DCTN1-related Parkinson-plus disorder (Perry syndrome)

Area of Science:

• Neurogenetics
• Neurology
• Molecular Biology

Background:

• Perry syndrome, a DCTN1-related Parkinson-plus disorder, is an autosomal dominant neurodegenerative condition.
• It is characterized by parkinsonism, weight loss, mood changes, and central hypoventilation, with respiratory insufficiency being the primary cause of mortality.
• This rare disorder, a distinct TDP-43 proteinopathy, affects individuals globally and poses diagnostic challenges due to clinical overlap with other neurodegenerative diseases.

Observation:

• The case highlights the diagnostic difficulties in recognizing DCTN1-related Parkinson-plus disorder.
• Genetic confirmation of the DCTN1 mutation was obtained only after the patient's death.
• This underscores the potential for delayed or incorrect diagnoses in rare neurodegenerative conditions.

Findings:

• DCTN1 mutations are confirmed as the cause of this specific TDP-43 proteinopathy.
• The rarity and overlapping symptoms of Perry syndrome contribute to diagnostic delays.
• Early recognition and intervention, particularly ventilatory support, can potentially improve life expectancy.

Implications:

• Prompt genetic diagnosis is critical for effective management and improved outcomes in Perry syndrome.
• Increased awareness and understanding of DCTN1-related disorders are necessary for earlier detection.
• Despite potential for improved life expectancy with ventilatory support, the overall prognosis remains poor without timely diagnosis.