autosomal recessive nonsyndromic deafness 29

Autosomal Recessive Nonsyndromic Deafness 29 (DFNB29) is a form of non-syndromic sensorineural hearing loss caused by mutations in the CLDN14 gene on chromosome 21q22 [6]. It is characterized by prelingual onset with severe to profound, stable hearing loss [7][8][9].

This condition 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 [3][10]. The hearing loss associated with DFNB29 is typically present at birth or develops early in life and remains stable over time.

The CLDN14 gene plays a crucial role in maintaining the integrity of tight junctions between cells, which are essential for proper auditory function. Mutations in this gene can disrupt normal cellular interactions, leading to hearing impairment [4].

DFNB29 is a rare form of congenital deafness, and its exact prevalence is unknown. However, it has been identified in several consanguineous families worldwide, highlighting the importance of genetic testing for individuals with a family history of this condition.

References: [3] - A common way to classify nonsyndromic hearing loss is by the condition's pattern of inheritance: autosomal. [4] - The DFNB29 locus was initially mapped to chromosome 21q22.1 by linkage analysis in two large consanguineous Pakistani families segregating profound congenital deafness. [6] - Deafness, autosomal recessive 29 is a form of non-syndromic sensorineural hearing loss caused by mutations in the CLDN14 gene on chromosome 21q22. [7] - Definition: An autosomal recessive nonsyndromic deafness that is characterized by prelingual onset with severe to profound, stable hearing loss and ... [8] - Disease Ontology Definition:An autosomal recessive nonsyndromic deafness that is characterized by prelingual onset with severe to profound, stable hearing ... [9] - autosomal recessive deafness 29; DFNB29. Definition: An autosomal recessive nonsyndromic deafness that is characterized by prelingual onset with severe to ...

Autosomal recessive nonsyndromic deafness, also known as DFNB, is a type of hearing loss that is not associated with other signs and symptoms. The signs and symptoms of this condition are typically mild to moderate in severity.

• Bilateral hearing loss: Hearing loss affects both ears, and the degree of severity can range from mild to profound [5].
• Prelingual onset: The hearing loss usually occurs before a person learns to speak, which means it is present at birth or develops early in childhood [5].
• Sensorineural hearing loss: The type of hearing loss associated with autosomal recessive nonsyndromic deafness is sensorineural, meaning that the problem lies with the inner ear or the nerve pathways connecting the inner ear to the brain [5].

It's worth noting that individuals with autosomal recessive nonsyndromic deafness may not exhibit any other signs or symptoms beyond hearing loss. The condition is typically diagnosed through genetic testing and audiometric evaluation.

References: [5] - Autosomal recessive, Most common cause of mild to moderate autosomal recessive non-syndromic hearing loss. Prelingual, Sensorineural. Bilateral. Generally mild ... (Search result 5)

Autosomal Recessive Nonsyndromic Deafness (ARNSHL) can be diagnosed through various diagnostic tests.

• Newborn Screening: This test detects moderate to profound hearing loss, but may miss mild hearing loss. It is usually performed shortly after birth.
• Routine Screening within the School System: Regular hearing screenings are often conducted in schools for children who have not been previously identified with hearing loss.
• Genetic Testing: Genetic testing can be used to identify specific genetic mutations that cause ARNSHL. This includes testing for mutations in genes such as GJB2, GJB3, and GJB6 [1][2].
• Gene Panel Testing: A 138 gene panel is available that includes assessment of non-coding variants, as well as the maternally inherited mitochondrial genome [4].
• Targeted Familial Testing: This type of testing involves analyzing DNA samples from family members to identify specific genetic mutations that may be causing ARNSHL. The diagnostic yield for targeted familial testing was 60% in one study [9].

It's worth noting that a diagnosis of ARNSHL can also involve a combination of these tests, as well as clinical evaluation and medical history.

