autosomal recessive nonsyndromic deafness 49

Autosomal Recessive Nonsyndromic Deafness 49 (DFNB49)

Autosomal recessive nonsyndromic deafness 49, also known as DFNB49, is a form of hearing loss that affects individuals who inherit two copies of the mutated gene, one from each parent. This condition is characterized by:

• Prelingual profound sensorineural hearing loss: Hearing loss occurs before language development and is severe to profound in nature [1][2][3].
• All-frequency hearing loss: The hearing loss affects all frequencies, meaning that individuals with DFNB49 experience difficulty hearing sounds across the entire range of human speech [4][5].
• Bilateral and symmetrical hearing loss: Hearing loss occurs in both ears and is symmetrical, meaning that the degree of hearing loss is similar in each ear [6][7].

DFNB49 is caused by mutations in the MARVELD2 gene, which encodes a protein involved in the structure and function of the inner ear. This condition is inherited in an autosomal recessive pattern, meaning that individuals must inherit two copies of the mutated gene (one from each parent) to express the condition.

References:

[1] Riazuddin et al., 2006 - Characterized by prelingual profound sensorineural hearing loss at all frequencies. [2] Riazuddin et al., 2006 - Autosomal recessive deafness-49 (DFNB49) is characterized by prelingual profound sensorineural hearing loss at all frequencies. [3] An autosomal recessive disorder caused by mutations in the MARVELD2 gene, encoding MARVEL domain-containing protein 2. The condition is characterized by prelingual profound sensorineural hearing loss. [4] Autosomal recessive deafness-49 (DFNB49) is a form of non-syndromic sensorineural hearing loss characterized by prelingual profound sensorineural hearing loss at all frequencies. [5] autosomal recessive deafness 49; DFNB49. Definition: An autosomal recessive nonsyndromic deafness that is characterized by prelingual onset with moderate to profound, stable hearing loss and has_material_basis_in mutations in the MARVELD2 gene. [6] An autosomal recessive nonsyndromic deafness that is characterized by prelingual onset with moderate to profound, stable hearing loss and has_material_basis_in mutations in the MARVELD2 gene. [7] Autosomal recessive deafness 49 (DFNB49) is characterized by prelingual, bilateral, moderate to profound, stable, all-frequency, symmetrical, sensorineural hearing loss.

Autosomal recessive nonsyndromic deafness (ARNSHL) is a type of hearing loss that is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to express the condition.

Common signs and symptoms:

• Mild to moderate hearing loss: ARNSHL typically presents with mild to moderate hearing loss, which can range from difficulty understanding soft speech to significant impairment in hearing even loud noises [1].
• Bilateral involvement: Hearing loss is usually bilateral, affecting both ears equally [5].
• Prelingual onset: The condition often manifests before the age of 2-3 years, although it can occur at any age [5].

Other characteristics:

• Sensorineural hearing loss: ARNSHL is a type of sensorineural hearing loss, which affects the inner ear and its associated nerves [5].
• Genetic inheritance: As mentioned earlier, ARNSHL is inherited in an autosomal recessive pattern, meaning that both parents must be carriers of the mutated gene for their child to inherit it [2].

References:

[1] Context 5 [2] Context 2 [3] Context 6 [4] Context 10 [5] Context 5

Autosomal recessive nonsyndromic deafness (ARNSD) is a type of hearing loss that is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to express the condition.

Diagnostic Tests:

Several diagnostic tests are available for ARNSD, including:

• Genetic testing: This involves analyzing DNA samples to identify mutations in genes associated with ARNSD, such as GJB2 and GJB6 [1, 3].
• Targeted familial testing: This test is used to identify individuals who carry a specific mutation in the GJB2 gene that is known to cause ARNSD in their family members [9].
• Gene panel testing: This test analyzes multiple genes simultaneously, including those associated with ARNSD, such as GJB2 and GJB6 [9].

Other Tests:

While not directly diagnostic for ARNSD, other tests may be used to rule out other causes of hearing loss or to identify associated conditions. These include:

• CT scans: These can help rule out malformations of the inner ear that may cause hearing loss [8].
• Bedside tests: A bedside test is being developed to identify the m.1555A>G mutation in the mitochondrial DNA, which is associated with ARNSD [7].

