dentatorubral-pallidoluysian atrophy

Dentatorubral-Pallidoluysian Atrophy (DRPLA) Description

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder characterized by various combinations of involuntary movements, mental and emotional problems, cognitive decline, epilepsy, and ataxia.

Key Features:

• Involuntary movements, such as myoclonus and choreoathetosis [1]
• Mental and emotional problems, including dementia and psychiatric disturbance [3][6]
• Cognitive decline, affecting thinking ability [5]
• Epilepsy, a condition characterized by recurrent seizures [2][6]
• Ataxia, a loss of coordination and balance [9]

Causes:

DRPLA is caused by an expansion of a CAG repeat tract within the atrophin 1 gene, leading to a polyglutamine disorder [7]. This genetic mutation affects various parts of the brain, resulting in the characteristic symptoms of DRPLA.

References:

[1] - A rare subtype of autosomal dominant cerebellar ataxia type I characterized by involuntary movements, ataxia, epilepsy, mental disorders, cognitive decline [2] - by S Tsuji · 2012 · Cited by 96 — Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder clinically characterized by various combinations of ... [3] - Dec 5, 2023 — Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive brain disorder that causes involuntary movements, mental and emotional problems, ... [4] - Dentatorubral–pallidoluysian atrophy (DRPLA) is an autosomal dominant spinocerebellar degeneration caused by an expansion of a CAG repeat encoding a ... [5] - It can lead to involuntary movements, mental and emotional problems, and a decline in thinking ability. [6] - by LS Carroll · 2018 · Cited by 65 — Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, autosomal dominantly inherited disorder characterized by myoclonus, epilepsy, ataxia, and dementia. [7] - Dentatorubral-Pallidoluysian Atrophy is a polyglutamine disorder resulting from the expansion of a CAG repeat tract within the atrophin 1 gene. [8] - Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder with protean clinical manifestations consisting of ... [9] - DRPLA is a rare autosomal dominant neurodegenerative disorder characterized by ataxia, choreoathetosis, dementia, and psychiatric disturbance in adults.

Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive disorder that affects various parts of the brain, leading to a range of signs and symptoms. Here are some of the most common ones:

• Ataxia: This refers to a lack of coordination and balance, making it difficult to walk or perform other physical activities [1][3][6].
• Uncontrollable movements of the limbs (choreoathetosis): People with DRPLA may experience involuntary movements of their arms and legs, which can be quite pronounced [1][3][6].
• Psychiatric symptoms: Mood changes, depression, anxiety, and other psychiatric issues are common in individuals with DRPLA [1][6].
• Epilepsy: Seizures are a frequent occurrence in people with this condition [2][7][9].
• Myoclonus: This refers to sudden, brief muscle contractions that can be quite intense [4][7][9].
• Cognitive decline: As the disease progresses, individuals may experience memory loss, difficulty with problem-solving, and other cognitive impairments [2][8].
• Dementia: In advanced stages of DRPLA, people may develop dementia, which is a significant decline in cognitive function [8].

It's worth noting that the severity and progression of these symptoms can vary significantly from person to person.

Diagnostic Tests for Dentatorubral-Pallidoluysian Atrophy (DRPLA)

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder. Diagnostic tests are essential to confirm the diagnosis of DRPLA in symptomatic patients and for predictive testing in individuals with a family history of the disease.

Genetic Testing

• Polymerase Chain Reaction (PCR): Genetic testing typically involves PCR amplification across the ATN1 CAG repeat region, followed by gel or capillary electrophoresis [6]. This test is used to confirm the diagnosis of DRPLA and for presymptomatic detection of individuals at risk.
• CAG Repeat Length Analysis: The analysis of CAG repeat length is a reliable diagnostic test for DRPLA and is valuable for the presymptomatic detection of individuals at risk [15].

Clinical Diagnostic Criteria

• There are no clinical diagnostic criteria for dentatorubral-pallidoluysian atrophy. Clinical symptoms, family history, and ancestry can increase the yield of targeted molecular genetic testing [10].
• Age of Onset: The onset of DRPLA symptoms can occur at any age, ranging from infancy to late adulthood (range: age 0-72 years; mean: age 31.5 years) [11].

Imaging Studies

• Head Magnetic Resonance Imaging (MRI): Head MRI shows atrophy of cerebellum, brainstem, cerebrum, and high signal in periventricular white matter [5]. This imaging study can help support the diagnosis of DRPLA.

Other Diagnostic Tests

• There are no other specific diagnostic tests for DRPLA. A combination of clinical evaluation, family history, and genetic testing is essential to confirm the diagnosis.

References: [5] - Context 5 [6] - Context 6 [10] - Context 10 [11] - Context 11 [15] - Context 15

Treatment Options for Dentatorubral-Pallidoluysian Atrophy (DRPLA)

While there is no specific treatment for DRPLA, various therapeutic approaches can help manage its symptoms. Here are some key points to consider:

• Standard Antiepileptic Drugs (AEDs): Patients with epilepsy require standard AED treatment to control seizures [5].
• Avoid Phenytoin: This medication should be avoided as it may worsen the condition [6].
• Olanzapine: In some cases, olanzapine has been effective in treating psychotic symptoms associated with DRPLA [2][3].
• First-Generation Antipsychotics (FGAs): FGAs like haloperidol and levomepromazine have also shown effectiveness in managing symptoms [4].

Experimental Therapeutic Approaches

• Antisense Oligonucleotides (ASOs): Researchers are exploring the use of ASOs, such as n-Lorem's experimental ASO specific for DRPLA, which may potentially reduce abnormal protein levels and provide a therapeutic benefit [1].
• Disease-Modifying Therapies: Although no disease-modifying therapies are currently available for inherited ataxias like DRPLA, researchers are investigating various strategies to develop such treatments in the future [8].

Current Management

The current management of DRPLA involves treating its symptoms, including seizures and mental health issues. While these approaches can help improve quality of life, they do not address the underlying cause of the condition.

References:

[1] n-Lorem's experimental ASO for DRPLA [2] Olanzapine treatment for psychotic symptoms in DRPLA [3] First-generation antipsychotics for symptom management [4] Standard AED treatment for epilepsy [5] Avoiding phenytoin due to potential worsening of the condition [6] Current management of DRPLA involves treating its symptoms

Differential Diagnosis of Dentatorubral-Pallidoluysian Atrophy (DRPLA)

Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive neurologic disorder that can be challenging to diagnose due to its similarities with other conditions. The differential diagnosis for DRPLA includes:

• Multiple System Atrophy: A neurodegenerative disorder characterized by autonomic dysfunction, parkinsonism, and cerebellar ataxia [4].
• Huntington's Disease (HD): An autosomal dominant inherited disorder that causes progressive damage to the brain, leading to cognitive decline, motor dysfunction, and psychiatric symptoms [8].
• Spinocerebellar Ataxias: A group of genetic disorders that affect coordination, balance, and speech, often accompanied by other neurological symptoms [8].

In juvenile cases with Progressive Myoclonic Epilepsy (PME), conditions such as mitochondrial disease should also be considered in the differential diagnosis [5].

Genetic Testing for Confirmation

Diagnosis of DRPLA can be confirmed through genetic testing, which involves analyzing a blood sample to identify the presence of the DRPLA gene mutation [7].