What are the clinical features of Huntington's disease?

Clinical Features of Huntington's Disease

Huntington's disease (HD) is a neurodegenerative disease of mid-life onset that produces choreic movements, cognitive decline, and psychiatric changes, with symptoms resulting from selective loss of neurons, most notably in the caudate nucleus and putamen. 1

Core Clinical Manifestations

Motor Symptoms

• Choreic movements are the classic sign of HD, characterized by involuntary, irregular, purposeless, non-rhythmic, abrupt, rapid, jerky movements that flow from one body part to another 1
• Juvenile-onset HD (approximately 5% of cases) presents with rigidity, spasticity, and intellectual decline before age 20 years 1
• Motor symptoms progressively worsen over the disease course of 15-20 years, eventually affecting all muscle groups 1

Cognitive Symptoms

• Progressive cognitive decline affecting executive function, attention, processing speed, and visuospatial abilities 1
• Dementia develops as the disease progresses, with significant impact on problem-solving abilities and independent living 2
• Cognitive impairment significantly predicts functional decline in HD patients 2

Psychiatric/Behavioral Symptoms

• Psychiatric changes including depression, anxiety, irritability, apathy, and personality changes 1
• Behavioral disturbances that may require both pharmacological and non-pharmacological management 3
• Psychiatric symptoms often precede motor symptoms and contribute substantially to disease morbidity 4

Disease Progression and Prognosis

• HD typically progresses over 15-20 years after symptom onset 1
• Complete dependency in daily activities develops in advanced stages 5
• Most common causes of death are aspiration pneumonia and suicide 1, 5

Genetic Basis and Inheritance

• Autosomal dominant inheritance pattern with complete penetrance when CAG repeat numbers are ≥40 1
• Variable penetrance for alleles carrying 36-39 CAG repeats 1
• Inverse relationship between CAG repeat length and age of onset - longer repeats correlate with earlier onset and increased disease severity 1
• Juvenile HD typically associated with >55 CAG repeats 1

Clinical Variants

• Adult-onset (typical) HD: onset between 30-50 years with predominant chorea 1
• Juvenile-onset HD: onset before age 20 with predominant rigidity and rapid progression 1
• Late-onset HD: milder symptoms appearing after age 60 5

Diagnostic Considerations

• Diagnosis based on clinical symptoms in individuals with family history and confirmed by DNA testing 1
• Genetic testing reveals CAG repeat expansion (≥36 repeats) in the HTT gene on chromosome 4p16.3 1
• Predictive testing should only be performed in asymptomatic at-risk adults after appropriate genetic counseling 1

Management Approach

• No curative treatment currently available 1
• Symptomatic treatment of chorea with deutetrabenazine, valbenazine, or antipsychotics 6
• Psychiatric symptoms often respond well to appropriate pharmacological intervention 4
• Non-pharmacological approaches include establishing predictable routines, creating safe environments, and breaking complex tasks into simple steps 3

Common Pitfalls in Clinical Assessment

• Overlooking psychiatric symptoms which may precede motor manifestations 6, 3
• Failing to recognize cognitive decline that significantly impacts functionality 2
• Neglecting the impact of HD on family members who may be at risk or serving as caregivers 4
• Initiating pharmacological treatment without first considering non-pharmacological approaches 3