autosomal dominant nonsyndromic deafness 6

Autosomal dominant nonsyndromic deafness 6 (DFNA6) is a form of hearing loss that affects individuals with no other symptoms or syndromes associated with it. This type of hearing loss is caused by heterozygous mutations in the WFS1 gene on chromosome 4p16 [3][11].

The characteristics of autosomal dominant nonsyndromic deafness 6 are heterogeneous, but in most cases, hearing loss tends to be bilateral and post-lingual, meaning it occurs after language development has taken place [7]. The severity of hearing loss can range from mild to profound, with varying degrees of impact on an individual's daily life.

In terms of the specific characteristics of this type of deafness, autosomal dominant nonsyndromic deafness 6 is characterized by prelingual onset and low frequency progressive hearing loss [10]. This means that individuals affected by this condition typically experience hearing loss before they develop language skills, and it tends to progress over time.

It's worth noting that these mutations account for about 70% of cases of genetic hearing loss [4], making autosomal dominant nonsyndromic deafness 6 a significant contributor to inherited hearing impairments.

Autosomal dominant nonsyndromic deafness, also known as DFNA hearing loss, can be characterized by the following signs and symptoms:

• Progressive postlingual deafness: This form of deafness typically starts after language development has taken place, leading to a gradual decline in hearing ability.
• Severe attacks of vertigo: Some individuals with autosomal dominant nonsyndromic deafness may experience severe episodes of dizziness or vertigo.
• Subjective tinnitus: A sensation of ringing or other sounds in the ear can be present in some cases.

It's worth noting that these symptoms can vary in severity and presentation from person to person, even within the same family. The COCH gene mutations associated with autosomal dominant nonsyndromic deafness can lead to a range of hearing loss severities, from mild to profound.

References:

• [2] - This form of deafness is always associated with malformations of the inner ear that can be detected by CT scan.
• [9] - DFNA2 nonsyndromic hearing loss is characterized by symmetric, predominantly high-frequency sensorineural hearing loss (SNHL) that is progressive across all ages.

Autosomal dominant nonsyndromic deafness 6 (ADND6) is a genetic disorder that affects hearing and is inherited in an autosomal dominant pattern. Diagnostic tests for ADND6 are crucial for accurate diagnosis and management of the condition.

Genetic Testing

Genetic testing is the primary diagnostic tool for ADND6. The WFS1 gene, located on chromosome 4p16.1, is associated with ADND6. Sequence analysis of the entire coding region of the WFS1 gene can help identify mutations that cause the condition [5][11].

Clinical Genetic Test

A comprehensive clinical genetic test offered by Intergen for conditions (1) includes testing for ADND6. This test evaluates the presence of mutations in the WFS1 gene and other genes associated with autosomal dominant nonsyndromic hearing loss [5].

Next-Generation Sequencing (NGS)

NGS, also known as massively parallel sequencing (MPS), is a genetic testing method that can detect mutations in multiple genes simultaneously. This approach has been used to identify novel autosomal dominant NSHL genes and may be useful for diagnosing ADND6 [13].

Clinical Molecular Genetics Test

A clinical molecular genetics test offered by LifeLabs Genetics includes sequence analysis of the entire coding region, NGS/MPS with CNV detection included, specifically for ADND6. This test can help identify mutations in the WFS1 gene and other genes associated with autosomal dominant nonsyndromic hearing loss [11].

References

• Comprehensive genetic screening of KCNQ4 in a large autosomal dominant nonsyndromic hearing loss cohort: genotype-phenotype correlations and a founder mutation. [5]
• Clinical Genetic Test offered by Intergen for conditions (1): Autosomal dominant nonsyndromic hearing loss 6; Testing genes (1): WFS1 (4p16.1); [5]
• Clinical Molecular Genetics test for Autosomal dominant nonsyndromic hearing loss 6 and using Sequence analysis of the entire coding region, Next-Generation (NGS)/Massively parallel sequencing (MPS) with CNV detection included offered by LifeLabs Genetics. [11]

Differential Diagnosis of Autosomal Dominant Nonsyndromic Deafness

Autosomal dominant nonsyndromic deafness (ADNSHL) is a type of hearing loss that can be inherited in an autosomal dominant pattern. The differential diagnosis for ADNSHL involves identifying the underlying genetic cause, which can be challenging due to the complexity of the condition.

Key Points:

• COCH gene mutations: Mutations in the COCH gene are associated with progressive postlingual deafness and severe attacks of vertigo [6].
• Other genes involved: At least 30 genes have been identified as causing ADNSHL, including MYO6 (DFNA22) and TECTA (DFNA8/12), which account for a significant proportion of cases in Europe [2].
• Clinical features: ADNSHL is typically postlingual, progressive, and high frequency, with exceptions and distinctive features associated with selected genes [11].

Genetic Considerations:

• Autosomal dominant inheritance: ADNSHL follows an autosomal dominant pattern, meaning that only one copy of the mutated gene is necessary to express the phenotype.
• De novo mutations: De novo mutations should be considered in all cases of negative family history.

Diagnostic Approach:

• Genetic testing: Genetic testing for specific genes associated with ADNSHL can help identify the underlying cause.
• Family history: A thorough family history is essential to determine the inheritance pattern and potential genetic causes.
• Clinical evaluation: A comprehensive clinical evaluation, including audiologic assessment and medical history, is necessary to rule out other conditions that may mimic ADNSHL.

References:

[2] - Autosomal dominant non-syndromic HL does not have a single identifiable gene responsible for the majority of cases worldwide [1]. [6] - Mutations in the COCH gene result in progressive postlingual deafness associated with severe attacks of vertigo [6]. [11] - Exceptions to the generalization and/or distinctive features associated with selected genes are summarized in Table 4 [11].