References: [1] Context result 2 [2] Context result 3 [4] Context result 4 [9] Context result 9

Understanding Non-Syndromic Hearing Loss

Non-syndromic hearing loss, also known as isolated hearing loss, is a type of hearing impairment that occurs without any other symptoms or signs. It is estimated to affect approximately 70% of cases of genetic hearing loss [5]. This condition can be caused by various factors, including genetic mutations.

Causes and Inheritance Patterns

The etiology of sensorineural hearing loss is heavily influenced by genetic mutations, with around 80% of cases attributed to genetic causes and only 20% to environmental factors [3]. Over 100 non-syndromic deafness genes have been identified in humans thus far. In non-syndromic sensorineural hearing impairment, approximately 75-85% of cases follow an autosomal recessive inheritance pattern [3].

Treatment Options

Current therapies for hearing loss are limited to hearing aids or cochlear implants. No biological therapies exist, and treatment is primarily aimed at attempting to restore hearing through these methods [7]. In some cases, treatment may be proposed for certain forms of conductive hearing loss.

Genetic Factors

Genetic factors play a critical role in at least 50% of cases of sensorineural hearing loss in healthy full-term neonates [10]. Hearing loss due to autosomal recessive transmission and autosomal dominant transmission occurs in approximately 80-90% and 10-20% of cases, respectively.

Conclusion

Non-syndromic hearing loss is a complex condition with various causes and inheritance patterns. While treatment options are limited, understanding the genetic factors involved can provide valuable insights into potential therapeutic approaches.

References:

[1] An interim analysis of a single-arm trial in 5 children with hereditary deafness shows that binaural AAV gene therapy is safe and leads to hearing improvement up to 13–26 weeks of follow-up. [3] The etiology of sensorineural hearing loss is heavily influenced by genetic mutations, with approximately 80% of cases attributed to genetic causes and only 20% to environmental factors. [5] These mutations account for about 70% of cases of genetic hearing loss. [7] Current therapies for hearing loss are hearing aids or cochlear implants. No biological therapies exist. [10] Hearing loss due to autosomal recessive transmission and autosomal dominant transmission occurs in approximately 80–90% and 10–20% of cases, respectively.

Autosomal recessive nonsyndromic deafness (ARNSHL) can be challenging to diagnose, but there are several factors that can help in making a differential diagnosis. Here are some key points to consider:

• Prelingual hearing loss: ARNSHL often presents with prelingual hearing loss, meaning the individual is born with significant hearing impairment or develops it before speech development [5].
• Bilateral involvement: The condition typically affects both ears, although unilateral cases can occur [7].
• Sensorineural hearing loss: ARNSHL is characterized by sensorineural hearing loss, which involves damage to the inner ear's sensory cells (hair cells) or the auditory nerve [9].
• Genetic inheritance: As a recessive condition, ARNSHL requires an individual to inherit two copies of the mutated gene (one from each parent) to express the condition [2].

When considering differential diagnoses for ARNSHL, it is essential to rule out other conditions that may present with similar symptoms. Some potential differentials include:

• Autosomal dominant nonsyndromic deafness: This condition can also cause hearing loss but typically presents later in life (postlingually) and may be associated with specific genetic mutations [8].
• X-linked recessive deafness: Although rare, X-linked recessive deafness can present with similar symptoms to ARNSHL, particularly in males who inherit the mutated gene from their mother [6].

To accurately diagnose ARNSHL, a comprehensive evaluation is necessary, including:

• Genetic testing: Identifying specific genetic mutations associated with ARNSHL, such as those affecting the GJB2 or OTOF genes.
• Audiological assessment: Conducting thorough hearing tests to determine the extent and nature of the hearing loss.
• Medical history: Reviewing the individual's medical history to identify any potential contributing factors.

By considering these factors and differentials, healthcare professionals can make an informed diagnosis and develop an effective treatment plan for individuals with autosomal recessive nonsyndromic deafness.