The onset and prevalence of motor and psychiatric symptoms in Huntington's disease

Background: Huntington9s disease is characterised by a range of motor, psychiatric and cognitive symptoms. These present in different combinations through the disease course and impact on daily life and functioning. Huntington9s disease is caused by a dominant CAG repeat expansion in the HTT gene, and longer repeats are associated with earlier onset of motor symptoms. Objectives: To investigate the onset, prevalence and functional impact of motor and psychiatric symptoms of Huntington9s disease. Methods: We analysed clinical phenotype data from the European REGISTRY study for 6316 individuals with manifest Huntington9s disease. Onset and prevalence data for motor and psychiatric symptoms were extracted from the clinical history part of REGISTRY and the detailed Clinical Characteristics Questionnaire. Generalised linear models were constructed to assess relationships between symptoms and functional outcomes. Results: As age at first presentation of Huntington9s disease increases, the likelihood that the initial presenting symptom is motor also increases. This is not associated with pathogenic CAG repeat length. At a population level there were conserved relationships between symptoms across different repeat lengths, with depression often occurring early followed by motor and then cognitive symptoms. There were significant relationships between all individual psychiatric and cognitive symptoms and reduced functional capacity. Conclusions: There are conserved patterns of symptoms in HD that can be quantified. Psychiatric and behavioural symptoms significantly impair daily functioning and should be considered part of the disease trajectory at any age.