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

Abstract and Introduction

Abstract

Purpose of review The differential diagnosis of chorea syndromes may be complex and includes various genetic disorders such as Huntington's disease and mimicking disorders called Huntington's disease-like (HDL) phenotypes. To familiarize clinicians with these (in some cases very rare) conditions we will summarize the main characteristics.

Recent findings HDL disorders are rare and account for about 1% of cases presenting with a Huntington's disease phenotype. They share overlapping clinical features, so making the diagnosis purely on clinical grounds may be challenging, however presence of certain characteristics may be a clue (e.g. prominent orofacial involvement in neuroferritinopathy etc.), Information of ethnic descent will also guide genetic work-up [HDL2 in Black Africans; dentatorubral-pallidoluysian atrophy (DRPLA) in Japanese etc.], Huntington's disease, the classical HDL disorders (except HDL3) and DRPLA are repeat disorders with anticipation effect and age-dependent phenotype in some, but genetic underpinnings may be more complicated in the other chorea syndromes.

Summary With advances in genetics more and more rare diseases are disentangled, allowing molecular diagnoses in a growing number of choreic patients. Hopefully, with better understanding of their pathophysiology we are moving towards mechanistic therapies.

Introduction

Chorea is a hyperkinetic movement disorder characterized by excessive spontaneous, involuntary movements which occur abruptly, and are irregularly timed and random in their distribution. Severity may range from mild focal involvement (e.g. of the hands) to a severe generalized involvement with violent choreiform movements of the limbs and trunk. Chorea may in some instances be restricted to one side of the body (hemichorea).

Chorea may have numerous causes including acquired and inherited causes. The most important inherited cause of chorea is Huntington's disease, a slowly progressive autosomal dominant neurodegenerative disease characterised by impaired motor function (in particular chorea, but also dystonia and parkinsonism), cognitive impairment and psychiatric symptoms. Since the identification of the gene underlying Huntington's disease, huntingtin (HTT), in 1993, much progress has been made with regards to understanding the underlying pathophysiology. Furthermore, it has become clear that not all patients who present with a phenotype typical for Huntington's disease actually have Huntington's disease but rather may have an alternative diagnosis. For these related but distinct disorders, the term Huntington's disease-like (HDL) disorders was coined.

Recent developments in the field of both Huntington's disease and HDL disorders prompted us to review these conditions. We will summarize the main clinical features, pathophysiological and genetic underpinnings and other key characteristics.

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