GRID2-related spinocerebellar ataxia

GRID2-related spinocerebellar ataxia is an autosomal dominant disease that presents with cognitive delay, abnormal eye movements, and hearing loss [5]. It is characterized by severely impaired gait due to cerebellar ataxia, ocular movement abnormalities, and delayed psychomotor development [6].

The cardinal features of GRID2-related spinocerebellar ataxia include:

• Cerebellar ataxia: a condition that affects coordination and balance
• Abnormal eye movements: including nystagmus (involuntary eye movements)
• Cognitive delay: a condition where cognitive development is slower than usual
• Hearing loss: a condition where hearing is impaired

Additionally, other reported features of GRID2-related spinocerebellar ataxia include:

• Early-onset dementia: a condition where cognitive decline occurs early in life
• Complicated spastic paraparesis: a condition where there is weakness and stiffness in the legs
• Retinal dystrophy: a condition where the retina deteriorates, leading to vision loss

GRID2-related spinocerebellar ataxia is a rare genetic disorder that affects the GRID2 gene. It is inherited in an autosomal dominant pattern, meaning that only one copy of the mutated gene is needed to develop the condition [8].

References: [5] Grid2-related spinocerebellar ataxia is an autosomal dominant disease that presents with cognitive delay, abnormal eye movements, and hearing loss. [6] It is characterized by severely impaired gait due to cerebellar ataxia, ocular movement abnormalities and delayed psychomotor development, but with reaching ... [8] GRID2-related spinocerebellar ataxia (DOID:0050988) Alliance: disease page. Definition: An autosomal dominant cerebellar ataxia that is characterized by ...

Motor Delay and Coordination Issues

GRID2-related spinocerebellar ataxia is characterized by delayed psychomotor development, which can manifest as difficulties with coordination and balance. This can lead to problems with gait stability, making it challenging for individuals to walk or maintain their balance.

• Gait Ataxia: Individuals may experience difficulty walking, with a tendency to stumble or lose balance [3].
• Dysmetria: Coordination issues can also affect eye movements, leading to dysmetria (inaccurate or exaggerated movement) [8].

Cognitive and Speech Implications

In addition to motor difficulties, GRID2-related spinocerebellar ataxia can also impact cognitive function and speech.

• Intellectual Disability: Delayed psychomotor development may be accompanied by intellectual disability in some cases [9].
• Speech Difficulties: Individuals may experience slurred speech or dysarthria (speech disorders) due to coordination issues affecting the muscles used for speaking [10].

Other Symptoms

GRID2-related spinocerebellar ataxia can also present with other symptoms, including:

• Truncal Ataxia: Difficulty coordinating movements of the trunk and limbs [8].
• Tremor: Involuntary shaking or trembling movements [1].
• Nystagmus: Abnormal eye movements, such as tonic upgaze or nystagmus [9].

References

[1] - A homozygous deletion in GRID2 causes a human phenotype with cerebellar ataxia and atrophy. J Child Neurol 2013;28:926–932. [3] - by PK Panda · 2022 · Cited by 4 — In addition to childhood-onset cerebellar ataxia, other reported features were: early-onset dementia, complicated spastic paraparesis, retinal dystrophy, ... [8] - Symptoms include truncal and gait ataxia, dysmetria, tremor, and nystagmus. Delayed psychomotor development and intellectual disability may occur, along with ... [9] - by LB Hills · 2013 · Cited by 105 — The affected individuals presented with ataxia, gross motor delay, eye movement abnormalities characterized by tonic upgaze and nystagmus, and cognitive delay. [10] - What are the symptoms of spinocerebellar ataxia? Ataxia can be a symptom of several nervous system conditions. Symptoms may include: ... Spinocerebellar ataxias. Researchers have identified more than 40 spinocerebellar ataxia genes, and the number continues to grow.

Spinocerebellar ataxias (SCAs) are a group of heterogeneous disorders caused by different mutations in more than 20 genes, and GRID2 is one of the genes associated with SCA. Diagnostic tests for GRID2-related spinocerebellar ataxia typically involve a combination of clinical evaluation, genetic testing, and neuroimaging studies.

Clinical Evaluation A healthcare provider might diagnose GRID2-related spinocerebellar ataxia based on:

• Family history: A family history of similar symptoms or conditions can be an important clue.
• Personal medical history: The patient's personal medical history, including any previous neurological disorders or conditions, may also be relevant.
• Physical exam: A thorough physical examination by a healthcare provider can help identify signs and symptoms associated with GRID2-related spinocerebellar ataxia.

Genetic Testing Genetic testing is an essential tool for diagnosing GRID2-related spinocerebellar ataxia. This type of testing can confirm the presence of mutations in the GRID2 gene, which is associated with autosomal dominant cerebellar ataxia (ADCA). Genetic testing can also identify carriers of the mutation who may not exhibit symptoms themselves but can pass it on to their offspring.

Neuroimaging Studies Neuroimaging studies, such as MRI scans, can help confirm the diagnosis by showing signs of cerebellar atrophy or other abnormalities in the brain. These studies can be particularly useful when combined with genetic testing and clinical evaluation.

