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

An Overview

Felix Gövert and Susanne A. Schneider


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

In This Article

Benign Hereditary Chorea

Benign hereditary chorea (BHC) is a rare autosomal dominant disease, which is characterized by nonprogressive chorea with early onset in childhood and absence of dementia and caudate atrophy. Several mutations in the associated thyroid transcription factor-1 (TITF1 gene (NKX2-1), located on chromosome 14, have been described. The encoded thyroid transcription factor 1 is essential for the organogenesis of the lungs, thyroid and basal ganglia.[56,57]

The typical clinical phenotype is infancy-onset chorea preceded by hypotonia. Other movement disorders like myoclonus, dystonia, tics, tremor and ataxia may be associated. Chorea tends to improve in early adulthood and then remains stable over time, but there is clinical heterogeneity within and between families. Notably, mental retardation is reported in 15% of cases and learning difficulties are quite frequent. Because of the mentioned role of NKX2-1, respiratory and thyroid disorders are also frequently seen (36–49%) and may be a useful hint towards the diagnosis.[58] Neuroimaging is usually normal apart from reduced uptake in basal ganglia and the thalamus in brain single photon emission computed tomography.[59] Pathological studies also reveal no significant abnormalities using standard methods. Immunohistochemical staining showed loss of most TITF-1-mediated striatal interneurons in BHC brains.[60,61] Levodopa, haloperidol, chlorpromazine, tetrabenazine and prednisone showed favourable effects as a symptomatic treatment for BHC.[58,62,63]

Genetic heterogenetiy of BHC has been suggested when Shimohata et al.[64] reported two Japanese families with adult-onset slowly progressive chorea without dementia inherited in an autosomal dominant pattern in whom Huntington's disease, basal ganglia calcification and other HDL syndromes were excluded by genetic testing. MRI imaging revealed no abnormalities. Genetic work-up showed linkage to chromosome 8q21.3–q23.3. Because of the clinical resemblance with BHC the disease was named benign hereditary chorea type 2.