Huntington Disease

Diseases, ,

Genetics:

Autosomal dominant

  • 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

Clinical:

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

Pathology:

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.
Microscopic:

  • 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.

Treatment:

Chorea:

  • Tetrabenazine. [RCT]
  • Or Haloperidol or chlorpromazine
  • or reserpine

Related articles:

Approach to cognitive impairment,

References:

  1. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology, 2006. 66(3): p. 366-72.