Confirmation of subtle motor changes among presymptomatic carriers of the Huntington disease gene

To confirm that subtle changes in motor function and reaction time are present in presymptomatic individuals carrying the expanded Huntington disease (HD) allele.

A case-control, double-blind study comparing presymptomatic HD gene carriers (PSGCs) and nongene carriers (NGCs) at risk for HD.

The Department of Medical and Molecular Genetics at a general clinical research center in a midwestern city.

Two hundred sixteen individuals at risk for HD who were asymptomatic by self-report and who did not have manifest HD on results of clinical examination, including PSGCs (n = 61) and NGCs (n = 155).

Molecular testing was used to determine the number of CAG repeats in the HD gene. A quantified neurologic examination and a battery of physiological measures of central nervous system function measuring speed of movement and reaction time were administered.

On neurologic examination, the PSGCs exhibited significantly more definite or possible abnormalities than NGCs for overall oculomotor function, saccade velocity, optokinetic nystagmus, chorea of the extremities, and dystonia of the extremities (P<.05). The PSGCs also had significantly slower performance for auditory reaction time, visual reaction time, visual reaction time with decision, movement time, movement time with decision, and button-tapping time, compared with the NGCs (P<.05).

Subtle changes in motor function, speed of movement, and reaction time are present in HD gene carriers who do not exhibit definite choreiform movements and who do not have sufficient signs to make a clinical diagnosis of HD. In addition, a trend toward slower speed of movement and reaction time was observed among this population as their neurologic abnormalities increased.