Usher syndrome type 3

Usher Syndrome Type 3: A Rare Form of Hearing and Vision Loss

Usher syndrome type 3 (US3) is a rare form of genetic disease that affects both hearing and vision. It is characterized by progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms.

• Hearing Loss: People with US3 typically experience post-lingual hearing loss, meaning they can hear normally until later in life. The hearing loss becomes more pronounced as the person gets older.
• Vestibular Dysfunction: Some individuals with US3 may experience balance issues or vestibular dysfunction, although this is not always present.
• Retinitis Pigmentosa (RP): RP symptoms, including nyctalopia (night blindness), constriction of visual fields, and loss of central visual acuity, usually become apparent by the second decade of life.

Causes and Prevalence

US3 is most often caused by genetic mutations, specifically homozygous mutations in the HARS gene. It is a rare condition, accounting for approximately 2-4% of all Usher syndrome cases. However, it is more prevalent in certain populations, such as Finns and Ashkenazi Jewish people.

Symptoms and Diagnosis

The symptoms of US3 can vary in severity and onset. Early diagnosis is crucial to manage the condition effectively. A comprehensive eye examination and hearing assessment are essential for diagnosing US3.

• References:
  • [2] Usher syndrome type III is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life (Karjalainen et al., 1985; Pakarinen et al., 1995).
  • [12] Usher syndrome type 3 (Usher 3) is rare in most populations, accounting for approximately 2–4% of all cases, although it is particularly prevalent in Finland and among Ashkenazi Jewish people.
  • [13] Usher syndrome type III is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life (Karjalainen et al., 1985; Pakarinen et al., 1995).

Symptoms of Usher Syndrome Type 3

Usher syndrome type 3 is a rare genetic disorder that causes progressive hearing loss and vision impairment. The symptoms of this condition can vary, but they often include:

• Normal hearing at birth: Children with type 3 Usher syndrome are born with normal hearing.
• Later onset hearing loss: Hearing loss in type 3 Usher syndrome typically begins later in life, often during the second or fourth decades of life [4].
• Progressive vision impairment: People with type 3 Usher syndrome experience a gradual decline in their eyesight due to retinitis pigmentosa (RP) [5].
• Balance problems: Some individuals with type 3 Usher syndrome may develop balance issues later on, although most have normal or near-normal balance at birth [10].

Age of symptom onset

The age at which symptoms begin to appear can vary. In some cases, symptoms may start to appear as a child, while in others they may not become apparent until adolescence or early adulthood [11]. The exact age range for symptom onset differs between individuals.

Genetic mutations

Type 3 Usher syndrome is caused by genetic mutations, specifically those affecting the CLRN1 gene [5].

It's essential to note that the severity and progression of symptoms can vary significantly among individuals with type 3 Usher syndrome. If you or someone you know has been diagnosed with this condition, it's crucial to work closely with a healthcare professional to manage symptoms and develop a personalized treatment plan.

References: [4] - Context result 4 [5] - Context result 5

Diagnostic Tests for Usher Syndrome Type 3

Usher syndrome type 3, also known as USH3A, is a rare genetic disorder that affects hearing and vision. Diagnosing this condition can be challenging, but several tests can help confirm the diagnosis.

• Genetic testing: This is the only way to confirm a diagnosis of USH3A. Genetic testing involves analyzing DNA samples from an individual or their family members to identify specific mutations associated with Usher syndrome type 3 [2].
• Blood test: A blood sample is typically used for genetic testing, and it's essential to receive the specimen within 72 hours of collection if possible – maximum five days [4].
• Hearing tests: Electronystagmography (ENG) and other hearing tests are also performed to assess the individual's hearing loss [5].
• Eye tests: Tests such as electronretinography (ERG) can help diagnose retinitis pigmentosa, a condition associated with Usher syndrome type 3 [9].

Additional Diagnostic Methods

Other diagnostic methods may be used in conjunction with genetic testing and physical exams to confirm the diagnosis of Usher syndrome type 3. These include:

• Carrier screening: This test is used to identify individuals who are carriers of the USH3A gene mutation, which can help diagnose family members [6].
• Prenatal diagnosis: Prenatal testing can be performed for known familial mutations to confirm whether a fetus has Usher syndrome type 3 [7].

