Molecular bases of hearing loss in multi-systemic mitochondrial cytopathy

Abstract

Purpose: Hearing loss is a common clinical feature in classic mitochondrial syndromes. The purpose of this study was to evaluate the diverse molecular etiologies and natural history of hearing loss in multi-systemic mitochondrial cytopathies and the possible correlation between degree of hearing loss and neurological phenotype. Methods: In this retrospective study we evaluated the clinical features and molecular bases of hearing loss associated with multi-systemic mitochondrial cytopathy. Forty-five patients with sensorineural hearing loss and definite diagnosis of mitochondrial cytopathy according to the published diagnostic criteria were studied. Results: The sensorineural hearing loss was progressive and for the most part symmetrical with involvement of the higher frequencies. Both cochlear and retrocochlear involvement were found in this cohort. No correlation was found between the degree of hearing loss and the number and severity of neurological manifestations. Deleterious mtDNA point mutations of undisputed pathogenicity were identified in 18 patients. The A3243G mutation was the most frequently encountered among this group. MtDNA depletion, over-replication, and multiple deletions were found in further 11 cases.

Association between idiopathic hearing loss and mitochondrial DNA mutations: A study on 169 hearing-impaired subjects

“…Non-syndromic SNHL associated with mtDNA mutations is generally progressive (4,5), involving mainly higher frequencies (6–8) and is generally symmetric HL. The onset of HL usually occurs in childhood, is predominantly post-lingual and may be accompanied with vertigo (9) and tinnitus (10,11).…”

Hearing loss in children with mitochondrial disorders

“…Previously, the hearing loss associated with mitochondrial disorders has been characterized as a high-frequency, progressive, sensorineural loss [11][12][13]. There have also been some reports of sensorineural loss affecting all frequencies equally.…”

“…Therefore, mitochondrial abnormalities can lead to multisystem disorders such as the mitochondrial encephalomyopathies: Kearns-Sayre syndrome (KSS) [5]; mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS) [6]; and myoclonic epilepsy associated with ragged-red fibers (MERRF) [7], all of which may include sensorineural hearing loss (often progressive) as a symptom [8][9][10]. Hearing loss associated with mtDNA mutations has been characterized as a progressive, sensorineural hearing loss across higher frequencies or across all frequencies [11][12][13].…”

Mitochondrial disease in children

“…It may be of cochlear origin or be caused by an auditory neuropathy. One study suggested that 40% of individuals with mitochondrial disease have hearing loss [72]. The most frequent genetic variant predisposing to mitochondrial nonsyndromic SNHL is m.1555A>G in the MT‐RNR gene encoding a mitochondrial rRNA.…”