mitochondrial nonsyndromic sensorineural deafness

Mitochondrial nonsyndromic sensorineural deafness refers to a type of hearing loss that is caused by mutations in the mitochondrial DNA (mtDNA) and is not associated with any other signs or symptoms. This condition is characterized by sensorineural hearing loss, which affects the inner ear's ability to convert sound vibrations into electrical signals that are transmitted to the brain.

Causes and Transmission

Mitochondrial nonsyndromic sensorineural deafness is caused by mutations in the mtDNA, which are inherited from one's mother. This means that the condition is passed down from mother to child, as only egg cells contribute mitochondria to the fertilized egg. The mutations can be matrilineal, meaning they are inherited through the maternal line.

Characteristics

The hearing loss associated with mitochondrial nonsyndromic sensorineural deafness can vary in severity and onset. Some individuals may experience mild hearing loss, while others may have more severe or profound hearing impairment. The condition is often bilateral, affecting both ears.

Genes Associated with Mitochondrial Nonsyndromic Hearing Loss

Several genes have been associated with mitochondrial nonsyndromic hearing loss, including:

• MT-RNR1: mutations in this gene can be associated with predisposition to aminoglycoside ototoxicity and/or late-onset sensorineural hearing loss.
• MTTS1: mutations in this gene have also been linked to mitochondrial nonsyndromic hearing loss.

Diagnosis

The diagnosis of mitochondrial nonsyndromic sensorineural deafness is established through molecular genetic testing, which identifies pathogenic variants in the mtDNA. A proband with suggestive findings and a pathogenic variant in one of the genes associated with mitochondrial nonsyndromic hearing loss and deafness can confirm the diagnosis.

References

• [1] Mutations in mitochondrial DNA (mtDNA) have been found to be associated with nonsyndromic sensorineural hearing loss. Matrilineal relatives within and among families carrying certain pathogenic mitochondrial mutations exhibit a wide range of penetrance, severity, and age of onset of hearing loss, indicating that the mitochondrial mutations by themselves are not sufficient to cause the condition.
• [10] Mitochondrial nonsyndromic hearing loss and deafness is characterized by sensorineural hearing loss (SNHL) of variable onset and severity. Pathogenic variants in MT-RNR1 can be associated with predisposition to aminoglycoside ototoxicity and/or late-onset SNHL.
• [12] Clinical characteristics: Mitochondrial nonsyndromic hearing loss and deafness is characterized by sensorineural hearing loss (SNHL) of variable onset and severity. Pathogenic variants in MT-RNR1 can be associated with predisposition to aminoglycoside ototoxicity and/or late-onset SNHL. *

Mitochondrial nonsyndromic sensorineural deafness is a type of hearing loss that occurs due to changes in the DNA in mitochondria, which are the energy-producing structures within cells. This condition results in sensorineural hearing loss (SNHL), which can vary in onset and severity.

According to various sources [6][7], mitochondrial nonsyndromic sensorineural deafness is characterized by:

• Sensorineural hearing loss of variable onset and severity
• Hearing loss that is not associated with other signs or symptoms

It's worth noting that this condition accounts for fewer than 1% of cases in the United States [4]. The remaining cases of genetic hearing loss are often associated with syndromic conditions, which present with additional clinical features.

In terms of specific symptoms, mitochondrial nonsyndromic sensorineural deafness is primarily characterized by hearing loss. However, it's essential to consult a medical professional for an accurate diagnosis and to rule out other potential causes of hearing loss.

References: [4] Mitochondrial nonsyndromic deafness, which results from changes to the DNA in mitochondria, occurs in fewer than 1% of cases in the United States. [6] Jun 14, 2018 — Mitochondrial nonsyndromic hearing loss and deafness is characterized by sensorineural hearing loss (SNHL) of variable onset and severity. [7] Feb 1, 2016 — Nonsyndromic hearing loss is a partial or total loss of hearing that is not associated with other signs and symptoms.

Diagnostic Tests for Mitochondrial Nonsyndromic Sensorineural Deafness

Mitochondrial nonsyndromic sensorineural deafness is a type of hearing loss caused by mutations in the mitochondrial DNA. The diagnosis of this condition involves genetic testing to identify these mutations.

• Genetic Testing: Genetic testing is the primary diagnostic tool for mitochondrial nonsyndromic sensorineural deafness. This test can be performed on a blood sample or other tissues and can detect mutations in the mitochondrial DNA associated with hearing loss [9][11].
• Mitochondrial Nonsyndromic Hearing Loss and Deafness Mutation Panel: A specific genetic testing panel, known as the Mitochondrial Nonsyndromic Hearing Loss and Deafness Mutation Panel, is designed to assess 3 mitochondrial genes associated with hearing loss [7]. This panel can help identify mutations in these genes that may be causing the hearing loss.
• Gene Panels: Larger gene panels, such as a 138-gene panel or a 288-gene panel, are also available for assessing non-coding variants and the maternally inherited mitochondrial genome [4][8]. These panels can provide more comprehensive information about potential genetic causes of hearing loss.

Key Points

• Genetic testing is essential for diagnosing mitochondrial nonsyndromic sensorineural deafness.
• Specific gene panels, such as the Mitochondrial Nonsyndromic Hearing Loss and Deafness Mutation Panel, are available to assess genes associated with hearing loss.
• Larger gene panels can provide more comprehensive information about potential genetic causes of hearing loss.

