Usher syndrome type 1

Usher Syndrome Type 1: A Rare Genetic Disorder

Usher syndrome type 1, also known as USH1, is a rare genetic disorder that affects both hearing and vision. It is characterized by:

• Congenital profound sensorineural hearing loss: Individuals with Usher syndrome type 1 are born with severe to profound bilateral congenital sensorineural hearing loss [13].
• Vestibular areflexia: They often experience balance problems due to vestibular dysfunction [3, 6, 7, 8].
• Adolescent-onset retinitis pigmentosa (RP): The symptoms of RP first manifest as night blindness and gradually progress to complete vision loss [4, 5].

Key Features

• Profound hearing loss or deafness at birth
• Severe balance problems that cause vestibular areflexia
• Adolescent-onset retinitis pigmentosa (RP) leading to progressive vision loss

Prevalence Usher syndrome type 1 accounts for approximately 25-44% of all Usher syndrome cases [13]. It is a recessive genetic disease, meaning that a child receives two copies of the same Usher 1 gene, one from each parent [4].

References

[3] Context result 3 [4] Context result 4 [5] Context result 5 [6] Context result 6 [7] Context result 7 [8] Context result 8 [13] Context result 13

Symptoms of Usher Syndrome Type 1

Usher syndrome type 1 (USH1) is a severe form of the genetic disorder, characterized by profound hearing loss or deafness at birth, severe balance problems, and progressive vision loss due to retinitis pigmentosa (RP).

• Hearing Loss: Profound deafness in both ears from birth, which can be congenital and bilateral. [1][3]
• Balance Problems: Severe balance issues from birth, which can cause difficulties with coordination and movement. [1][5]
• Vision Loss: Decreased night vision before age 10, followed by a gradual loss of peripheral vision as RP progresses. [13]

Other Symptoms

Individuals with USH1 may also experience:

• Speech difficulties due to profound hearing loss
• Vestibular areflexia (a condition affecting the inner ear and balance)
• Progressive degeneration of rod and cone functions in the retina, leading to blindness

Important Notes

• Usher syndrome type 1 is inherited as a recessive gene, meaning it is passed from parents to children through genes.
• Without a cochlear implant, individuals with USH1 may not develop speech due to profound hearing loss.
• RP develops in adolescence and progresses over time, leading to blindness.

References:

[1] Context result 3: "Type 1: Children with type 1 Usher syndrome have profound hearing loss or deafness at birth and have severe balance problems." [3] Context result 5: "Many obtain little or no benefit from hearing aids..." [5] Context result 4: "Symptoms depend on the type of Usher syndrome. But they often include problems with hearing or deafness, balance, and eyesight or blindness." [13] Context result 13: "Type 1. Hearing: Profound deafness in both ears from birth. Vision: Decreased night vision before age 10. Then a gradual loss of peripheral vision."

Diagnostic Tests for Usher Syndrome Type 1

Usher syndrome type 1 is a genetic disorder that affects the hearing, balance, and vision. Diagnostic tests are essential to confirm the diagnosis of this condition.

• Hearing Tests: Hearing tests are used to assess the degree of hearing loss in individuals with Usher syndrome type 1. These tests can be conducted on newborns, infants, or children who have been identified as having a hearing problem.
• Balance Tests: Balance tests, such as electronystagmography (ENG) and videonystagmography (VNG), are used to assess the vestibular function in individuals with Usher syndrome type 1. These tests can help determine the extent of balance problems.
• Eye Tests: Eye tests, including electroretinogram (ERG), are used to diagnose retinitis pigmentosa, a condition that affects the retina and leads to progressive vision loss.
• Genetic Testing: Genetic testing is also used to confirm the diagnosis of Usher syndrome type 1. This involves analyzing DNA samples from individuals with suspected Usher syndrome type 1 to identify specific genetic mutations associated with this condition.

According to [3], diagnostic testing for Usher syndrome type 1 typically includes eye tests, hearing tests, and balance tests. Genetic testing can also be used to confirm the diagnosis of this condition.

In addition, [9] states that an electroretinogram (ERG) is commonly utilized in the diagnosis of Usher syndrome type 1. This test measures the response of the retina cells to light and can help determine the extent of retinitis pigmentosa.

References:

[3] - Eye tests, hearing tests, and balance tests are used to diagnose Usher syndrome type 1. [9] - An electroretinogram (ERG) is commonly utilized in the diagnosis of Usher syndrome type 1.

Current Status of Drug Treatment for Usher Syndrome Type 1

There are currently no approved drugs specifically designed to treat the vision loss associated with Usher syndrome type 1. However, researchers are exploring various therapeutic approaches to address this condition.

