Huntington's Disease

Huntington's disease (HD) is a rare inherited neurological disorder that causes progressive degeneration of nerve cells in the brain. HD affects various aspects of a person's functional abilities, such as movement, cognition, and behavior. It is caused by a mutation in the huntingtin gene, which produces a toxic protein that accumulates and damages different regions of the brain. HD is usually diagnosed in middle age, but it can also occur in children or older adults. There is no cure for HD, and its symptoms worsen over time, leading to disability and death. HD is a complex and challenging disease that requires multidisciplinary care and management.

Fig.1 Pathogenetic cellular mechanisms in Huntington’s disease. (McColgan P, 2018)

Clinical Manifestations

Huntington's disease (HD) affects various aspects of a person's functional abilities, such as movement, cognition, and behavior. The clinical manifestations of HD can be divided into three main categories: movement disorders, cognitive disorders, and psychiatric disorders. These symptoms can vary greatly from person to person and can change throughout the course of the disease.

Movement disorders are the most characteristic feature of HD. They include involuntary jerking or writhing movements (chorea), muscle problems such as rigidity or muscle contractures (dystonia), slow or unusual eye movements, impaired gait, posture, and balance, difficulty with speech or swallowing, and impairments in voluntary movements. Chorea is usually the first symptom to appear and can affect any part of the body. It can interfere with daily activities, such as eating, dressing, writing, or driving. Dystonia can cause abnormal postures or spasms of the limbs, trunk, or face. Eye movements can be slow, erratic, or limited in range. Gait and balance problems can increase the risk of falls and injuries. Speech and swallowing difficulties can lead to communication problems and malnutrition. Impairments in voluntary movements can affect the ability to work, perform daily tasks, communicate, and remain independent.

Clinical Diagnosis and Treatment Methods

Huntington's disease (HD) is diagnosed based on the presence of characteristic clinical features, a positive family history of HD, and a genetic test that confirms the expansion of the CAG repeat in the huntingtin gene. The genetic test is the most definitive and accurate way to diagnose HD, but it is not mandatory and requires informed consent and genetic counseling. The genetic test can also be used for predictive testing in asymptomatic individuals who are at risk of inheriting HD, but this decision involves ethical, psychological, and social implications. Additionally, the genetic test can be used for prenatal testing or preimplantation genetic diagnosis in couples who wish to have children without HD.

There is no cure for HD, and no treatment can stop or reverse the progression of the disease. Current treatment options aim to improve the quality of life for patients and their caregivers, reduce symptom severity, delay the onset of complications, and provide palliative care. The treatment of HD requires a multidisciplinary approach involving neurologists, psychiatrists, psychologists, nurses, physiotherapists, occupational therapists, speech therapists, nutritionists, social workers, and genetic counselors. Treatment modalities include pharmacological therapy, non-pharmacological therapy, and gene therapy.

Conclusion

Huntington's disease (HD) is a rare inherited neurological disorder that causes progressive degeneration of nerve cells in the brain, affecting movement, cognition, and behavior. HD is caused by a mutation in the huntingtin gene and is diagnosed through clinical features, family history, and genetic testing. There is no cure for HD, and it leads to disability and death. HD necessitates multidisciplinary care and management. Current treatments aim to improve the quality of life, reduce symptom severity, delay complications, and provide palliative care. However, these treatments are only symptomatic and do not alter the disease course. There is a pressing need for more effective and disease-modifying therapies for HD. Recent research has offered new insights and potential targets for HD. Researchers are developing and testing novel drugs, gene therapies, and stem cell therapies. Preventing HD is crucial for reducing the disease burden. Prevention strategies encompass genetic counseling, prenatal testing, preimplantation genetic diagnosis, and lifestyle modifications. Psychological support can aid individuals in coping with the challenges of living with HD or being at risk of developing it.

References

1. Walker FO. Huntington's disease. Lancet. 2007 Jan 20;369(9557):218-281
2. McColgan P, Tabrizi SJ. Huntington's disease: a clinical review. Eur J Neurol. 2018 Jan;25(1):24-34.
3. Phillips W, et al. The current clinical management of Huntington’s disease. Mov Disord. 2008 Aug 15;23(11):1491-5042
4. Bonelli RM, et al. A systematic review of the treatment studies in Huntington’s disease since 1990. Expert Opin Pharmacother. 2007 Feb;8(2):141-533
5. Novak MJ, et al. Huntington’s disease. BMJ. 2010 Jun 30;340:c3109.
6. Fasano A, et al. Tetrabenazine. Expert Opin Pharmacother. 2009 Dec;10(17):2883-96.
7. Quinn L, et al. Clinical recommendations to guide physical therapy practice for Huntington disease. Neurology. 2020 Feb 4;94(5):217-28.
8. Bonelli RM, et al. Pharmacological management of Huntington’s disease: an evidence-based review. Curr Pharm Des. 2006;12(21):2701-20.
9. McGarry A, et al. A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease. Neurology. 2017 Jan 10;88(2):152-159.