The challenge of juvenile Huntington disease

Abstract

In a cohort of patients with suspected juvenile-onset Huntington disease (HD), we compared HD expansion-positive and -negative cases in order to identify parameters that may allow differentiating between them and may act as a guide to clinicians contemplating genetic testing. We analyzed the clinical and genetic characteristics of 76 juvenile-onset patients referred consecutively for HD genetic testing over a 16-year period. In total, 24 patients were positive for the HD expansion (7.8% of our HD cohort). Mean age at onset of expanded cases was similar to unexpanded cases. All expanded cases had a family history of genetically confirmed HD compared to only 13.5% of unexpanded cases (p = 0.000). Clinical symptoms at onset or at presentation could not differentiate between expanded and unexpanded patients. Although criteria suggested by previous reports allowed statistical differentiation between the 2 groups, they were not sufficiently sensitive and specific to be used in clinical context and performed less satisfactorily than presence of a family history of HD alone. A diagnosis of juvenile HD should be primarily contemplated in symptomatic children with a family history of HD, although a proportion of these will test negative. With no family history of HD, juvenile HD is very unlikely and genetic testing should never delay searching for other causes. The specific nature of symptoms at onset or at presentation is of limited value in guiding the decision to test or not to test.