Subtle changes among presymptomatic carriers of the Huntington's disease gene

Objectives-To compare the neurological and psychometric characteristics of presymptomatic gene carriers and non-gene carriers who are at risk for deve loping Huntington's disease so as to characterise early signs of disease an d to identify markers of neurological function that could be used to assess the impact of experimental therapies on the progression of disease, even a mong those who are clinically presymptomatic. Methods-A sample of people at risk for Huntington's disease was genotyped a nd evaluated using subscales of the Wechsler adult intelligence scale-revis ed (WAIS-R), a quantified neurological rating scale, and computerised physi ological measures including speed of movement and reaction time. Results-Genotyping and clinical examination determined that 171 participant s were presymptomatic gene carriers (PSGCs) and 414 participants were non-g ene carriers (NGCs). The PSGCs performed significantly worse when compared with the NGCs on the digit symbol, picture arrangement, and arithmetic subs cales of the WAIS-R (p<0.02) and for the physiological measures: button tap ping, auditory reaction time, visual reaction time with decision, and movem ent time with and without decision (p<0.05). Although no PSGCs had sufficie nt neurological findings to warrant a diagnosis of Huntington's disease on clinical examination, the PSGCs had more frequent possible or definite abno rmality for oculomotor function, chorea, muscle stretch reflexes, gait, and station stability, and rapid alternating movements (p less than or equal t o0.02). Conclusions-Among Huntington's disease gene carriers, subtle cognitive and motor deficits precede the onset of sufficient neurological abnormality to warrant a clinical diagnosis of Huntington's disease.