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

Objective: To confirm that subtle changes in motor function and reaction ti me are present in presymptomatic individuals carrying the expanded Huntingt on disease (HD) allele. Design: A case-control, double-blind study comparing presymptomatic HD gene carriers (PSGCs)and non-gene carriers (NGCs) at risk for HD. Setting: The Department of Medical and Molecular Genetics at a general clin ical research center in a midwestern city. Participants: Two hundred sixteen individuals at risk for HD who were asymp tomatic by self-report and who did not have manifest HD on results of clini cal examination, including PSGCs (n=61) and NGCs (n=155). Measures: Molecular testing was used to determine the number of CAG repeats in the HD gene. A quantified neurologic examination and a battery of physi ological measures of central nervous system function measuring speed of mov ement and reaction time were administered. Results: On neurologic examination, the PSGCs exhibited significantly more definite or possible abnormalities than NGCs for overall oculomotor functio n, saccade velocity, optokinetic nystagmus, chorea of the extremities, and dystonia of the extremities (P<.05). The PSGCs also had significantly slowe r performance for auditory reaction time, visual reaction time, visual reac tion time with decision, movement time, movement time with decision, and bu tton-lapping time, compared with the NGCs (P<.05). Conclusions: Subtle changes in motor function, speed of movement, and react ion time are present in HD gene carriers who do not exhibit definite chorei form movements and who do not have sufficient signs to make a clinical diag nosis of PID. In addition, a trend toward slower speed of movement and reac tion time was observed among this population as their neurologic abnormalit ies increased.