Non-syndromic mitochondrial hearing loss refers to a specific type of hearing impairment caused by mitochondrial dysfunction but is not associated with other syndromic features. Mitochondria are cellular structures responsible for producing energy, and when mitochondrial DNA (mtDNA) is dysfunctional, it can lead to various disorders, including hearing loss.
Non-syndromic mitochondrial hearing loss genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Critical features of non-syndromic mitochondrial hearing loss include:
- Isolated Hearing Loss: The primary manifestation is bilateral sensorineural hearing loss, which affects both ears and involves damage to the inner ear (cochlea) or the auditory nerve.
- Maternal Inheritance: Mitochondrial DNA is inherited maternally, meaning that individuals with non-syndromic mitochondrial hearing loss often have a family history on the maternal side.
- Variable Severity: Hearing loss can vary among affected individuals, ranging from mild to profound.
- Progressive Nature: In some cases, the hearing loss may be progressive, worsening over time.
- Preservation of Other Organs: Unlike syndromic mitochondrial disorders, non-syndromic mitochondrial hearing loss typically does not involve other organs or systems.
- Onset: Hearing loss may occur from birth or later in childhood or adulthood.
- Mitochondrial DNA Mutations: Non-syndromic mitochondrial hearing loss is associated with specific mutations in the mitochondrial DNA.
- Lack of Other Syndromic Features: Unlike some mitochondrial disorders that affect multiple systems (syndromic mitochondrial disorders), non-syndromic mitochondrial hearing loss does not present with additional clinical features.
Diagnosis of non-syndromic mitochondrial hearing loss involves genetic testing to identify mutations in the mitochondrial DNA associated with hearing loss. Audiological assessments, such as pure-tone audiometry and auditory brainstem response (ABR) testing, are used to characterize the extent and nature of the hearing loss.
Management of non-syndromic mitochondrial hearing loss primarily involves supportive measures, including hearing aids or cochlear implants, to improve communication and quality of life. There is currently no cure for mitochondrial disorders, but ongoing research aims to explore potential therapeutic interventions.
Genetic counseling is essential for families affected by non-syndromic mitochondrial hearing loss to understand the inheritance pattern, assess the risk of having affected children, and discuss available reproductive options. Early diagnosis and intervention are crucial for managing the condition and providing appropriate support for affected individuals.
More Information
The m.1555A>G mutation in the 12S rRNA gene of mitochondrial DNA is associated with non-syndromic deafness and deafness induced by aminoglycosides (bactericidal antibiotics). This variant has been identified in 0.6-12% of people with hearing impairment, in contrast to 0.1-0.3% of the general population. Those individuals with this mutation usually pass the newborn hearing test but develop permanent and profound hearing loss after treatment with aminoglycans, even when drug levels are within the therapeutic range. Penetrance is incomplete, i.e., it does not affect all individuals with the variant equally, but the risk of hearing loss is markedly increased with exposure to aminoglycans than without exposure.
Studies indicate that after exposure to aminoglycans, most people carrying the variant, almost 100%, develop deafness. The clinical manifestation is influenced by the degree of heteroplasmy (different proportions of mutated mitochondrial genomes present in each cell, tissue, or patient), environmental factors, and other genetic modifiers (e.g., the presence of mutations in other genes that may increase the risk of hearing loss such as the GJB2 gene).
Non-syndromic mitochondrial hearing loss genetic testing analyzes the m.1555A>G mutation in the 12S rRNA gene of mitochondrial DNA.
The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).
