Perry syndrome

Perry Syndrome: A Rare Progressive Brain Disease

Perry syndrome is a rare and progressive brain disease characterized by four major features:

• Parkinsonism: a pattern of movement abnormalities, including akinesia (inability to initiate changes in activity), muscular rigidity, and chorea (widespread involuntary movements)
• Psychiatric changes: depression, lethargy, withdrawal, apathy, and changes in character
• Weight loss: significant weight loss due to decreased appetite and metabolism
• Hypoventilation: abnormally slow breathing

These symptoms typically appear in a person's forties or fifties. The disease is progressive, meaning it worsens over time.

Age of Onset and Disease Duration

The mean age of onset for Perry syndrome is 48 years (range: 35-61), with the mean disease duration being five years (range: 2-14 years).

Inheritance Pattern

Perry syndrome is an autosomal dominant neurodegenerative disorder, meaning that a single copy of the mutated gene is enough to cause the condition. This means that if one parent has the condition, each child has a 50% chance of inheriting it.

References:

• [1] Description from search result 2
• [2-5] Symptoms and characteristics from search results 2, 4, 11, and 12
• [6-9] Inheritance pattern and disease duration from search results 5, 7, 8, and 9

Perry Syndrome Signs and Symptoms

Perry syndrome is a progressive brain disease characterized by four major features:

• Parkinsonism: This includes symptoms such as slow movements (bradykinesia), stiffness, and tremors. These movement abnormalities are often accompanied by changes in mood and cognitive function.
• Psychiatric Changes: Patients with Perry syndrome may experience depression, apathy, social withdrawal, and suicidal thoughts.
• Weight Loss: Severe weight loss is a common feature of the disease, particularly in its later stages.
• Abnormally Slow Breathing (Hypoventilation): This is a late feature of the disease, often appearing towards the end of the five-year average duration.

These signs and symptoms typically appear in a person's forties or fifties. As the disease progresses, patients may become bedridden or wheelchair-bound due to severe motor impairment [1][2][3].

Additional Symptoms

Other symptoms associated with Perry syndrome include:

• Insomnia
• Central hypoventilation (slow breathing)
• Marked autonomic dysfunction

These symptoms can vary in severity and duration among individuals, but they are all characteristic of the disease [4][5][6].

References: [1] Context 1: Perry syndrome is a progressive brain disease that is characterized by four major features... [2] Context 12: The cardinal signs of Perry syndrome are parkinsonism, neuropsychiatric symptoms, hypoventilation, and weight loss. [3] Context 13: Perry syndrome (the most common of the phenotypes associated with DCTN1) is characterized by parkinsonism, neuropsychiatric symptoms, hypoventilation, and weight loss. [4] Context 5: Depression; Suicidal thoughts; Apathy; and Social withdrawal. [5] Context 6: Perry syndrome is characterised by rapidly progressive parkinsonism often accompanied by depression/apathy, weight loss and central hypoventilation. [6] Context 9: It is characterized by parkinson-ism, psychiatric symptoms, unexpected weight loss, central hypoventilation, and transactive-response DNA-binding protein of...

Perry syndrome, also known as DCTN1-related parkinsonism, is a rare neurodegenerative disorder characterized by parkinsonism, depression/apathy, and other psychiatric symptoms.

Diagnostic Testing

The diagnosis of Perry syndrome is made through molecular genetic testing for the DCTN1 gene, which is the only gene currently associated with this condition [3]. This test is typically performed on individuals who exhibit clinical signs and symptoms of Perry syndrome, or those with a family history of the disease [6].

Key Diagnostic Features

The diagnostic criteria for Perry syndrome include:

• Parkinsonism: A pattern of movement abnormalities characterized by tremors, rigidity, bradykinesia (slow movement), and postural instability [5].
• Depression/Apathy: Patients often experience significant depressive symptoms or apathy.
• Other psychiatric symptoms: Mood swings, anxiety, and cognitive decline may also be present.

Imaging Studies

Brain imaging studies, such as MRI and dopamine transporter imaging, can help confirm the diagnosis of Perry syndrome. These tests may show:

• Mild cerebellar atrophy [7].
• Severely reduced radiotracer uptake in the striatum bilaterally, indicating significant dopaminergic dysfunction [7].