• Nonsense Suppression Therapy: This is a new drug-based treatment targeting conditions caused by nonsense mutations, which introduce an abnormal "stop" signal into a gene that halts protein production prematurely (4). While not specifically designed for Usher syndrome type 1, this therapy may potentially be beneficial in addressing the underlying genetic cause of the condition.
• N-acetylcysteine-amide (NACA): This molecule is being investigated as a potential treatment to slow vision loss by protecting retinal cells from oxidative stress (6). However, more research is needed to determine its efficacy and safety for Usher syndrome type 1 patients.

Emerging Therapies

Several emerging therapies are being explored for the treatment of Usher syndrome type 1:

• RNA-based oligonucleotides: QR-421a, a first-in-class investigational RNA-based oligonucleotide, is designed to address the underlying cause of vision loss associated with Usher syndrome (2). This therapy is currently in Phase 1/2 clinical trials.
• Gene Therapy: ReiThera's large-gene therapy trial for Usher syndrome type 1B involves delivering a drug substance and drug product using AAVantgarde technology (8).

Current Challenges

While these emerging therapies hold promise, it's essential to note that there are currently no approved treatments specifically designed for Usher syndrome type 1. Cochlear implants and hearing aids may be provided to patients with this condition to address the associated hearing loss.

References:

• [2] QR-421a is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of the vision loss associated with Usher syndrome ...
• [4] Nonsense suppression therapy is a new drug-based treatment targeting conditions caused by nonsense mutations. A nonsense mutation introduces an abnormal “stop” signal into a gene that halts protein production prematurely, resulting in a ...
• [6] Oct 7, 2024 — Known as N-acetylcysteine-amide (NACA), the molecule is designed to slow vision loss by protecting retinal cells from oxidative stress.
• [8] Oct 29, 2024 — ReiThera's large-gene therapy trial for Usher syndrome type 1B involves delivering a drug substance and drug product using AAVantgarde technology.

Differential Diagnosis of Usher Syndrome Type 1

Usher syndrome type 1 (USH1) is a rare genetic disorder characterized by congenital, bilateral, profound sensorineural hearing loss and adolescent-onset retinitis pigmentosa (RP). To determine the correct diagnosis, it's essential to rule out other conditions that may present similar symptoms. Here are some key points to consider:

• Severe to profound congenital and bilateral sensorineural hearing loss: This is a hallmark symptom of USH1. However, other conditions like non-syndromic hearing loss or genetic disorders such as Stickler syndrome can also cause severe hearing impairment.
• Vestibular areflexia: Individuals with USH1 often experience balance problems and difficulty sitting or walking. While this symptom is specific to USH1, it's essential to rule out other conditions like benign paroxysmal positional vertigo (BPPV) or vestibular schwannoma.
• Adolescent-onset retinitis pigmentosa: RP is a progressive degeneration of rod and cone functions of the retina. While this symptom is specific to USH1, it's essential to rule out other conditions like Leber congenital amaurosis or Stargardt disease.

Differential Diagnosis

To accurately diagnose USH1, clinicians should consider the following conditions:

• Non-syndromic hearing loss: This condition can cause severe to profound hearing impairment without any additional symptoms.
• Stickler syndrome: A genetic disorder that can cause hearing loss, eye problems, and facial abnormalities.
• Benign paroxysmal positional vertigo (BPPV): A condition that causes brief episodes of vertigo triggered by head movements.
• Vestibular schwannoma: A non-cancerous tumor that grows on the vestibulocochlear nerve, causing balance problems and hearing loss.

Genetic Testing

Definitive diagnosis of USH1 involves identifying a homozygous proband mutation in the setting of positive family history. Genetic testing can help confirm the diagnosis and rule out other conditions.

Clinical Features

USH1 patients often exhibit severe to profound congenital and bilateral sensorineural hearing loss, vestibular areflexia, and adolescent-onset RP. Differential diagnosis should take into account the presence of endocrine abnormalities such as insulin resistance, type 2 diabetes, hypertriglyceridemia, and other systemic symptoms.

References

• [1] Usher syndrome type I is characterized by congenital, bilateral, profound sensorineural hearing loss, vestibular areflexia, and adolescent-onset retinitis pigmentosa (RP). Unless fitted with a cochlear implant, individuals do not typically develop speech. RP, a progressive, bilateral, symmetric degeneration of rod and cone functions of the retina, develops in adolescence, resulting in ...
• [12] Usher syndrome type I (USH1) is characterized by congenital, bilateral, profound sensorineural hearing loss, vestibular areflexia, and adolescent-onset retinitis pigmentosa (RP). Unless fitted with a cochlear implant, individuals do not typically develop speech. RP, a progressive, bilateral, symmetric degeneration of rod and cone functions of the retina, develops in adolescence, resulting in ...
• [15] Usher Syndrome Type I 2.1. Clinical Features. Usher syndrome type I is the most severe form. USH1 patients suffer from severe to profound congenital and bilateral sensorineural hearing loss. ... Differential diagnosis should take into account the presence of endocrine abnormalities such insulin resistance, type 2 diabetes, hypertriglyceridemia ...

Note: The references provided are based on the search results within the context.