- HD gene chr. 4p16.3, expansion of CAG trinucleotide repeat. Protein= huntingtin, mutation= expansion of polyglutamine segment. Norma repeat is <26 repeats, Hungtingtons disease if = or >36 repeats
- Genetic testing for CAG repeat expansion in the huntingin gene
Chorea, personality change, dementia
Chorea: initially as fidgety movements, then it affects fingers, arms, legs, face, trunk
Westphal variant: onset before 20 y.o. Presents with bradykinesia, rigidity, dystonia, epileptic seizures
Features on Investigations:
MRI: atrophy of the caudate nucleus, bilateral striatum hyperintensity in juvenile Huntington disease
Gross: Atrophy of caudate nucleus (flattened or concave), also some atrophy of parietal & occipital lobes. At end stage; atrophy of globus pallidus, thalamus, brain stem & cerebellum.
- Neuronal loss, astrocytosis affecting the caudate nucleus, putamen & nucleus accumbens. Neuronal loss in cerebral cortex & mesial temporal structures. In the juvenile form it also affects the cerebellum with loss of Purkinje & granular cell layers.
- Immunohistochemistry: huntingtin positive intraneuronal inclusions & neurites, ubiquitin positive intraneuronal inclusions & neurites. These occur in the neostriatum, cortex & hippocampus.
- Tetrabenazine. [RCT]
- Or Haloperidol or chlorpromazine
- or reserpine
Approach to cognitive impairment,
- Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology, 2006. 66(3): p. 366-72.