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

Selected Autosomal Recessive Chorea Syndromes

When the family history is incomplete or absent, autosomal recessive chorea syndromes should also be considered in patients with a Huntington's disease phenotype as some of these may produce similar phenotypes. In view of word limitations, only an incomplete selection will be discussed in the following.

Chorea-acanthocytosis and McLeod Syndrome

Both chorea-acanthocytosis (ChAc) and McLeod syndrome belong to the so-called core neuroacanthocytosis syndromes characterized by neurodegeneration of the basal ganglia and red cell acanthocytosis.[65]

ChAc is a rare autosomal recessive neurodegenerative disorder due to mutations in the VPS13A gene on chromosome 9 encoding chorein.[66,67] It is estimated that about 1000 ChAc cases exist worldwide.[68] ChAc causes movement disorders (including chorea, dystonia, parkinsonism and tics), cognitive impairment and psychiatric features with great similarities to Huntington's disease. However, clinical characteristics like dystonia with prominent orofacial involvement with tongue protrusion, involuntary tongue-biting and lip-biting and rubber-man-like appearance may indicate a diagnosis distinct from classic Huntington's disease.[69,70] Furthermore, seizures (which occur infrequently in late-onset Huntington's disease) are seen in half of patients, and myopathy and axonal neuropathy are common.[71] The disease usually starts in the twenties and progresses slowly over 15–30 years.[65]

Blood tests reveal elevated levels of creatine phosphokinase in most cases. The detection of acanthocytosis often remains elusive, although the probablity of detecting the characteristic deformed erythrocytes can be increased by using a 1 : 1 dilution with physiological saline and phase contrast microscopy.[72] Analysis of protein (chorein) levels is, therefore, recommended. Neuroradiological findings include progressive striatal atrophy with a maximum in the caudate head.[73,74] Postmortem examinations have shown a neuronal loss and gliosis predominantly affecting the caudate nucleus, putamen, globus pallidus, thalamus and substantia nigra. In comparison to Huntington's disease, no significant cortical disease nor specific neuropathological features such as inclusion bodies have been detected.[75,76]

McLeod syndrome is inherited in an X-linked matter and is caused by mutations in the XK gene encoding an antigen of the Kell blood group system.[77,78] Clinically, McLeod syndrome shares an extended phenotypic overlap with ChAc with an HDL phenotype, seizures, peripheral neuropathy and myopathy, and sometimes presence of tongue protrusion, feeding dystonia, lip-biting or tongue-biting and rubber-man-like appearance.[77,79] In contrast to ChAc, dystonia is less common, the age of onset is later and the disease duration may be more than 30 years.[77,80] Furthermore, cardiomyopathy and arrhythmia, which are seen in 60% of McLeod syndrome patients, are distinguishing features.[81]

Wilson Disease

Although Wilson disease most commonly presents with parkinsonism, dystonic features and cerebellar signs may occur. Chorea was described in 9% of Wilson patients and it should, therefore, be considered in a chorea patient with a negative HTT gene test.[82] Overall, it is recommended to perform copper studies in any young and adult patients with a new movement disorder.

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