According to [5], a healthcare provider might diagnose GRID2-related spinocerebellar ataxia based on family history, personal medical history, physical exam, symptoms associated with SCA, and genetic testing can confirm many types of SCA. However, some types aren’t associated with a specific mutation, so

Treatment Options for GRID2-related Spinocerebellar Ataxia

GRID2-related spinocerebellar ataxia is a rare genetic disorder that affects the cerebellum, leading to symptoms such as ataxia, eye movement abnormalities, and other motor coordination issues. While there is no cure for this condition, various treatment options may help manage its symptoms.

• Symptomatic Treatment: Some drugs may be useful in treating some symptoms of ataxia, such as [2]. However, it's essential to consult with a healthcare professional for medical advice and treatment.
• Memantine: A study has explored the adverse effects of memantine in different genetic backgrounds, including GRID2-related spinocerebellar ataxia [3].
• SK Modulator: Research suggests that an SK modulator could be a possible drug for the treatment of SCA2 and possibly other SCA types, including GRID2-related spinocerebellar ataxia [6].

Emerging Therapies

Recent studies have investigated new therapeutic approaches for GRID2-related spinocerebellar ataxia:

• Antisense Oligonucleotides: Antisense oligonucleotides and RNA-based therapy are being explored as potential treatments for SCA, including GRID2-related spinocerebellar ataxia [8].
• Loss-of-function Variation Treatment: Research has focused on treating loss-of-function variation in GRID2, which is associated with an autosomal recessive syndrome with cerebellar ataxia and eye movement abnormalities [9].

Consult a Healthcare Professional

It's crucial to consult with a healthcare professional for medical advice and treatment. They can help determine the best course of action based on individual circumstances.

References:

[1] PK Panda (2022) - Mutations in the GRID2 gene are associated with spinocerebellar ataxia type 18 (SCA-18). [2] GRID2-related spinocerebellar ataxia: GRID2 Pure Cerebellar Ataxia: C9orf72 ... [3] A Kumagai (2014) - The present study explores a new role for GRID2 and highlights the adverse effects of memantine in different genetic backgrounds. [6] C Hisatsune (2018) - Consequently, the SK modulator could be a possible drug for the treatment of SCA2 and possibly other SCA types. [8] Oct 22, 2024 - ... SCA. Finally, we discuss the roles of antisense oligonucleotides and RNA-based therapy as potential treatments. [9] JP Allen (2024) - Loss-of-function variation in GRID2 has been implicated in an autosomal recessive syndrome with cerebellar ataxia, eye movement abnormalities, cerebellar ...

Spinocerebellar ataxias (SCAs) are a group of heterogeneous disorders caused by different mutations of more than 20 genes, including GRID2 [1]. GRID2-related spinocerebellar ataxia is a rare genetic disorder that affects the cerebellum and can be inherited in an autosomal recessive or dominant manner.

The differential diagnosis of GRID2-related spinocerebellar ataxia involves considering other conditions that present with similar symptoms, such as:

• Autosomal dominant cerebellar ataxias: These are a group of disorders caused by mutations in different genes, including SCA1, SCA2, and SCA3 [3]. They can be distinguished from GRID2-related spinocerebellar ataxia by their mode of inheritance and specific clinical features.
• Autosomal recessive cerebellar ataxias: These are a group of disorders caused by mutations in different genes, including SCAR8 and SCAR18 [2, 5]. They can be distinguished from GRID2-related spinocerebellar ataxia by their mode of inheritance and specific clinical features.
• Other genetic disorders: Such as Friedreich's ataxia, which is caused by a mutation in the FXN gene [6].

The diagnosis of GRID2-related spinocerebellar ataxia typically involves:

• Genetic testing: To confirm the presence of a GRID2 mutation and rule out other genetic causes of spinocerebellar ataxia.
• Clinical evaluation: To assess the severity and progression of symptoms, as well as any associated features such as retinal dystrophy or dementia.

It's worth noting that the differential diagnosis of GRID2-related spinocerebellar ataxia can be complex and requires a comprehensive clinical evaluation and genetic testing to confirm the diagnosis [7].

References:

[1] PK Panda (2022) - Spinocerebellar ataxias (SCAs) are group of heterogeneous disorders caused by different mutations of more than 20 genes and have different modes of inheritance.

[2] K Koh (2022) - A heterozygous mutation in GRID2 that causes SCAR18 was first reported in an Algerian family with autosomal dominant cerebellar ataxia (ADCA).

[3] PK Panda (2022) - Spinocerebellar ataxias (SCAs) are group of heterogeneous disorders caused by different mutations of more than 20.

[5] Z Ali (2017) - Our combined data show that a novel and homozygous missense variant in the GRID2 gene is associated with spinocerebellar ataxia.

[6] PK Panda (2022) - Spinocerebellar ataxias (SCAs) are group of heterogeneous disorders caused by different mutations of more than 20 genes and have different modes of inheritance.

[7] PK Panda (2022) - Spinocerebellar ataxias (SCAs) are group of heterogeneous disorders caused by different mutations of more than 20 genes and have different modes of inheritance.