High incidence rate and absent family histories in one quarter of patientsnewly diagnosed with Huntington disease in British Columbia

The advent of the direct mutation test for Huntington disease (HD) has made it possible to identify a previously unrecognized symptomatic population o f HD, including those with an atypical presentation or patients without a f amily history of HD. The present study investigated the uptake of this test in the province of British Columbia (BC), Canada and assessed the incidenc e rate and rate of identification of new mutations for HD. All symptomatic individuals residing in BC who were referred for the genetic test for HD be tween 1993 and 2000 (n = 205) were analyzed for CAG expansion, baseline dem ographics and clinical data, and a family history of HD. A total of 141 (or 68.8%) had a CAG expansion greater than or equal to 36. Of these, almost o ne-quarter (24.1%) did not have a family history of HD. An extensive chart review revealed that 11 patients (or 7.8%) had reliable information on both parents (who lived well into old age) and therefore possibly could represe nt new mutations for HD, This indicates a three to four times higher new mu tation rate than previously reported. Our findings also show that the yearl y incidence rate for HD was 6.9 per million which, is two times higher than previous incidence studies performed prior to the identification of the HD mutation. We also identified five persons with a clinical presentation of HD but without CAG expansion (geno-copies) (2.4%).