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


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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.
 
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. Huntingtons can be diagnosed on MRI by caudate atrophy with appropriate history, and also by genetic testing.
 
Differential diagnosis includes hepatocerebral degeneration, schizophrenia with tardive dyskinesia, other chorea's,  and drug reactions.

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