Huntington disease

Claudia M Testa MD PhD (Dr. Testa of Virginia Commonwealth University received research grants from Auspex and Teva.)
Joseph Jankovic MD, editor. (Dr. Jankovic, Director of the Parkinson's Disease Center and Movement Disorders Clinic at Baylor College of Medicine, received research funding from Allergan, Allon, Ceregene, Chelsea, EMD Serono, Impax, Ipsen, Lundbeck, Medtronic, Merz, and Teva, and compensation for his services as a consultant or an advisory committee member by Allergan, Auspex, EMD Serono, Lundbeck, Merz, Neurocrine Biosciences, and Teva.)
Originally released February 22, 1994; last updated July 11, 2017; expires July 11, 2020

This article includes discussion of Huntington disease and Huntington chorea. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Huntington disease is an autosomal dominant neurodegenerative disorder characterized by motor, behavioral, and cognitive manifestations. It is caused by an expansion of a trinucleotide repeat in the gene encoding huntingtin (HTT) on chromosome 4. Although the onset of disease is currently defined by its motor manifestations, the presence of cognitive and behavioral symptoms prior to motor symptoms is increasingly recognized. A growing range of non-motor and motor symptoms combine to produce functional changes, important targets for symptomatic treatment and clinical trial outcomes. Thoughtful interdisciplinary symptomatic care can make a major positive impact for patients and families. The development of biomarkers in Huntington disease is an area of growing research and is particularly important for studies of disease-modifying therapy. With the help of biomarker outcomes, disease-modifying therapies are increasingly piloted in nonmanifest mutation carriers as well as early motor symptomatic individuals. Predictive (prior to symptoms) genetic testing protocols take a wide range of information on Huntington disease genetics, inheritance, symptoms, and progression into account. In this article, the author explores the advances and possible therapeutic targets in the treatment of this devastating disease.

Key points

 

• Cognitive and behavioral changes may occur years prior to the onset of definitive motor signs.

 

• Changes in sleep, weight loss, and autonomic dysfunction are now recognized as primary and treatable Huntington disease symptoms.

 

• Impacting functional outcomes and quality of life are increasingly important symptomatic care and clinical trial goals.

 

• Management of Huntington disease involves an interdisciplinary whole-family approach, utilizing expertise in neurology, psychiatry, neuropsychology, rehabilitation and wellness, and nutrition in addition to genetic and social issues.

 

• Presymptomatic and confirmatory genetic testing is best utilized with the support of genetic counseling as well as regional and international guidelines.

 

• Treatment of Huntington disease currently remains symptomatic, but potential new therapeutic targets are being actively explored in both manifest and nonmanifest populations.

Historical note and terminology

The clinical syndrome was delineated in the English literature in 1872 by George Huntington (Wexler et al 2016a), who reported:

Hereditary chorea. . .confined to certain and fortunately a few families, and has been transmitted to them, an heirloom from generations away back in the dim past. It is spoken of by those in whose veins the seeds of the disease are known to exist, with a kind of horror. . . There are three marked peculiarities in this disease: 1. Its hereditary nature. 2. A tendency to insanity and suicide. 3. Its manifesting itself as a grave disease only in adult life".

The degeneration of the striatum was recognized as the essential neuropathologic feature around the turn of the century (Anton 1896; Lanois and Paviot 1897; Alzheimer 1911). The genetic mutation causing Huntington disease, located in a novel gene on the short arm of chromosome 4, was the first human genetic variant to be localized by linkage analysis using restriction fragment length polymorphisms (Gusella et al 2014), and the first demonstration of an expansion of a trinucleotide repeat as a disease causing mutation type (Wexler et al 2016a). This discovery was the result of a decades-long effort by a multinational multidisciplinary research team together with thousands of interrelated volunteers living at risk for or affected by Huntington disease in the Lake Maracaibo area of Venezuela (Hereditary Disease Foundation website) (Wexler et al 2016a).

The content you are trying to view is available only to logged in, current MedLink Neurology subscribers.

If you are a subscriber, please log in.

If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.

If you have never registered before, click Learn More about MedLink Neurology  or view available Service Plans.