Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development

Kaspi, Antony; Hildebrand, Michael S.; Jackson, Victoria E.; Braden, Ruth; Reyk, Olivia van; Howell, Tegan; Debono, Simone; Lauretta, Mariana; Morison, Lottie; Coleman, Matthew; Webster, Richard; Coman, David; Goel, Himanshu; Wallis, Mathew; Dabscheck, Gabriel; Downie, Lilian; Baker, Emma K.; Parry-Fielder, Bronwyn; Ballard, Kirrie J.; Harrold, Eva; Ziegenfusz, Shaun; Bennett, Mark F; Robertson, Erandee; Wang, Long; Boys, Amber; Fisher, Simon E.; Amor, David J.; Scheffer, Ingrid E.; Bahlo, Melanie; Morgan, Angela

doi:10.1101/2022.05.15.22274630

Cited by 2 publications

(1 citation statement)

References 63 publications

(76 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, impaired social behaviour was associated with impaired language skills, but not vice versa. Further, it is important to recognise that speech and language impairment can be present in the absence of ID, with linguistic behaviours having their own biologically driven neurological pathways, (44).…”

Section: Discussionmentioning

confidence: 99%

CDK13-related disorder: a deep characterization of speech and language abilities and addition of 33 novel cases

et al. 2023

View full text Add to dashboard Cite

Speech and language impairments are central features of CDK13-related disorder. While pathogenic CDK13 variants have been associated with childhood apraxia of speech (CAS), a systematic characterisation of communication has not been conducted. Here we examined speech, language, non-verbal communication skills, social behaviour and health and development in 41 individuals with CDK-13 related disorder (male = 22, median-age 7 years 1 month, range 1-25 years; 33 novel). Most participants used augmentative and alternative communication (AAC) in early childhood (24/41). CAS was common (14/22). Performance varied widely across intellectual ability, social behaviour and expressive language skills, with participants ranging from within average through to the severely impaired range. Receptive language was signi cantly stronger than expressive language ability. Social motivation was a relative strength. In terms of broader phenotype, a quarter had one or more of: renal, urogenital, musculoskeletal and cardiac malformations, vision impairment, ear infections and/or sleep disturbance. All had gross and ne motor impairments (41/41). Other conditions included mild-moderate intellectual disability (16/22) and autism (7/41). No genotype-phenotype correlations were found. Recognition of CAS, a rare speech disorder, is required to ensure appropriately targeted therapy. The high prevalence of speech and language impairment underscores the importance of tailored speech therapy, particularly early access to AAC supports.commonly impacted areas of neurodevelopment in CDK13-related disorder (5, 6, 8,10,13,14). Yet whilst communication di culties are ubiquitously reported, there has been no speci city to the clinical diagnoses, with very general terms such as 'speech and language delay' being used. Nor have studies used standardised measures/assessment protocols. A variant in CDK13 was recently associated with a rare and severe speech disorder, childhood apraxia of speech (CAS), in a gene discovery cohort of children ascertained for CAS (13). However, there has been no systematic reverse phenotyping evaluation of speech or language de cits in a cohort of individuals with pathogenic CDK13 variants to date to con rm this association with CAS. Further, the absence of a comprehensive speech and language evaluation in this population limits prognostic counselling and the provision of targeted intervention. Here, we systematically characterise speech and language abilities in children with CDK13-related disorder using standardised outcome measures. Methods ParticipantsInclusion criteria were a molecularly con rmed pathogenic diagnosis of CDK13-related disorder. Exclusion criteria were the existence of other pathogenic variants in other neurodevelopmental genes. Participants were recruited via an online CDK13 support group or via their treating clinical geneticist. The Royal Children's Hospital Human Research Ethics Committee provided ethical approval (HREC 37353A). Caregivers provided written and informed consent for their children to partic...

show abstract

Section: Discussionmentioning

confidence: 99%