References

[9] Diagnosis of non-syndromic mitochondrial hearing loss involves genetic testing to identify mutations in the mitochondrial DNA associated with hearing loss. [11] DIAGNOSIS/TESTING: The diagnosis of mitochondrial nonsyndromic hearing loss and deafness is established in a proband with hearing loss and identification of a pathogenic variant in MT-RNR1 or MT-TS1, or one of the eight additional mitochondrial genes known to cause nonsyndromic hearing loss and deafness. [7] The Mitochondrial Nonsyndromic Hearing Loss and Deafness Mutation Panel is designed to assess 3 mitochondrial genes associated with hearing loss. [4] A 138 gene panel that includes assessment of non-coding variants. In addition, it also includes the maternally inherited mitochondrial genome. [8] A 288 gene panel that includes assessment of non-coding variants and the maternally inherited mitochondrial genome.

Current Status of Drug Treatment for Mitochondrial Nonsyndromic Sensorineural Deafness

Unfortunately, there are currently no medications approved by the FDA to prevent or restore hearing loss associated with mitochondrial nonsyndromic sensorineural deafness [9]. However, researchers have been exploring various treatments to modulate mitochondrial dynamics and potentially treat hearing loss [6].

Aminoglycoside Ototoxicity

It's worth noting that certain individuals carrying pathogenic variants in the MT-RNR1 gene may be predisposed to severe and irreversible hearing loss after exposure to aminoglycoside antibiotics [8]. This highlights the importance of genetic counseling and careful consideration of antibiotic use in these individuals.

Emerging Therapies

While there are no approved treatments for mitochondrial nonsyndromic sensorineural deafness, researchers have identified potential therapeutic targets, including modulating mitochondrial dynamics. These emerging therapies hold promise for future treatment options [6].

Current Recommendations

In the absence of specific treatments, management of mitochondrial nonsyndromic sensorineural deafness typically involves a multidisciplinary approach, including rehabilitation strategies such as hearing aids, speech therapy, and culturally appropriate language training [2]. Cochlear implantation may also be considered in some cases [11].

References:

[6] Zou T. Drugs treat hearing loss by modulating mitochondrial dynamics. 2022; Cited by 10

[8] Carriers of the mutation who undergo even one course of aminoglycoside antibiotic therapy can suffer severe and irreversible loss of hearing. IV. Clinical ...

[9] Tan WJT. Unfortunately, to date, no clinically approved pharmacological treatments are available to prevent or restore other forms of hearing loss. However, a promising ... 2023; Cited by 37

[11] A review of cochlear implantation in mitochondrial sensorineural hearing loss. Otology and ...

Mitochondrial nonsyndromic sensorineural deafness can be challenging to diagnose, but there are several key factors to consider in the differential diagnosis.

Causes and Risk Factors

• Maternal Inheritance: Mitochondrial nonsyndromic sensorineural deafness is transmitted by maternal inheritance, meaning that it is passed down from mother to child. This is because only egg cells contribute mitochondria to the fertilized egg.
• Mitochondrial DNA (mtDNA) Mutations: The condition is caused by mutations in mitochondrial DNA (mtDNA), which are inherited from one's mother.

Differential Diagnosis

The differential diagnosis for mitochondrial nonsyndromic sensorineural deafness includes:

• Sensorineural Hearing Loss: This is a type of hearing loss that affects the inner ear and can be caused by various factors, including age-related hearing loss, exposure to loud noises, or certain medications.
• X-linked Hearing Loss: This is a rare form of hearing loss that is inherited in an X-linked pattern, meaning it is passed down from mother to son.
• Other Mitochondrial Disorders: Mitochondrial nonsyndromic sensorineural deafness can be part of a broader spectrum of mitochondrial disorders, which can affect multiple systems and organs.

Key Diagnostic Features

To diagnose mitochondrial nonsyndromic sensorineural deafness, the following key features should be considered:

• Sensorineural Hearing Loss: The presence of sensorineural hearing loss is a critical feature.
• Maternal Inheritance: A family history of maternal inheritance can provide important clues.
• Mitochondrial DNA (mtDNA) Mutations: Genetic testing for mtDNA mutations can confirm the diagnosis.

Diagnostic Tests

The following diagnostic tests may be used to diagnose mitochondrial nonsyndromic sensorineural deafness:

• Genetic Testing: This involves analyzing the patient's mitochondrial DNA for mutations.
• Audiological Evaluation: A thorough audiological evaluation is necessary to assess the extent and nature of the hearing loss.

References

1. [3] Non-syndromic mitochondrial sensorineural hearing loss is due to mutations in mitochondrial DNA (mtDNA) and is transmitted by maternal inheritance.
2. [4] Most forms of nonsyndromic hearing loss are described as sensorineural, with X-linked and mitochondrial forms being rare.
3. [6] Causative mitochondrial DNA (mtDNA) mutations have been found in 5–10% of patients with postlingual non-syndromic hearing loss.
4. [9] In cases of genetic HL; mitochondrial mutations are involved; where it is estimated to be the responsible mutation in causing approximately 5% of non-syndromic hearing loss.