Cognitive Decline and Other Late-Stage Neurologic Complications in Cockayne Syndrome

Area of Science:

• Neuroscience
• Genetics
• Rare Diseases

Background:

• Cockayne syndrome (CS) is a rare genetic disorder causing premature aging and severe neurodegeneration.
• Clinical features of neurodegeneration in adult CS patients remain poorly understood.

Purpose of the Study:

• To characterize the clinical features of neurodegeneration in adult patients with Cockayne syndrome.
• To investigate the frequency and types of neurological complications in individuals with CS surviving beyond 18 years.

Main Methods:

• Retrospective observational study across three international centers.
• Analysis of medical records for neurological complications including cognitive decline, tremors, neuropathy, seizures, and strokes.
• Review of neuroimaging data (MRI) for cerebral atrophy and white matter changes.

Main Results:

• Nearly all adult CS patients (94.4%) exhibited neurocognitive/neuropsychiatric decline.
• Tremors and peripheral neuropathy were common; seizures and strokes were less frequent.
• Gait ataxia was universal, and MRI revealed cerebral atrophy (85.7%) and white matter changes (78.6%).

Conclusions:

• Neurocognitive/neuropsychiatric decline is a near-universal feature in adult CS patients.
• Impaired genome maintenance may underlie neurocognitive decline in CS and other neurodegenerative diseases.
• DNA damage response pathways represent potential therapeutic targets for CS-related neurological symptoms.