PREDICTORS OF DIAGNOSIS IN HUNTINGTON’S
DISEASE
The disease first
described by George Huntigton is caused by degeneration of neurons in the basal
ganglia followed by cortical regions, leading clinically to involuntary
movements (chorea), psychiatric symptoms and dementia. Nearly 90% of Huntigton’s
Disease (HD) cases are hereditary and are transmitted in an autosomal dominant
fashion. The other 10% are considered de novo.
The genetic locus
underlying HD was originally mapped to chromosome 4q16 solely via the genetic
analyses of DNA variants. Ten years later the gene responsible for HD was
identified as encoding a 350 kDA protein (huntingtin) and containing a poly-CAG
repeats in exon 1.
Subtle objective signs and
subjective symptoms of HD are often present before the neurologic disease is
clinically manifest, Langbehn, Paulsen & Huntington Study Group examined the
prognostic significance of these early clinical clues (Langbehn, Paulsen
& Huntington Study Group, Predictors of diagnosis in Huntington disease. Neurology
68, 1710-1717, 2007).
Authors analysed longitudinal
data from 218 at-risk but healthy participants in the Huntington Study Group database
who had either normal motor examination results or minimal soft motor signs at
first observation.
As the researchers state
in their abstract, findings demonstrate that neuropsychological performance and
both the clinician rating and the patient subjective perception of motor
difficulties contribute to a prediction of HD diagnosis. These findings may have
implication for prognostic assessment of persons at risk and eventually assist with
early interventions.