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[Preprint]. 2024 Aug 28:rs.3.rs-4790993.
doi: 10.21203/rs.3.rs-4790993/v1.

MED13L-related disorder characterized by severe motor speech impairment

Marissa Weyer Mitchel  1 , Stefanie Turner  1 , Lauren K Walsh  1 , Rebecca I Torene  2 , Scott M Myers  1 , Cora M Taylor  1
Affiliations

MED13L-related disorder characterized by severe motor speech impairment

Marissa Weyer Mitchel et al. Res Sq. .

Abstract

Background: MED13L-related disorder is associated with intellectual disability, motor delay, and speech deficits. Previous studies have focused on broad clinical descriptions of individuals, but limited information regarding specific speech diagnoses and results of direct testing has been published to date. We conducted deep phenotyping to characterize the speech, language, motor, cognitive, and adaptive phenotypes of individuals with MED13L-related disorder.

Methods: In this cross-sectional study, we administered standardized articulation, language, motor, and cognitive testing to 17 children and adolescents (mean age 9y 9m; SD 4y 5m; range 4y 2m to 19y 7m). In-person testing was supplemented with broad developmental, medical, and behavioral information collected virtually from a cohort of 67 individuals.

Results: All individuals who completed in-person articulation testing met diagnostic criteria for speech apraxia, dysarthria, or both. Language impairment was present in all of the in-person cohort and almost all (97%) of the virtual cohort. Those who were able to complete motor testing demonstrated significant deficits in visual motor integration (mean 57.08, SD 9.26). Full scale IQs fell in the borderline to intellectual disability range, consistent with reported cognitive impairment in 97% of the virtual cohort. Notable medical features included hypotonia (83%), vision problems (72%), recurrent otitis media (58%), gastrointestinal problems (57%), and seizures (31%).

Conclusions: MED13L-related disorder is characterized by a high rate of motor speech disorders that occur in the context of globally impaired motor, language, and cognitive skills. Children would benefit from intensive, individualized speech therapy and the early adoption of augmentative communication strategies.

Keywords: Apraxia of speech; Dysarthria; MED13L; Motor impairment; Speech disorders.

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Conflict of interest statement

Declarations Competing interests The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
MED13L (NM_015335.5) exons, functional domains, and pathogenic variants of in-person cohort were plotted using the trackViewer library.(30) Note that intragenic deletions are shown relative to exons although they also span introns, thus their sizes are not to scale in this figure.
Figure 2
Figure 2
Neurodevelopmental diagnoses and adaptive skills of virtual cohort. A. Radar plot displaying the most common neurodevelopmental diagnoses reported by caregivers of children with MED13L pathogenic variants (N = 67). Developmental histories obtained by standardized telephone interview with trained genetic counselors through Simons Searchlight. B. Box and whiskers plot displaying the average standard scores of the Vineland Adaptive Behavior Scale for the four main domains (communication, daily living skills, socialization, and motor skills) and the composite score (N = 47). Mean (X), median, interquartile range, and outlier points are depicted.
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References

    1. Davis MA, Larimore EA, Fissel BM, Swanger J, Taatjes DJ, Clurman BE. The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator. Genes Dev. 2013;27(2):151–6. - PMC - PubMed
    1. Utami KH, Winata CL, Hillmer AM, Aksoy I, Long HT, Liany H, et al. Impaired development of neural-crest cell-derived organs and intellectual disability caused by MED13L haploinsufficiency. Hum Mutat. 2014;35(11):1311–20. - PubMed
    1. Muncke N, Jung C, Rüdiger H, Ulmer H, Roeth R, Hubert A, et al. Missense Mutations and Gene Interruption in PROSIT240, a Novel TRAP240-Like Gene, in Patients with Congenital Heart Defect (Transposition of the Great Arteries). Circulation. 2003;108(23):2843–50. - PubMed
    1. Asadollahi R, Oneda B, Sheth F, Azzarello-Burri S, Baldinger R, Joset P, et al. Dosage changes of MED13L further delineate its role in congenital heart defects and intellectual disability. Eur J Hum Genet. 2013;21(10):1100–4. - PMC - PubMed
    1. Asadollahi R, Zweier M, Gogoll L, Schiffmann R, Sticht H, Steindl K, et al. Genotype-phenotype evaluation of MED13L defects in the light of a novel truncating and a recurrent missense mutation. Eur J Med Genet. 2017;60(9):451–64. - PubMed

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