Otological Features of Patients with Musculocontractural Ehlers-Danlos Syndrome Caused by Pathogenic Variants in CHST14 (mcEDS- CHST14)

Masayuki Kawakita; Satoshi Iwasaki; Hideaki Moteki; Shin-Ya Nishio; Tomoki Kosho; Shin-Ichi Usami

doi:10.3390/genes14071350

Otological Features of Patients with Musculocontractural Ehlers-Danlos Syndrome Caused by Pathogenic Variants in CHST14 (mcEDS- CHST14)

Genes (Basel). 2023 Jun 27;14(7):1350. doi: 10.3390/genes14071350.

Authors

Masayuki Kawakita¹, Satoshi Iwasaki^{2

3}, Hideaki Moteki^{2

4}, Shin-Ya Nishio², Tomoki Kosho^{5

6

7

8}, Shin-Ichi Usami²

Affiliations

¹ Asama General Hospital, Saku 385-8558, Japan.
² Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
³ Department of Otolaryngology, International University of Health and Welfare, Mita Hospital, Tokyo 108-8329, Japan.
⁴ Department of Otolaryngology, Aizawa Hospital, Matsumoto 390-8621, Japan.
⁵ Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
⁶ Center for Medical Genetics, Shinshu University Hospital, Matsumoto 390-8621, Japan.
⁷ Division of Clinical Sequencing, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
⁸ Research Center for Supports to Advanced Science, Shinshu University, Matsumoto 390-8621, Japan.

Abstract

Musculocontractural Ehlers-Danlos syndrome (EDS) caused by pathogenic variants in CHST14 (mcEDS-CHST14) is a subtype of EDS characterized by multisystem malformations and progressive fragility-related manifestations. A recent international collaborative study showed that 55% of mcEDS-CHST14 patients had hearing loss (HL), more commonly of the high-frequency type. Here, we report the first systemic investigation of the otological features of patients with this disorder based on the world's largest cohort at Shinshu University Hospital. Nine patients [18 ears; four male and five female patients; mean age, 18 years old (range, 10-28)] underwent comprehensive otological evaluation: audiogram, distortion product otoacoustic emission (DPOAE) test, and tympanometry. The audiogram, available in all 18 ears, showed HL in eight patients (8/9, 89%) and in 14 ears (14/18, 78%): bilateral in six patients (6/9, 67%) and unilateral in two (2/9, 22%); mild in eight ears (8/18, 44%) and moderate in six (6/18, 33%); and high-frequency HL in five (5/18, 28%) and low-frequency HL in five (5/18, 28%). An air-bone gap was detected in one ear (1/18, 6%). DPOAE was available in 13 ears, with the presence of a response in five (5/13, 38%) and the absence in eight (8/13, 62%), including in three ears of normal hearing. Tympanometry results were available in 12 ears: Ad type in nine (9/12, 75%) and As type in one (1/12, 8.3%). Patients with mcEDS-CHST14 had a high prevalence of HL, typically sensorineural and bilateral, with mild to moderate severity, of high-frequency or low-frequency type, and sometimes with no DPOAE response. The pathophysiology underlying HL might be complex, presumably related to alterations of the tectorial membrane and/or the basilar membrane of Corti associated with disorganized collagen fibril networks. Regular and careful check-ups of hearing using multiple modalities are recommended for mcEDS-CHST14 patients.

Keywords: hearing loss; mcEDS-CHST14; musculocontractural Ehlers–Danlos syndrome; no DPOAE response; sensorineural.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Deafness*
Ehlers-Danlos Syndrome* / genetics
Ehlers-Danlos Syndrome* / pathology
Extracellular Matrix / pathology
Female
Humans
Male
Skin / pathology
Sulfotransferases / genetics

Substances

Sulfotransferases
dermatan-4-sulfotransferase-1

Grants and funding

This research was funded by Grants-in-Aid for Scientific Research (B) (T.K.) (#19H03616) from the Ministry of Education, Culture, Sports, Science and Technology; the Initiative on Rare and Undiagnosed Diseases (IRUD) (21445007) (2023-5) (T.K.), Japan Agency for Medical Research and Development (AMED); and Research Programme on Policy of Measures for Intractable/Rare Diseases (23810379) (2023-5) (T.K.), Ministry of Health, Labour and Welfare, Japan.