autosomal recessive nonsyndromic deafness 79

Autosomal Recessive Nonsyndromic Deafness 79 (ARND79) is a type of hearing impairment that affects one or both ears, caused by an abnormal functioning of the cochlear nerve. It is a progressive form of sensorineural hearing loss [1].

This condition is characterized by severe to profound, stable hearing loss, typically with onset before speech development (prelingual deafness) [6][9]. The symptoms are limited to hearing impairment, without any vestibular dysfunction.

ARND79 is often associated with mutations in the TPRN gene, which is responsible for encoding a protein involved in the regulation of cochlear function. This genetic mutation leads to the degeneration of sensory hair cells in the inner ear, resulting in permanent hearing loss [4][5].

According to clinical resources, ARND79 can be diagnosed through genetic testing, which is available in the US and other countries. The condition is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to express the condition [2][10].

Autosomal recessive nonsyndromic deafness, also known as DFNB, is a type of hearing loss that occurs when there are mutations in both copies of a gene. The signs and symptoms of this condition can vary among individuals, but they typically include:

• Hearing loss: This is the primary symptom of autosomal recessive nonsyndromic deafness. It can range from mild to severe and may be unilateral (in one ear) or bilateral (in both ears).
• Early-onset hearing loss: In many cases, the hearing loss associated with autosomal recessive nonsyndromic deafness begins in early childhood, often before the age of 5.
• Bilateral involvement: Both ears are usually affected, although there may be some asymmetry between the two ears.

According to [11], GJB2-related autosomal recessive nonsyndromic hearing loss is the most common genetic cause of congenital severe-to-profound non-progressive sensorineural hearing loss in many world populations. In countries where available, newborn hearing screening (NBHS) typically identifies severe-to-profound hearing loss.

It's worth noting that [12] states that nonsyndromic hearing loss can be classified in several different ways, and one common way is by the condition's pattern of inheritance: autosomal dominant (DFNA), autosomal recessive (DFNB), X-linked (DFNX), or mitochondrial. However, autosomal recessive nonsyndromic deafness specifically refers to a type of hearing loss that occurs due to mutations in both copies of a gene.

In contrast, syndromic hearing loss occurs with signs and symptoms affecting other parts of the body [12].

Autosomal Recessive Nonsyndromic Deafness (ARNSD) is a genetic condition that affects hearing, and diagnostic tests play a crucial role in its identification. Here are some key points related to the diagnostic tests for ARNSD:

• Genetic testing: Molecular genetic testing is available for many types of syndromic and nonsyndromic deafness, including ARNSD [8]. This test can identify mutations in genes associated with hearing loss.
• GJB2 gene testing: The GJB2 gene is the most common cause of congenital severe-to-profound non-progressive sensorineural hearing loss. Genetic testing for the GJB2 gene can help establish a diagnosis of ARNSD [10].
• Parental carrier testing: If there's a family history of ARNSD, parental carrier testing should be offered to confirm that parents are carriers and that the risk of passing on the condition is higher [7].
• Prenatal cfDNA screening: Prenatal cfDNA screening can detect fetal genotypes for autosomal recessive non-syndromic hearing loss with a high degree of accuracy, with concordance rates varying depending on parental genotypes and fetal variants [14].

It's essential to note that the diagnosis of ARNSD is established in a proband (an individual with the condition) with suggestive findings and confirmed by genetic testing. A comprehensive analysis of deafness genes in families with autosomal recessive nonsyndromic hearing loss can also provide valuable information for diagnosis [12].

References: [7] - Parental carrier testing should be offered, where relevant, to confirm that parents are carriers and that the risk of passing on the condition is higher. [8] - Molecular genetic testing plays a crucial role in diagnosing syndromic and nonsyndromic deafness, including ARNSD. [10] - Genetic testing for the GJB2 gene can help establish a diagnosis of ARNSD. [12] - Comprehensive analysis of deafness genes in families with autosomal recessive nonsyndromic hearing loss can provide valuable information for diagnosis. [14] - Prenatal cfDNA screening can detect fetal genotypes for autosomal recessive non-syndromic hearing loss with a high degree of accuracy.

Autosomal recessive nonsyndromic deafness, also known as DFNB type, accounts for approximately 85% of cases of non-syndromic hearing loss. As of my knowledge cutoff in 2024, there is no specific drug treatment available for autosomal recessive nonsyndromic deafness.

However, researchers are exploring various gene therapy approaches to treat this condition. For example, a study published in 2024 demonstrated the effectiveness of AAV1-hOTOF gene therapy in treating hereditary deafness [2]. This approach involves using a viral vector (AAV) to deliver a healthy copy of the OTOF gene to the inner ear, which can help restore hearing.

Additionally, cochlear implants or hearing aids are currently the most common treatment options for individuals with autosomal recessive nonsyndromic deafness. These devices can significantly improve communication and quality of life for those affected by this condition [5].

It's essential to note that gene therapy is still an emerging field, and more research is needed to fully understand its potential benefits and limitations in treating autosomal recessive nonsyndromic deafness.

References: [2] Wang H. Gene therapy is a promising approach for hereditary deafness. (2024) [5] Jiang L. To date, more than 150 deafness genes have been recognized to be associated with HHL. Current clinical treatments for HHL are cochlear implants or hearing aids... (2023)

Autosomal recessive nonsyndromic deafness (ARNSHL) can be challenging to diagnose, and a differential diagnosis is often necessary to rule out other conditions that may present with similar symptoms. Here are some key points to consider:

• GJB2-related ARNSHL: This is the most common genetic cause of congenital severe-to-profound hearing loss. It 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.
• OTOF-related ANSD: This condition is characterized by congenital or prelingual severe-to-profound bilateral deafness without inner-ear anomalies on MRI or CT scans. It is also inherited in an autosomal recessive pattern.
• Other genetic causes: There are several other genes that can cause ARNSHL, including TMIE, which is associated with a mutation that affects all frequencies and leads to profound hearing loss.

When considering a differential diagnosis for ARNSHL, it's essential to rule out other conditions that may present with similar symptoms. These include:

• Congenital infections: Certain congenital infections, such as rubella or cytomegalovirus, can cause hearing loss.
• Inner-ear anomalies: While OTOF-related ANSD does not typically have inner-ear anomalies on imaging studies, other conditions may present with structural abnormalities in the inner ear.
• Neurological disorders: Certain neurological disorders, such as Usher syndrome or Charcot-Marie-Tooth disease, can cause hearing loss.

To make an accurate diagnosis and differential diagnosis of ARNSHL, a comprehensive evaluation is necessary. This should include:

• Genetic testing: Genetic testing for GJB2, OTOF, TMIE, and other relevant genes can help identify the underlying cause of the hearing loss.
• Imaging studies: Imaging studies, such as MRI or CT scans, can help rule out inner-ear anomalies or other structural abnormalities.
• Medical history: A thorough medical history is essential to rule out congenital infections or other conditions that may have contributed to the hearing loss.

By considering these factors and performing a comprehensive evaluation, healthcare providers can make an accurate diagnosis and differential diagnosis of ARNSHL.