What are the presenting symptoms of Huntington’s disease?

Presenting Symptoms of Huntington's Disease

The presenting symptoms of Huntington's disease typically include a triad of motor disturbances (particularly chorea), cognitive decline, and psychiatric manifestations, with motor symptoms often being the most noticeable initial presentation.

Motor Symptoms

• Chorea: Involuntary, irregular, purposeless, non-rhythmic, abrupt movements that flow from one body part to another 1
• Motor impersistence: Inability to maintain a sustained motor contraction
• Impaired voluntary movements: Bradykinesia, hypokinesia, and rigidity
• Gait disturbances: Unsteady, wide-based gait with poor balance
• Postural instability: Increased risk of falls
• Dysarthria: Slurred speech that becomes progressively worse
• Dysphagia: Difficulty swallowing that worsens over time

Cognitive Symptoms

• Executive dysfunction: Difficulty with planning, organizing, prioritizing, and multitasking
• Impaired attention and concentration
• Slowed processing speed: Taking longer to process information and respond
• Memory deficits: Particularly affecting retrieval rather than storage
• Visuospatial difficulties: Problems with spatial awareness and perception
• Poor judgment and decision-making
• Difficulty with new learning

Psychiatric Symptoms

• Depression: Often one of the earliest psychiatric manifestations
• Anxiety: Frequently co-occurs with depression
• Irritability and aggression: Can be particularly challenging for caregivers
• Apathy: Progressive loss of motivation and initiative
• Obsessive-compulsive behaviors: Repetitive thoughts and actions
• Psychosis: Delusions and hallucinations in some cases
• Personality changes: Including disinhibition and emotional lability

Systemic Symptoms

• Weight loss: Often progressive despite adequate caloric intake
• Sleep disturbances: Insomnia and disrupted sleep-wake cycles
• Autonomic dysfunction: Including sweating abnormalities
• Cardiovascular, respiratory, gastrointestinal, and urinary symptoms may also occur as the disease progresses 2

Temporal Progression

The onset of Huntington's disease is typically insidious, with symptoms gradually worsening over time. The average age of onset is 30-50 years, but juvenile forms (onset before age 20) and late-onset forms also occur 3.

Prodromal Phase

• Subtle cognitive changes
• Mild psychiatric symptoms
• Minor motor abnormalities that may go unnoticed
• Can begin up to 15 years before formal diagnosis 4

Early Disease

• Chorea becomes more noticeable
• Cognitive difficulties begin to affect daily functioning
• Psychiatric symptoms often become more prominent

Advanced Disease

• Severe motor impairment with rigidity often replacing chorea
• Profound cognitive decline
• Significant functional dependence

Diagnostic Considerations

The diagnosis of Huntington's disease is confirmed through genetic testing showing an expanded CAG trinucleotide repeat (>36 repeats) in the huntingtin gene on chromosome 4 5. However, recognition of the characteristic clinical presentation is crucial for prompting appropriate genetic testing.

Key Points for Clinicians

• Early symptoms may be subtle and attributed to other conditions
• Family history is crucial - approximately 90% of cases have a known family history
• The CAG repeat length correlates inversely with age of onset (longer repeats = earlier onset)
• Juvenile-onset HD (Westphal variant) often presents with rigidity rather than chorea
• Consider HD in any patient with unexplained movement disorders, cognitive decline, or psychiatric symptoms, especially with a positive family history

Understanding the full spectrum of presenting symptoms is essential for early diagnosis, appropriate management, and genetic counseling for at-risk family members.