genes have been identified by diagnostic techniques like next generation sequencing. An early genetic diagnosis is important to properly prepare and counsel children and parents for possible future difficulties. Despite this, genetic assessment is usually not part of a standardized diagnostic set in children with developmental language delay. In this study, we aim to assess the diagnostic outcomes of children primarily assessed for speech and language delay who were subsequently referred for genetic etiological assessment.Methods: Medical records of children referred to the department of Otorhinolaryngology of the Wilhelmina Children's Hospital for diagnostic work-up for a suspected speech and language delay between June 2011 and December 2018 who were additionally referred to a geneticist were evaluated. Study parameters concerning medical history, behavioral problems, language development, intelligence, and hearing were recorded. Outcomes of genetic analysis were evaluated.Results: A total of 127 patients were diagnosed with a developmental language delay. Genetic analysis was conducted in 119 out of 127 patients with a language delay and eligible for this study. The median time between initial speech and language assessment and the first genetic consultation was 10 months (IQR 5.0–23.0). In 34 out of 127 patients a causative genetic diagnosis was found to explain their DLD.Conclusion: In approximately a quarter of the patients (26.8%) diagnosed with developmental language delay, a causative genetic diagnosis was confirmed. This demonstrates the opportunity to identify an underlying genetic etiology in children with developmental language delay. However, in order to optimize the diagnostic process and clinical care for these children, two important research gaps need to be addressed. First, research should focus on assessing the clinical impact and effect on treatment outcomes of a genetic diagnosis. Secondly, it is important to recognize for which children genetic testing is most beneficial.

Whole exome sequencing and polygenic assessment of a Swedish cohort with severe developmental language disorder

“…Developmental language disorder (DLD) and other neurodevelopmental disorders (NDD) share many symptoms and signs (Nitin et al 2022 ; Plug et al 2021 ). DLD is a neurodevelopmental communication disorder characterized by persistent deficits in receptive and expressive language not attributable to other biomedical conditions and results in functional, psychological, social, and/or occupational limitations (American Psychiatric Association 2022 ; Bishop et al 2016 ).…”

“…In this study, we used the term genomic DLD when referring to DLD caused by copy-number variants (CNVs). An increasing number of high-impact copy CNVs and rare variants have been identified in a proportion of DLD individuals (Chen et al 2017a , b ; Eising et al 2019 ; Kalnak et al 2018 ; Mountford et al 2022 ; Plug et al 2021 ; Villanueva et al 2015 ). The recent advances in sequencing technologies and the availability of population-level variations data have enabled genetic diagnosis in DLD and the discovery of new genes implicated in the condition (Mountford et al 2022 ).…”

Whole exome sequencing and polygenic assessment of a Swedish cohort with severe developmental language disorder

“…The boundaries between developmental language disorder (DLD) and other neurodevelopmental disorders (NDD) are not well de ned as they share many symptoms/signs (Nitin et al, 2022;Plug et al, 2021). DLD is a neurodevelopmental communication disorder characterized by persistent de cits in receptive and expressive language not attributable to other biomedical conditions and results in functional, psychological, social, and/or occupational limitations (American Psychiatric Association, 2022; Bishop et al, 2016).…”

“…The recent advances in sequencing technologies and the availability of population-level variations data have enabled genetic diagnosis in DLD and the discovery of new genes implicated in the condition (Mountford et al, 2022). Yet, some challenges exist, including the considerable phenotypic and genetic overlap between DLD and other NDD, as multiple genes implicated in the pathogenesis of DLD have also been implicated in other NDD (Mountford et al, 2022;Plug et al, 2021). Furthermore, disentangling the polygenic contribution in DLD is lagging compared to the monogenic forms.…”

What happens in the brain?

“…Further work is needed to see whether the anatomical differences discovered by Krishnan et al and others cause DLD: in an association study like this, it is equally possible that DLD is responsible for the observed brain changes. In addition, it remains to be seen whether the molecules responsible for the reduced levels of myelin found in the basal ganglia and Broca’s area are coded by genes that have already been implicated in DLD ( Plug et al, 2021 ).…”