Case Study presented by Jacob Klapper and Matthew Snyder, page3

Diagnosis and Discussion

The presented case describes onset of Huntington’s Disease before the third decade of life. Such juvenile-onset cases of HD are differentiated from classic adult-onset HD cases by a number of clinical, pathological and genetic features. Juvenile HD patients typically do not present with chorea, but instead with rigidity or seizures. With progression of disease, classic uncontrolled, choreoathetotic movements do develop. Behavioral, cognitive or psychiatric difficulties are prominent, as seen in this patient, who presented with a decline in school performance and is currently being treated for psychosis. Although degeneration and atrophy in the caudate and putamen are seen in juvenile HD patients as in adult-onset HD patients, a more widespread pattern of neurodegeneration is usually seen both radiologically and neuropathologically. Neuronal loss in the Purkinje and granule cells of the cerebellum is common, as is atrophy of the dentate nucleus, globus pallidus, hippocampus and neocortex.

An interesting genetic feature of HD is anticipation, which may be defined as worsening disease severity in successive generations. Thus, in some cases offspring of affected HD patients have been found to present at an earlier age than their affected parent and to have their disease progress more rapidly than that of the affected parent.

Further expansion of the CAG repeat occurs much more frequently with paternal transmission than maternal transmission of the HD CAG repeat mutation. Thus, this increased tendency to further expansion upon paternal transmission accounts for the observation that about 90% of juvenile HD patients have inherited their disease repeat from an affected father.

http://path.upmc.edu/divisions/neuropath/bpath/cases/case17.html

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