Cochleovestibular Phenotype in a Rare Genetic MED13L Mutation

Overview

Journal J Int Adv Otol

Publisher Aves

Specialty Otorhinolaryngology

Date 2024 Mar 7

PMID 38454295

Authors

Mariam Shahid

Mohamed Ahmed

Shivaram Avula

Soumit Dasgupta

Affiliations

Soon will be listed here.

Abstract

The gene MED13 participates in transcription. The MED13L gene is a paralog of MED13 that is involved in developmental gene expression. Mutations in the gene have been shown to result in a heterogenous phenotype affecting several physiological systems. Hearing loss has been reported very rarely, and vestibular weakness has never been reported in the condition. In this report, we present a mutation of MED13L in c.1162A > T (p.Arg388Ter), where we detail and describe a cochleovestibular phenotype with objective vestibulometry for the first time. The child showed bilateral sloping sensorineural hearing loss, a bilateral vestibular weakness, and an inner ear vestibular structural abnormality on imaging. Early intervention with hearing aids and vestibular rehabilitation led to a favorable outcome in terms of speech, communication, and balance. We emphasize the importance of comprehensive audiovestibular assessment in children diagnosed with MED13L mutations for effective management of these children.

References

Lal D, Neubauer B, Toliat M, Altmuller J, Thiele H, Nurnberg P . Increased Probability of Co-Occurrence of Two Rare Diseases in Consanguineous Families and Resolution of a Complex Phenotype by Next Generation Sequencing. PLoS One. 2016; 11(1):e0146040. PMC: 4720433. DOI: 10.1371/journal.pone.0146040. View

Ansari S, Morse R . Mechanisms of Mediator complex action in transcriptional activation. Cell Mol Life Sci. 2013; 70(15):2743-56. PMC: 11113466. DOI: 10.1007/s00018-013-1265-9. View

Adegbola A, Musante L, Callewaert B, Maciel P, Hu H, Isidor B . Redefining the MED13L syndrome. Eur J Hum Genet. 2015; 23(10):1308-17. PMC: 4592099. DOI: 10.1038/ejhg.2015.26. View

Utami K, Winata C, Hillmer A, Aksoy I, Long H, Liany H . Impaired development of neural-crest cell-derived organs and intellectual disability caused by MED13L haploinsufficiency. Hum Mutat. 2014; 35(11):1311-20. DOI: 10.1002/humu.22636. View

Ritter K, Martin D . Neural crest contributions to the ear: Implications for congenital hearing disorders. Hear Res. 2018; 376:22-32. PMC: 6456423. DOI: 10.1016/j.heares.2018.11.005. View

Poot M . Mutations in Mediator Complex Genes , and Mediate Overlapping Developmental Syndromes. Mol Syndromol. 2020; 10(5):239-242. PMC: 6997798. DOI: 10.1159/000502346. View

Calpena E, Hervieu A, Kaserer T, Swagemakers S, Goos J, Popoola O . De Novo Missense Substitutions in the Gene Encoding CDK8, a Regulator of the Mediator Complex, Cause a Syndromic Developmental Disorder. Am J Hum Genet. 2019; 104(4):709-720. PMC: 6451695. DOI: 10.1016/j.ajhg.2019.02.006. View

Boutry-Kryza N, Labalme A, Till M, Schluth-Bolard C, Langue J, Turleau C . An 800 kb deletion at 17q23.2 including the MED13 (THRAP1) gene, revealed by aCGH in a patient with a SMC 17p. Am J Med Genet A. 2011; 158A(2):400-5. DOI: 10.1002/ajmg.a.34222. View

Asadollahi R, Zweier M, Gogoll L, Schiffmann R, Sticht H, Steindl K . 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):451-464. DOI: 10.1016/j.ejmg.2017.06.004. View

10.

Poss Z, Ebmeier C, Taatjes D . The Mediator complex and transcription regulation. Crit Rev Biochem Mol Biol. 2013; 48(6):575-608. PMC: 3852498. DOI: 10.3109/10409238.2013.840259. View

11.

Manzari L, Tramontano M . Suppression Head Impulse Paradigm (SHIMP) in evaluating the vestibulo-saccadic interaction in patients with vestibular neuritis. Eur Arch Otorhinolaryngol. 2020; 277(11):3205-3212. DOI: 10.1007/s00405-020-06085-6. View

12.

Blok L, Hiatt S, Bowling K, Prokop J, Engel K, Cochran J . De novo mutations in MED13, a component of the Mediator complex, are associated with a novel neurodevelopmental disorder. Hum Genet. 2018; 137(5):375-388. PMC: 5973976. DOI: 10.1007/s00439-018-1887-y. View

13.

Trivisano M, De Dominicis A, Micalizzi A, Ferretti A, Dentici M, Terracciano A . MED13 mutation: A novel cause of developmental and epileptic encephalopathy with infantile spasms. Seizure. 2022; 101:211-217. DOI: 10.1016/j.seizure.2022.09.002. View