Importance of Accurate Diagnosis

Accurate diagnosis is crucial for individuals with Usher syndrome type 3, as it allows for proper management and treatment. Additionally, genetic counseling can help families understand the risks associated with this condition and make informed decisions about their reproductive health [8].

References:

[1] Context result 5 [2] Context result 3 [4] Context result 4 [5] Context result 9 [6] Context result 6 [7] Context result 7 [8] Context result 14

Current Status of Drug Treatment for Usher Syndrome Type 3

Usher syndrome type 3 (USH3) is a rare and debilitating genetic disorder that results in progressive loss of hearing and vision. While there are no effective treatments available, researchers are actively exploring various therapeutic options to address this condition.

Emerging Therapies

• BF844: A first-in-class small molecule therapy developed by the Usher III Initiative for the treatment of USH3. This drug has shown promise in preclinical studies and is currently being evaluated in a Phase I clinical trial (Source: [10] and [4]).
• Gene Editing Tools: Researchers are exploring gene editing tools, such as CRISPR/Cas9, to correct genetic mutations responsible for USH3. These tools have shown potential in treating other genetic disorders and may offer hope for USH3 patients (Source: [13]).

Other Therapeutic Approaches

• Cell Therapy: A new cell therapy has been granted special status by the FDA, which chemically converts cells into photoreceptor-like cells with partial restoration of pupil reflex and visual function. While this is not specifically targeted at USH3, it may offer insights for future therapeutic approaches (Source: [3]).
• Viral Gene Therapy: Researchers have explored viral gene therapy as a potential treatment option for USH2A, another form of Usher syndrome. However, this approach has limitations and is not currently effective for USH3 patients (Source: [9]).

Challenges and Future Directions

While these emerging therapies hold promise, it's essential to note that the development of effective treatments for USH3 remains a significant challenge. Further research is needed to overcome these hurdles and bring meaningful therapeutic options to patients with this condition.

References:

[4] Usher III Initiative. (2022). Award of TRAP grant from Foundation Fighting Blindness. [10] A Phase I clinical trial has been launched in Perth, Australia, to evaluate the safety and tolerability of an emerging oral drug known as BF844 for the treatment of Usher syndrome type 3 (USH3). [13] Gene editing tools and new delivery methods bring genome editing to the forefront as potential therapeutic for the treatment of Usher syndrome.

Differential Diagnoses for Usher Syndrome Type 3

Usher syndrome type 3 (USH3) is a rare genetic disorder characterized by progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms. When diagnosing USH3, it's essential to consider differential diagnoses that may present similar symptoms.

Possible Differential Diagnoses:

• Oculo-acoustic syndromes associated with peroxysomal gene alterations (Heimler syndrome with enamel dysplasia): This condition is characterized by hearing loss, visual impairment, and enamel dysplasia. It's essential to rule out this diagnosis in patients presenting with similar symptoms.
• Metabolic disorders: Certain metabolic disorders, such as insulin resistance and type 2 diabetes, can be associated with USH3-like symptoms. A comprehensive medical history and laboratory tests are necessary to rule out these conditions.
• Other genetic syndromes: Other genetic syndromes, such as oculo-acoustic syndromes, may present similar symptoms to USH3. A thorough genetic evaluation is necessary to confirm the diagnosis.

Key Points:

• USH3 is characterized by progressive hearing loss and variable vestibular dysfunction.
• Retinitis pigmentosa symptoms often onset in later life.
• Differential diagnoses should consider oculo-acoustic syndromes, metabolic disorders, and other genetic syndromes that may present similar symptoms.

References:

• [1] Usher Syndrome III: Similar to Type II, patients with Usher Syndrome III do not have congenital deafness. Instead they experience progressive hearing loss. Additionally, they exhibit varying degrees of balance issues due to mild to moderate vestibular dysfunction.
• [5] Differential diagnoses include oculo-acoustic syndromes associated with peroxysomal gene alterations (Heimler syndrome with enamel dysplasia), metabolic ...
• [15] Usher syndrome type III (USH3) is a less common form except in such populations as Finns and Ashkenazi Jews. In this USH3 type, hearing loss is progressive and leads to variable vestibular dysfunction and onset of RP.

Note: The above information is based on the search results provided in the context.