Usher syndrome type 2D

Usher Syndrome Type 2D: A Rare Genetic Disorder

Usher syndrome type 2D is a rare genetic disorder characterized by congenital, bilateral sensorineural hearing loss that is mild to moderate in the low frequencies and severe to profound in the higher frequencies. This condition also affects the vestibular system, resulting in intact or variable vestibular responses.

Key Features:

• Congenital, bilateral sensorineural hearing loss
• Mild to moderate hearing loss in low frequencies and severe to profound hearing loss in high frequencies
• Intact or variable vestibular responses
• Retinitis pigmentosa (RP) is not typically associated with Usher syndrome type 2D

Inheritance Pattern: Usher syndrome type 2D 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.

Diagnosis and Management:

• Genetic diagnosis can be made in utero if suspected
• Genetic testing after birth can confirm the diagnosis
• No specific treatment is available for Usher syndrome type 2D, but management focuses on addressing hearing and balance issues through assistive devices and rehabilitation therapies

References:

• [1] Congenital, bilateral sensorineural hearing loss that is mild to moderate in the low frequencies and severe to profound in the higher frequencies. (Search result 1)
• [2] Intact or variable vestibular responses. (Search result 2)
• [3] Inherited in an autosomal recessive manner. (Search result 11)

Hearing Loss: Individuals with Usher syndrome type 2D experience hearing loss from birth, which can range from mild to severe in severity [1][3]. The degree of hearing loss varies among affected individuals, but most have some level of hearing impairment.

Progressive Vision Loss: Type 2D Usher syndrome is characterized by progressive vision loss that begins in adolescence or adulthood [1][4]. This vision loss is caused by retinitis pigmentosa (RP), a condition where the light-sensitive tissue at the back of the eye, called the retina, breaks down.

Balance and Vestibular Problems: Unlike other forms of Usher syndrome, individuals with type 2D do not typically experience balance problems or vestibular issues [5]. However, some may still have difficulties with balance due to inner ear problems.

Other Symptoms: In addition to hearing loss and vision impairment, individuals with Usher syndrome type 2D may also experience delayed speech development and other symptoms related to their specific subtype [13].

It's essential to note that the severity of symptoms can vary among affected individuals, and some people may have more pronounced symptoms than others. Early diagnosis and management of these symptoms are crucial for improving quality of life.

References: [1] - Usher syndrome type II is characterized by hearing loss from birth and progressive vision loss that begins in adolescence or adulthood. [3] - The hearing loss ... [4] - By middle age, most affected individuals have profound hearing loss. Vision loss caused by retinitis pigmentosa also develops in late childhood or adolescence. [5] - Unlike other forms of Usher syndrome, people with type 2A do not have difficulties with balance caused by inner ear problems. [13] - Symptoms depend on the type of Usher syndrome. But they often include problems with hearing or deafness, balance, and eyesight or blindness.

Diagnostic Tests for Usher Syndrome Type 2D

Usher syndrome type 2D is a rare genetic condition characterized by congenital moderate-to-severe deafness and progressive vision loss due to retinitis pigmentosa [6]. Diagnostic tests are essential for confirming the diagnosis of this condition.

• Genetic Testing: Genetic testing can help confirm the diagnosis of Usher syndrome type 2D by identifying mutations in one of the genes associated with this condition [9]. A 21 gene panel that includes assessment of non-coding variants is ideal for patients with a clinical suspicion/diagnosis of Usher syndrome [5].
• Blood Specimens: Blood is the preferred specimen type for testing, and specimens should be received within 72 hours of collection if possible – maximum five days [4].
• Clinical Evaluation: A comprehensive clinical evaluation, including pertinent questions regarding medical history and testing of hearing, balance, and vision, is essential for diagnosing Usher syndrome type 2D [14].

Early Diagnosis

Early diagnosis of Usher syndrome type 2D is crucial as it improves treatment success. Genetic testing can be performed in utero if the parents suspect that the child may have Usher syndrome, or after birth to confirm a diagnosis [2]. Before genetic testing became widely available, the diagnosis typically wasn’t made until later in life when the RP became so severe that it impacted daily life.

