About Huntington’s disease

Today, we know more about Huntington's disease than ever before

Huntington's disease (HD) is a rare, monogenic neurodegenerative disease characterised by a triad of cognitive, behavioural and motor symptoms leading to functional decline and progressive loss of independence.5-8 It typically strikes in the prime of life, between 30 and 50 years of age,7 and impacts families across generations, with each child of a parent with HD having a 50/50 chance of developing the disease.5 There is currently no proven approach to slowing or stopping the relentless progression of this ultimately fatal disease.6

The more we learn about the mutant huntingtin (mHTT) protein responsible for causing HD, and how we may be able to lower its levels, the closer we get to unlocking the mysteries of this condition.

HD average prevalance rate

HD is the most common monogenic neurological disorder in the developed world. HD has an average prevalence rate of ~10 in 100,000, which has increased worldwide between 9–20% each decade.9-13

Watch to learn more about HD

HD is characterised by a triad of cognitive, behavioural and motor symptoms

HD leads to functional decline and loss of independence,7,8 and results in death on average 15 years after the onset of motor symptoms.14

Cognitive disturbances in HD can occur years before diagnosis and onset of motor symptoms, and deteriorate steadily as the disease progresses. Behavioural manifestations in HD are particularly diverse and can also occur many years before a clinical diagnosis of HD is made.15-18 Motor symptoms in HD are initially subtle and progress in a non-linear trajectory over the course of the disease.8,19

Cognitive* Language difficulties, decreased attention, difficulty retrieving information, deficits in learning and memory, emotional recognition problems, lack of awareness, reduced mental flexibility, cognitive slowing, and problems with planning.5–8 [5/Ghosh R & Tabrizi SJ. 2018; 6/Bates GP et al. 2015; 7/Roos RA. 2010; 8/Ross C et al. 2014]  Behavioural*  Apathy, depression, impaired judgment, irritability, sleep problems, impulsivity, suicidality, aggression and psychosis.5,7,8,20 [5/Ghosh R & Tabrizi SJ. 2018; 7/Roos RA. 2010; 8/Ross C et al. 2014; 20/Anderson KE et al. 2018]  Motor*  Chorea, bradykinesia, impaired speech, impaired walking, dystonia, akinesia, rigidity, decreased saccades, dysphagia, poor balance/risk of falls and tics.5,7,8 [5/Ghosh R & Tabrizi SJ. 2018; 7/Roos RA. 2010; 8/Ross C et al. 2014]

Since individuals experience these symptoms in their own unique way, HD can often be difficult to diagnose. This means it can also be challenging for patient care and a multidisciplinary approach may help improve disease management.

*This is not a comprehensive list of HD symptoms. Symptoms and signs differ for each individual with HD.7

HD is a continuum which can be described in three stages

Clinical diagnosis of HD is typically defined by the onset of unequivocal motor symptoms and occurs when people are in the prime of life, typically between the ages of 30 and 50 years.7,8,21,22 HD phasing terminology continues to evolve; however, the disease generally progresses through the presymptomatic, prodromal and manifest stages.5,7,22

The presymptomatic, prodromal, and manifest stages of HD

1. Presymptomatic

Individuals who carry the HD-causing gene mutation but have not yet developed any symptoms.5,6,8

2. Prodromal

Individuals experience subtle changes in cognition, mood and behaviour that appear years before diagnosis or onset of unequivocal motor signs.6,8,21,23 Brain changes, including striatal atrophy, are apparent.6

3. Manifest

Individuals with HD have unequivocal motor symptoms and are clinically diagnosed with HD.6,8

 

The significance of expanded cytosine–adenine–guanine repeats

Researchers identified that the number of cytosine–adenine–guanine (CAG) trinucleotide repeat expansions in the huntingtin gene (HTT) has been shown to correlate with the age of disease onset.4,5 It is known that a CAG repeat length of ≥40 results in definite HD,6,7,24-26 CAG repeat length inversely correlates with age of onset,5-7 and other genetic and environmental factors may also affect disease progression.5,8

The number of CAG repeats is key to pathogenesis24,25,27

The risk of HD can be defined by the number of CAG repeats that an individual has

A blood test can be performed to determine the CAG repeat length.4,27 More information can be found on the NIH website.

References

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