Challenges in Diagnosis

Early detection of Perry disease is still difficult, and most cases are initially misdiagnosed as Parkinson's disease (PD) or progressive supranuclear palsy (PSP) [8][9]. Accurate diagnosis requires a high index of suspicion and a thorough understanding of the clinical presentation.

References:

[3] - Diagnostic testing: The diagnosis of Perry syndrome is made by molecular genetic testing for DCTN1, the only gene known to be associated with this condition. [5] - Sep 1, 2015 — Perry syndrome is a progressive brain disease that is characterized by four major features: a pattern of movement abnormalities known as parkinsonism. [6] - This is a next generation sequencing (NGS) test appropriate for individuals with clinical signs and symptoms, suspicion of, or family history of Perry Syndrome. [7] - Brain MRI demonstrated only mild cerebellar atrophy. The dopamine transporter imaging showed severely reduced radiotracer uptake in striatum bilaterally. [8] - by Y Tsuboi · 2020 · Cited by 19 — Early detection of Perry disease is still difficult; in most cases, the patients are diagnosed with PD or progressive supranuclear palsy until ... [9] - by Y Tsuboi · 2021 · Cited by 19 — Perry syndrome (Perry disease) is a hereditary neurodegener- ative disease with an autosomal dominant inheritance, parkin- sonism, psychiatric symptoms, ...

Perry syndrome, also known as Perry disease, is a rare inherited neurodegenerative disorder that affects movement and cognitive functions. While there is no causal treatment for Perry syndrome, various drug therapies have been explored to manage its symptoms.

Levodopa Therapy High doses of levodopa, often above 1-2 grams per day, have been used to treat parkinsonism-like symptoms in patients with Perry syndrome [8]. This therapy can help alleviate tremors and other movement abnormalities associated with the disease. However, response to levodopa can be erratic or absent in some cases [1].

Diaphragmatic Pacemaker In severe cases of respiratory insufficiency, a diaphragmatic pacemaker may be considered as an option for treatment [8]. This device helps stimulate the diaphragm to breathe, improving respiratory function.

Experimental Therapies Researchers have been exploring disease-modifying therapies for Perry syndrome. For example, reducing TDP-43 protein levels has shown promise in improving neuronal activities in a Drosophila model of the disease [9].

It is essential to note that these treatments are not universally effective and may vary from person to person. Consultation with a healthcare professional is crucial for determining the best course of treatment for individuals with Perry syndrome.

References: [1] Z Gajda · 2024 [8] Aug 4, 2023 [9] by T Mishima · 2024

Perry syndrome, also known as Perry disease, is a rare hereditary neurodegenerative disorder that requires careful consideration in the differential diagnosis of parkinsonism.

Key Differential Diagnoses

• Other forms of familial early-onset parkinsonism, particularly those associated with mutations in the PARK2, PINK1, and PARK7 genes [1][4]
• Parkinson disease
• Progressive supranuclear palsy
• Frontotemporal dementia

These conditions can present with similar symptoms to Perry syndrome, such as parkinsonism, psychiatric symptoms, weight loss, central hypoventilation, and transactive-response DNA-binding protein (TDP-43) pathology [2][3].

Important Considerations

Perry syndrome should be considered in the differential diagnosis of Parkinsonism, particularly in autosomal dominant pedigrees [1][4]. Early diagnosis is crucial for providing appropriate management and support to affected individuals and their families.

Summary of Differential Diagnoses

In summary, the differential diagnoses for Perry syndrome include:

• Other forms of familial early-onset parkinsonism
• Parkinson disease
• Progressive supranuclear palsy
• Frontotemporal dementia

These conditions require careful consideration in the diagnostic process to ensure accurate diagnosis and management.

References: [1] BM Aji (2013) - Perry syndrome needs to be considered in the differential diagnosis of Parkinsonism, particularly in autosomal dominant pedigrees. [2] Y Tsuboi (2021) - It is characterized by parkinsonism, psychiatric symptoms, unexpected weight loss, central hypoventilation, and transactive-response DNA-binding protein (TDP-43) pathology. [3] Y Tsuboi (2020) - Perry syndrome (Perry disease) is a hereditary neurodegenerative disease with an autosomal dominant inheritance, parkinsonism, psychiatric symptoms, unexpected weight loss, central hypoventilation, and transactive-response DNA-binding protein (TDP-43) pathology. [4] BM Aji (2013) - Perry syndrome needs to be considered in the differential diagnosis of Parkinsonism, particularly in autosomal dominant pedigrees.