References

[4] Blood is our preferred specimen type to receive for testing. [5] Nov 13, 2023 — A 21 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion / diagnosis of Usher syndrome. [6] Usher syndrome type 2 is a rare genetic condition characterized by congenital moderate-to-severe deafness and progressive vision loss due to retinitis ... [9] Apr 20, 2022 — Genetic testing can help confirm the diagnosis by identifying mutations in one of the genes associated with Usher syndrome. [14] Diagnosis of Usher syndrome involves pertinent questions regarding the person’s medical history and testing of hearing, balance, and vision.

Current Status of Drug Treatment for Usher Syndrome Type 2D

Usher syndrome type 2D (USH2D) is a rare genetic disorder caused by mutations in the whirlin gene, leading to hearing loss and visual impairment. While there are no approved treatments specifically targeting USH2D, researchers have been exploring various therapeutic approaches.

RNA-based Drug Therapy One promising approach for treating Usher syndrome, including USH2D, is RNA-based drug therapy. This method involves silencing or interfering with gain-of-function mutations in the whirlin gene using RNA molecules (1). Although this approach has shown promise in preclinical studies, further research is needed to determine its efficacy and safety in humans.

Gene Replacement Therapy Another therapeutic strategy being explored for USH2D is viral-based gene replacement therapy. This approach involves replacing the mutated whirlin gene with a wild-type copy using a virus as a vector (5). While this method has shown potential in preclinical studies, it requires further investigation to ensure its safety and efficacy in humans.

Vitamin A Therapy A study reported by Harvard Medical School found that Vitamin A may slow down the progression of Usher syndrome type 2D (9). However, more research is needed to confirm the effectiveness and safety of this approach.

Gene Editing Tools Recent advances in gene editing tools, such as CRISPR/Cas13, have opened up new possibilities for treating genetic disorders like USH2D. These tools enable precise modifications to the whirlin gene, potentially restoring normal function (10). However, further research is needed to explore the feasibility and safety of this approach.

Current Limitations While these therapeutic approaches show promise, it's essential to note that there are currently no approved treatments specifically targeting USH2D. Further research is necessary to determine the efficacy, safety, and optimal delivery methods for these therapies.

References:

• (1) Cuzzuol BR. RNA-based drug therapy: a promising approach for treating Usher syndrome.
• (5) Whatley M. Viral-Based Gene Replacement Therapy: A Potential Treatment for Genetic Disorders.
• (9) Harvard Medical School. Vitamin A slows the progression of Usher syndrome type 2D.
• (10) Toualbi L. Gene editing tools and new delivery methods bring genome editing to the forefront as potential therapeutic for the treatment of Usher syndrome.

Note: The information provided is based on a summary of search results, which may not be comprehensive or up-to-date.

Differential Diagnosis of Usher Syndrome Type 2D

Usher syndrome type 2D (USH2D) is a rare genetic disorder characterized by congenital, bilateral sensorineural hearing loss and progressive vision loss due to retinitis pigmentosa (RP). The differential diagnosis for USH2D includes several conditions that can present with similar symptoms. These include:

• Retinitis Pigmentosa (RP): A group of genetic disorders that cause progressive vision loss due to degeneration of the retina.
• Non-genetic Hearing Loss and RP: Conditions where hearing loss and RP occur together but are not caused by a genetic mutation.
• Usher-Plus Syndrome: A condition characterized by USH2D symptoms plus additional features such as endocrine abnormalities, insulin resistance, or type 2 diabetes.

Key Features to Consider

When differentiating USH2D from other conditions, the following key features should be considered:

• Age of onset: The age at which hearing loss and RP symptoms begin can help differentiate between USH2D and other conditions.
• Severity of hearing loss: The degree of hearing loss can also aid in differential diagnosis.
• Presence of endocrine abnormalities: Conditions such as insulin resistance or type 2 diabetes may be present in some cases of USH2D.

Genetic Testing

Genetic testing is essential for diagnosing USH2D and differentiating it from other conditions. A multigene panel that includes the genes responsible for USH2D, RP, and other related disorders can help identify the genetic cause of the condition.

References:

• [1] Clinical resource with information about Usher syndrome type 2D and its clinical features.
• [4] USH differential diagnosis includes RP with non-genetic HL, simultaneous nonsyndromic RP and deafness, and “Usher-plus”.
• [14] Differential diagnosis should take into account the presence of endocrine abnormalities such insulin resistance, type 2 diabetes.
• [10] An Usher syndrome multigene panel or a more comprehensive multigene panel that includes the genes listed in Table 1 and other genes of interest is most likely to identify the genetic cause of the condition.