X-linked deafness 2

X-linked deafness-2 (DFNX2), also known as conductive deafness with stapes fixation (DFN3), is a rare genetic disorder that affects hearing and is linked to the X chromosome.

Characteristics:

• Progressive mixed hearing loss: DFNX2 is characterized by progressive conductive and sensorineural hearing loss, which means that both the outer and inner ear are affected.
• Pathognomonic temporal bone deformity: A distinctive temporal bone deformity is a hallmark of this disorder, featuring dilatation of the inner auditory canal and a fistulous connection between the internal auditory canal and the cochlear basal turn.
• Perilymphatic fluid 'gusher' during stapes surgery: During surgical procedures on the stapes, a perilymphatic fluid 'gusher' may occur due to the abnormal connection between the inner ear structures.

Clinical Features:

• Hypoplasia of cochlea: The cochlea is underdeveloped in individuals with DFNX2.
• Enlarged internal acoustic canal: The internal auditory canal is enlarged, which can lead to complications during surgery.
• Stapes fixation: The stapes bone is fixed in place, leading to conductive hearing loss.

Prevalence:

• X-linked deafness-2 accounts for approximately 5% of all cases of congenital deafness and affects males more frequently than females due to its X-linked recessive inheritance pattern.

These characteristics and features are based on the information provided in search results [1, 4, 6, 9, 11, 12, 14].

X-linked deafness 2 (DFNX2), also known as DFN3, is an X-linked recessive disorder characterized by progressive conductive and sensorineural hearing loss.

Clinical Features:

• Hypoplasia of cochlea: The cochlea, a spiral-shaped structure in the inner ear responsible for sound processing, is underdeveloped or absent.
• Enlarged internal acoustic canal: The internal auditory meatus, a canal that connects the inner ear to the brain, is abnormally large.
• Stapes gusher upon surgery and stapes fixation: During surgical procedures involving the middle ear, a fluid "gusher" may occur due to an abnormal connection between the internal auditory canal and the cochlear basal turn. Additionally, the stapes bone, one of the three bones in the middle ear responsible for transmitting sound vibrations, is fixed or abnormally positioned.

These clinical features are characteristic of X-linked deafness 2 (DFNX2) and can be used to diagnose this condition.

References:

• [10] states that the most frequent clinical features of DFNX2 in affected males are hypoplasia of cochlea, enlarged internal acoustic canal, and a characteristic stapes gusher upon surgery and stapes fixation.
• [12] describes DFNX2 as an X-linked recessive disorder characterized by progressive conductive and

Diagnostic Tests for X-linked Deafness 2 (DFNX2)

X-linked deafness 2, also known as DFNX2 or DFN3, is an X-linked recessive disorder characterized by progressive conductive and sensorineural hearing loss. The diagnostic tests for this condition are crucial in confirming the diagnosis and providing a clear understanding of the genetic basis of the disease.

Recommended Diagnostic Tests:

• POU3F4 gene test: This test is recommended for individuals who present with bilateral, progressive, mixed, X-linked hearing loss [3]. It involves quantitative testing to detect large deletions using MLPA (Multiplex Ligation-dependent Probe Amplification) [5].
• Genetic testing: Genetic testing can be performed to identify the POU3F4 gene mutation associated with DFNX2. This test is essential in confirming the diagnosis and providing a clear understanding of the genetic basis of the disease [7].

Other Relevant Information:

• Fragile X testing (FMR1 sequencing) and GJB2/GJB6 sequencing were performed using standard molecular techniques, but these tests are not specifically recommended for DFNX2 [2].
• A 288 gene panel that includes assessment of non-coding variants is also available, which may be useful in identifying other genetic causes of hearing loss [9].

References:

[1] Not applicable (this information was not provided in the context)

[2] The individual should have completed otologic and audiologic tests, as well as ancillary testing such as CT imaging of the inner ear to determine the ... (context 1)

[3] Any individual who presents with bilateral, progressive, mixed, X-linked hearing loss can be offered the POU3F4 gene test. (context 3)

[5] Quantitative testing of the POU3F4 gene to detect large deletions using MLPA (Multiplex Ligation-dependent Probe Amplification). (context 5)

[7] Knowledge on rare diseases and orphan drugs · Search for a diagnostic test · Molecular diagnosis of X-linked Deafness type 2 and 4 (POU3F4 and SMPX gene). (context 7)

Based on the provided context, it appears that there are limited treatment options available for X-linked deafness type 2 (DFNX2), a rare form of non-syndromic genetic deafness.

• Currently, there is no FDA-approved drug to treat hereditary deafness, including X-linked deafness type 2 [5].
• Treatment for hearing loss in general is focused on minimizing or overcoming secondary effects of hearing loss, rather than addressing the underlying cause [7].
• Gene therapy has been explored as a potential treatment approach for hereditary deafness, but it is still in its early stages and not yet widely available [4, 6].

However, research suggests that gene therapy may hold promise for treating X-linked deafness type 2. A study published by H Wang et al. in 2024 reported on the use of unilateral AAV1-hOTOF gene therapy with dual promoters to restore hearing in a mouse model of DFNX2 [6]. While this is an encouraging finding, further research is needed to confirm its efficacy and safety in humans.

It's worth noting that X-linked deafness type 2 is caused by mutations in the POU3F4 gene, which accounts for nearly 50% of all cases of X-linked hearing loss [8]. Further studies are required to develop effective treatments for this condition.

References: [5] Jan 24, 2024 — There are currently no FDA-approved drugs to help with hereditary deafness, which has opened the door for new solutions like gene therapies. In ... [6] by H Wang · 2024 · Cited by 12 — Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual ... [7] Aug 31, 2022 — No biological therapies exist. Treatment basically is an attempt to minimize/overcome secondary effects of hearing loss. [8] by J Defourny · 2022 · Cited by 1 — X-linked deafness type 2 (DFNX2, locus Xq21.1), caused by POU3F4 mutations, accounts for nearly 50% of all cases of X-linked hearing loss.

The differential diagnosis for X-linked deafness 2 (DFNX2) involves considering other conditions that may present with similar symptoms, such as sensorineural hearing loss and temporal bone deformity.

• Otosclerosis: This is a condition where there is abnormal bone growth in the middle ear, leading to conductive hearing loss. However, it can be differentiated from DFNX2 through imaging studies, such as computed tomography (CT) scans [9].
• Large vestibular aqueduct syndrome: This is another inner ear developmental disorder that may present with sensorineural hearing loss and other symptoms similar to DFNX2.
• Cochlear incomplete partition type III (IP-III): This is a rare inner ear malformation characterized by an abnormally wide opening in the bone separating the basal turn of the cochlea from the internal auditory canal, which can be associated with DFNX2 [7].
• Other developmental disorders: Various other conditions affecting the inner ear may need to be ruled out through differential diagnosis.

It's essential to note that a comprehensive evaluation by an audiologist or otolaryngologist is necessary to accurately diagnose and differentiate X-linked deafness 2 from these other conditions.