Huntington's Chorea (Huntington's Disease, HD)

Timothy C. Hain, MD Page last modified: January 5, 2008

Huntington's chorea is a dominantly inherited disease typified by choreoathetosis, rigidity, dementia, ataxia, and ophthalmoplegia.It was first described by George Huntington in 1872. Incidence is 5-10/100,000. Genetically, it is an autosomal dominant disorder with complete penetrance. The mutation, CAG-trinucleotide repeats, may expand in descendent generations explaining anticipation. A similar syndrome has been reported in SCA-17, another CAG repeat disease (Toyoshima et al, 2004).

Onset occurs from childhood (10% of cases) into late life, but is usually in the mid-30s to mid-40’s. Progression is relentless usually ending in death within 10-20 years. The CAG repeats encode glutamines in the gene for "huntington". However the contribution of the mutant form of huntington is presently unclear. Gene imprinting explains the transmission of the childhood form primarily through the father. The disease often presents as "nervousness", and depression. Eventually progresses to include dementia and slowed eye movements. In juvenile HD, rigidity and parkinsonian tremor may be the primary manifestation.

HD is a basal ganglia disease; the portions most severely affected are caudate and putamen. The most significant neuropathological change is a preferential loss of medium spiny neurons in the neostriatum. Biochemically there is marked loss of GABA, substance P, enkephalin, angiotension converting enzyme. Neuronal changes begin very early in life, perhaps even from birth. There is no known treatment that will stop progression, but there are symptomatic treatments such as haloperidol.

Diagnosis:

Prolonged latency of saccades in a patient with mild Huntington's chorea. Blue-target, Red-horizontal. Dashed lines are 1 second apart.

 

 

 

 

 

 

 

 

 

Huntingtons can be diagnosed on MRI by caudate atrophy with appropriate history, and also by genetic testing. On ENG testing, patients may show slow saccades and/or prolonged latency of saccades.

Differential diagnosis includes hepatocerebral degeneration (Wilson's disease), schizophrenia with tardive dyskinesia, other chorea's such as SCA-17,  and drug reactions.

Treatment:

Treatment is presently symptomatic. Recent animal work (Duan et al, 2004) suggests that SSRI type antidepressants may be worth considering.

References:

• Duan W and others. Paroxetine retards disease onset and progression in huntingtin mutant mice. Ann Neurol 2004:55:590-94
• Penny JB and Young AB, Huntington’s Disease IN Parkinson’s Disease and Movement Disorders (eds. Jankovic and Tolosa), 1993, Williams & Wilkins).
• Sapp et al. Huntingtin localization in brains of normal and huntington's disease patients. Ann Neurol 1997:42:604-12
• Toyoshima et al. SCA17 homozygote showing huntington's disease-like phenotype. Ann Neurol 2004:55:281-286