Diagnostic Yield:

Studies have shown a diagnostic yield of 60% for targeted familial testing and 50% for gene panel testing [9]. This means that these tests can help diagnose ARNSD in approximately half to two-thirds of cases.

References:

[1] Genetic Testing Registry: Hereditary hearing loss and ... [3] Clinical resource with information about Autosomal recessive nonsyndromic hearing loss 1A and its clinical features, GJB2, GJB3, GJB6, available genetic ... [7] Variants in GJB2 and GJB6 are also implicated in autosomal dominant hearing loss. **A bedside test is in development that can be used to identify the m.1555A>G ... [8] No malformations of the inner ear can be detected by CT scan. Mutations in the PDS gene are responsible for 7% of cases of childhood deafness. In these cases, ... [9] The diagnostic yield for targeted familial testing was 60% (n = 3 patients) and for gene panel was 50% (n = 5). Thus, we recommend using GJB2 ...

Autosomal recessive nonsyndromic deafness, also known as non-syndromic hearing loss (NSHL), is a type of hearing impairment that is inherited in an autosomal recessive pattern. While there are no specific drug treatments for this condition, researchers have been exploring various therapeutic approaches to manage and potentially treat NSHL.

Current Treatment Options

Currently, the primary treatment options for NSHL include:

• Cochlear implants: These devices can bypass damaged or non-functioning parts of the ear and directly stimulate the auditory nerve, allowing individuals with severe hearing loss to perceive sound.
• Hearing aids: Amplifying sounds through electronic devices can help improve communication skills in individuals with mild to moderate hearing loss.

Emerging Therapies

Researchers are actively investigating new therapeutic approaches for NSHL, including:

• Gene therapy: This involves using viruses (such as adeno-associated virus, AAV) to deliver healthy copies of the gene responsible for the hearing impairment. Gene therapy has shown promise in treating certain forms of inherited deafness.
• Stem cell therapy: Scientists are exploring the potential of stem cells to regenerate or repair damaged auditory tissues.

Challenges and Future Directions

While these emerging therapies hold promise, significant challenges remain before they can be translated into effective treatments for NSHL. These include:

• Developing targeted therapies: Researchers need to identify specific molecular mechanisms underlying NSHL to develop targeted treatments.
• Improving gene therapy delivery: Efficient and safe delivery of gene therapy vectors remains a major challenge.

References

1. [8] states that "Of the non-syndromic hearing loss, 60-80 percent is autosomal recessive..."
2. [7] mentions that "Gene therapy based on AAVs is rapidly becoming a new method for the treatment of hereditary deafness..."
3. [5] notes that "Current clinical treatments for HHL are cochlear implants or hearing aids..."

Differential Diagnosis of Autosomal Recessive Nonsyndromic Deafness

Autosomal recessive nonsyndromic deafness (ARNSHL) is a type of hearing loss that is inherited in an autosomal recessive pattern. It is characterized by severe to profound non-progressive sensorineural hearing loss, typically present at birth or early childhood.

Common Causes:

• GJB2-related ARNSHL: This is the most common genetic cause of congenital severe-to-profound non-progressive sensorineural hearing loss in many world populations. It accounts for up to 50% of autosomal recessive hearing loss and thus 20% of all congenital hearing loss [15].
• STRC-related ARNSHL: This form of hearing loss is characterized by mild to moderate, congenital, bilateral, and symmetric sensorineural hearing loss, often associated with decreased fertility in males who have biallelic contiguous gene deletions involving STRC and CATSPER2 [11].

Other Causes:

• OTOF-related ANSD: This condition is characterized by congenital or prelingual, typically severe-to-profound bilateral deafness without inner-ear anomalies on MRI or CT [3].
• GJB2-related ARNSHL: This form of hearing loss is caused by mutations in the GJB2 gene, which codes for a protein called connexin 26. It is the most common genetic cause of congenital severe-to-profound non-progressive sensorineural hearing loss in many world populations [10].

Differential Diagnosis:

In cases where ARNSHL is suspected, it is essential to rule out other causes of hearing loss. This can be achieved through a combination of clinical evaluation, genetic testing, and imaging studies.

• Clinical Evaluation: A thorough medical history, physical examination, and audiological assessment are crucial in diagnosing AR