Huntington’s Chorea: A Genetic Time Bomb

The Lancet, 2007

Search strategy and selection criteria I searched Pub Med from 1965-2005 for the term "Huntington's Disease" cross referenced with the terms "apoptosis", "axonal transport", "mitochondria", "animal model", "proteosome", "transcription", "juvenile", "suicide", "neurotransmitters", "age of onset", "identical twins", "neurodegeneration", and "imaging". I translated all non-English language publications that resulted from this search strategy. I mainly selected articles from the past fi ve years, but did not exclude commonly referenced and highly regarded older publications. I also searched the reference lists of articles identifi ed by this search strategy and selected those that I judged relevant. Several review articles and book chapters were included because they provide comprehensive overviews beyond the scope of this Seminar. The reference list was further modifi ed during the peer-review process based on comments from the reviewers. Year Event Publications (n)* 1374 Epidemic dancing mania described .. 1500 Paracelsus suggests CNS origin for chorea .. 1686 Thomas Sydenham describes post-infectious chorea .. 1832 John Elliotson identifi es inherited form of chorea 1 .. 1872 George Huntington characterises Huntington's disease 5 ..

2011

Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Prevalence in the Caucasian population is estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington's disease; JHD). The classic sign is chorea that gradually spreads to all muscles. All psychomotor processes become severely retarded. Patients experience psychiatric symptoms and cognitive decline. HD is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more) on the short arm of chromosome 4p16.3 in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination. Pre-manifest diagnosis should only be performed by multidisciplinary teams in healthy at-risk adult individuals who want to know whether they carry the mutation or not. Differential diagnoses include other causes of chorea including general internal disorders or iatrogenic disorders. Phenocopies (clinically diagnosed cases of HD without the genetic mutation) are observed. Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered in several countries. There is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blocking or depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which results in patients requiring fulltime care, and finally death. The most common cause of death is pneumonia, followed by suicide.

2016

European Journal of Public Health Studies

Huntington's disease (HD) is an incurable lethal inherited neurological disorder of brain cells caused by increased CAG repeats in the huntingtin gene. It is the disease of mind and body which causes uncontrolled movements, loss of intellectual faculties, and emotional disturbance leading to eventual death. HD is incurable, but treatment is available for the symptoms of this disease. Latest technologies and techniques are used to diagnose HD. Neuroimaging and genetic testing are two important diagnoses techniques are available to measure the progress of the disease at any later stage. Drastic research is underway to control the disease with neuro-transplantation and neuro-surgery as a potential treatment in future to cure HD. The advancements in science and technologies and research on HD have indicated bright chances of cure. In the future, this disease seems to become curable Huntington's disease. Article visualizations:

BMJ, 1983

The relative fertility of sons and daughters of patients with Huntington's chorea was found to be a little under 0 5 if they had been told of their risk of transmitting the disease before they had started their families. The effect was much the same in those who had attended the genetic clinic at The Hospital for Sick Children on a single occasion and those who had been told of their risk directly, or indirectly through the patient's spouse or family doctor, by the neurologist who was looking after their affected parent at the National Hospital for Nervous Diseases. If all offspring of patients were informed of their risk the effect on the prevalence of the disorder would be substantial, especially if the mutation rate is low and the reproductive fitness of patients in the past has been close to 10. Men and women at risk of developing the disease should not be seen on just one occasion, however: they need continued support by being seen regularly at a special neurological genetic clinic.

International Journal of Pharmacy and Pharmaceutical Sciences, 2021

Huntington's disease is a neurodegenerative disease which is caused by dominantly inherited cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin gene of chromosome 4. Present survey reveals 2.7 per 100000 people are affected by huntington's disease worldwide. The symptoms present with these patients are progressive motor, cognitive and psychiatric disorders. The early symptoms are chorea and loss of balance. This review aims to observe the present data available concerning huntington's disease, symptoms, age of onset, risk factors, benefits of early diagnosis and genetic attribution. There is no cure for the disease. The article searched, selected and reviewed were from google scholar, medscape, NIH MedlinePlus, PubMed database using MeSH terms huntington's disease, recent therapeutic advancement from 2003 to July 2021 with no language restriction and additional studies were included from the reference lists of relevant articles. The present review provides clinical features, diagnosis, symptomatic management and ongoing research. Hence this review will have an impact to create awareness for the society and researchers to find future treatment for Huntington's disease.

International Journal of Research in Pharmaceutical Sciences, 2020

Huntington’s disease (HD) is a rare autosomal dominant, fatal neurodegenerative disorder of the central nervous system characterized by unwanted choreaticmovements, behavioural disruption, psychiatric disturbances anddementia. This condition is characterized by progressive degeneration of neurons within the basal ganglia, primarily the caudate and the putamen. As the disease progresses, neuronal losses occur in the white matter, cerebral cortex and thalamus. In this article, the authors reviewed the genetic aspects, etiological factors, stages of the disease condition along with the signs and symptoms, various diagnostic procedures besides with the pharmacological and non-pharmacological management of the Huntington’s disease. This disease is inherited within the families, and the pathophysiology of Huntington disease is restricted to the brain, where degeneration begins initially in the striatum, spreads to the cortex and eventually appears throughout the brain.The pathogenesis of ...

American journal of human genetics, 1996

To those of us who began life when humans had 48 chromosomes and who began working in genetics when the (by then 46) chromosomes had no bands and chromosome 4 could not reliably be distinguished from chromosome 5, the mere ability to diagnose and correlate the clinical phenotypes of genetic disorders with their molecular genotypes is a source of continuing astonishment and pleasure. Indeed, molecular genetic analysis of neurogenetic disorders such as Huntington disease (HD) has provided a steady stream of challenges and surprises to all who believe the genetic principles that they were taught about these disorders. The paper by Rubinsztein et al. in this issue of the journal highlights yet another surprise, which was adumbrated even in the initial paper announcing the discovery of the HD gene: incomplete penetrance of HD gene mutations.

International Journal of Pharmacy and Pharmaceutical Sciences

Huntington’s disease is a neurodegenerative disease which is caused by dominantly inherited cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin gene of chromosome 4. Present survey reveals 2.7 per 100000 people are affected by huntington’s disease worldwide. The symptoms present with these patients are progressive motor, cognitive and psychiatric disorders. The early symptoms are chorea and loss of balance. This review aims to observe the present data available concerning huntington’s disease, symptoms, age of onset, risk factors, benefits of early diagnosis and genetic attribution. There is no cure for the disease. The article searched, selected and reviewed were from google scholar, medscape, NIH MedlinePlus, PubMed database using MeSH terms huntington’s disease, recent therapeutic advancement from 2003 to July 2021 with no language restriction and additional studies were included from the reference lists of relevant articles. The present review provides clin...