Huntington's Disease and Huntington's Disease-like Syndromes

An Overview

Felix Gövert and Susanne A. Schneider

Disclosures

Curr Opin Neurol. 2013;26(4):420-427. 

In This Article

Huntington's Disease

The motor phenotype in Huntington's disease is mainly characterized by chorea, but also dystonia and parkinsonism with onset in midlife. Patients demonstrate abnormal facial expression and impaired saccadic eye movements. With progressing disease, there is increasing postural instability and dysarthria as well as difficulties with chewing and swallowing. Early in the course, personality changes or psychiatric disease (depression and anxiety) develop, often preceding the motor onset. Estimated rates for lifetime prevalence of psychiatric disorders range between approximately 30–75%. Cognitive abilities are also progressively impaired, especially affecting executive functions (abstract thinking, planning and inhibition of inappropriate behaviour) and, later, memory function.

In successive generations onset tends to develop earlier in life (correlating with longer repeat sizes; so-called genetic anticipation), particularly when inherited from the father. The phenotype in such early-onset cases may differ from classic Huntington's disease and may be predominated by parkinsonism (Westphal variant). Studies show that about 6–10% of Huntington's disease cases start before the age of 20 years with an akinetic–rigid syndrome.

Huntington's disease is inherited in an autosomal dominant fashion. Interestingly, homozygous patients have also rarely been described.[1] Recent studies aim at predicting symptom onset and understanding earliest (including presymptomatic) disease stages in order to define therapeutic windows when potential therapy may be beneficial. Thus, in large consortia (such as TRACK-HD and PREDICT-HD[2,3]) individuals at risk (genetically confirmed carriers) are being followed longitudinally to detect subtle changes on neuroimaging, cognitive function tests and other parameters.

The pathophysiology of Huntington's disease is not fully understood. The mutant huntingtin protein (Htt) is large and ubiquitously expressed, with damaging effects on neurons. Animal models recapitulate the molecular, cellular and clinical phenotypes and have shed light on the pathopysiological underpinnings, allowing the search for mechanistic treatments.[4] However, so far treatment remains symptomatic, ideally in a multidisciplinary setting.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....