autosomal recessive nonsyndromic deafness 112

Autosomal Recessive Nonsyndromic Deafness 112 (DFNB112) is a form of non-syndromic, sensorineural deafness characterized by postlingual progressive hearing impairment. This means that the hearing loss occurs after language development and progresses over time.

• Cause: DFNB112 results from damage to the neural structures in the inner ear, leading to sensorineural hearing loss (SNHL) [4].
• Inheritance: It is inherited in an autosomal recessive pattern, meaning that both copies of the gene in each cell have mutations. Each parent typically carries one copy of the mutated gene but does not have hearing loss themselves [11].
• Prevalence: The exact prevalence of DFNB112 is unknown, but it is considered a rare form of non-syndromic deafness.
• Genetic basis: Mutations in the BDP1 gene (607012) on chromosome 5q13 are associated with this condition [10].

It's worth noting that autosomal recessive nonsyndromic deafness 112 is one of several forms of non-syndromic hearing loss, which constitutes about 75% of all hearing loss cases. The genetic basis for these conditions can be complex and involve multiple genes.

Autosomal recessive nonsyndromic deafness 112 (DFNB112) is characterized by postlingual progressive sensorineural hearing impairment [3]. The symptoms of this condition typically include:

• Progressive hearing loss: Hearing impairment that worsens over time, often starting in adulthood or later childhood.
• Sensorineural hearing loss: Damage to the inner ear or auditory nerve, leading to difficulty hearing sounds, especially high-frequency sounds.
• Postlingual onset: Hearing loss occurs after language development has taken place, meaning individuals with DFNB112 may have developed speech and language skills before experiencing significant hearing impairment.

It's essential to note that the symptoms of autosomal recessive nonsyndromic deafness 112 can vary in severity and progression among affected individuals [5].

Based on the provided context, here are some diagnostic tests for autosomal recessive nonsyndromic deafness:

• Genetic testing: This is the single best diagnostic test in the evaluation of hearing loss, with a diagnostic rate of ~40% (1). Comprehensive genetic testing can identify mutations in genes responsible for autosomal recessive nonsyndromic deafness.
• GJB2 gene panel: The GJB2 gene encoding the gap junction protein connexin 26 is a common cause of autosomal recessive nonsyndromic hearing loss, accounting for an estimated 50% of all cases (13). A GJB2 gene panel can be used to diagnose this condition.
• 288 gene panel: This panel includes assessment of non-coding variants and the maternally inherited mitochondrial genome, making it a useful tool for diagnosing autosomal recessive nonsyndromic deafness (6).
• Autosomal recessive hearing loss gene panels: These panels can be used to identify mutations in genes responsible for autosomal recessive nonsyndromic deafness, such as the TECTA gene (11).

It's worth noting that the diagnosis of autosomal recessive nonsyndromic deafness often requires a combination of clinical evaluation and genetic testing. A comprehensive analysis of deafness genes can be used to establish a diagnosis in families with this condition (14).

Autosomal recessive nonsyndromic deafness (ARNSHL) is a type of hearing loss that occurs when there is a mutation in one of the genes responsible for hearing, and an individual inherits two copies of the mutated gene, one from each parent.

Current Treatment Options:

Unfortunately, there are no specific drug treatments available to treat autosomal recessive nonsyndromic deafness. However, researchers have been exploring various treatment options, including:

• Gene therapy: This involves using a virus to deliver a healthy copy of the gene to the inner ear, where it can produce functional proteins and restore hearing.
• Hearing aids: These devices can amplify sound and help individuals with ARNSHL communicate more effectively.
• Cochlear implants: These are medical devices that bypass damaged or non-functioning parts of the ear and directly stimulate the auditory nerve, allowing individuals to perceive sound.

Emerging Therapies:

Researchers have been investigating various emerging therapies for treating autosomal recessive nonsyndromic deafness, including:

• Stem cell therapy: This involves using stem cells to regenerate or repair damaged inner ear tissue.
• Gene editing technologies: These include CRISPR-Cas9 and other gene editing tools that can be used to correct genetic mutations responsible for ARNSHL.

Challenges and Future Directions:

While these emerging therapies hold promise, there are still significant challenges to overcome before they can be translated into effective treatments. These include:

• Safety concerns: Gene therapy and stem cell therapy carry risks of adverse reactions and unintended consequences.
• Efficiency: Current gene editing technologies may not be efficient enough to correct genetic mutations responsible for ARNSHL.

Conclusion:

While there are no specific drug treatments available for autosomal recessive nonsyndromic deafness, researchers are actively exploring various emerging therapies that hold promise for restoring hearing in individuals with this condition. Further research is needed to overcome the challenges associated with these therapies and translate them into effective treatments.

References:

• [1] Smith RJH (2018) - Most persons with DFNA2 nonsyndromic hearing loss are first fitted with hearing aids to assist with sound amplification between ages ten and 40.
• [5-13] Notably, in clinical trials of gene therapy for treating autosomal recessive deafness 9 (DFNB9), the patients' hearing was recovered without evident adverse reactions.
• [14-16] Nevertheless, numerous challenges persist in using gene therapy for treating deafness due to the intricate structure of the cochlea.

The differential diagnosis of autosomal recessive nonsyndromic deafness (ARNSHL) involves identifying the underlying genetic cause of hearing loss in individuals with this condition.

According to various studies, including [13], the differential diagnosis of ARNSHL can be challenging due to its complex genetic basis. However, several genes have been implicated in causing ARNSHL, and a comprehensive diagnostic approach is essential to identify the specific genetic mutation responsible for the condition.

Some of the key factors to consider in the differential diagnosis of ARNSHL include:

• Genetic testing: Genetic testing can help identify mutations in one of the 42 genes associated with ARNSHL. This can be done through targeted gene sequencing or whole-exome sequencing.
• Family history: A thorough family history is essential to determine if there is a pattern of inheritance consistent with autosomal recessive transmission.
• Clinical evaluation: A comprehensive clinical evaluation, including a detailed medical and hearing loss history, is necessary to rule out other potential causes of hearing loss.

In terms of specific genes associated with ARNSHL, [14] notes that more than 700 different mutations have been identified in one of the 42 genes implicated in this condition. Some of the key genes include:

• GJB2: Mutations in the GJB2 gene on chromosome 13q12 are a common cause of ARNSHL.
• TECTA: Missense mutations in the TECTA gene have been associated with autosomal recessive non-syndromic HL (DFNB21).
• CABP2: A mutation in the CABP2 gene at the DFNB93 locus has been reported to cause autosomal-recessive nonsyndromic deafness.

Overall, a multidisciplinary approach involving genetic testing, family history evaluation, and clinical assessment is essential for accurate differential diagnosis of ARNSHL.