Thomas Cronin1,2, Anne Rosser3,2,4, Thomas Massey2,4. 1. Institute of Neuroscience, Newcastle University, Newcastle, UK. 2. MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK. 3. Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, UK. 4. Brain Research and Intracranial Neurotherapeutics (BRAIN) unit.
Abstract
BACKGROUND: Juvenile-onset Huntington's disease (JHD) is defined by onset at the age of 20 or younger and represents approximately 5% of all HD cases. Patients with JHD present with a broad range of symptoms and signs that only overlap partially with adult-onset HD. A greater awareness and understanding of the presentation of JHD would improve the diagnosis and treatment of this condition. OBJECTIVE: To undertake a systematic review of the literature relating to the clinical features at first presentation of JHD. METHODS: We searched MEDLINE and EMBASE for all studies describing presenting features of JHD patients, performed quality control, and collated and analysed the data. RESULTS: We screened 2917 records for eligibility, and included 79 studies (n = 285 individuals) in the analysis. All were case reports and case series, synthesising data from 25 different countries. Thirty-four different clinical features at presentation were identified. Four groups of symptoms or signs were present in more than 15% of cases: behavioural disturbance, falls/gait disturbance, cognitive impairment and parkinsonian features. Where data were available, the median age of onset was 9 years, 52% were female, the mutant HTT allele was transmitted paternally in 80% of cases, and the median CAG repeat length was 64. CONCLUSIONS: JHD can present with a wide variety of symptoms and signs, with non-motor characteristics being observed most frequently. Greater recognition of these presentations will facilitate early diagnosis and management. Tailored rating scales to score motor, non-motor, and functional impairments specifically in JHD are required to standardise research studies, and are under development.
BACKGROUND: Juvenile-onset Huntington's disease (JHD) is defined by onset at the age of 20 or younger and represents approximately 5% of all HD cases. Patients with JHD present with a broad range of symptoms and signs that only overlap partially with adult-onset HD. A greater awareness and understanding of the presentation of JHD would improve the diagnosis and treatment of this condition. OBJECTIVE: To undertake a systematic review of the literature relating to the clinical features at first presentation of JHD. METHODS: We searched MEDLINE and EMBASE for all studies describing presenting features of JHD patients, performed quality control, and collated and analysed the data. RESULTS: We screened 2917 records for eligibility, and included 79 studies (n = 285 individuals) in the analysis. All were case reports and case series, synthesising data from 25 different countries. Thirty-four different clinical features at presentation were identified. Four groups of symptoms or signs were present in more than 15% of cases: behavioural disturbance, falls/gait disturbance, cognitive impairment and parkinsonian features. Where data were available, the median age of onset was 9 years, 52% were female, the mutant HTT allele was transmitted paternally in 80% of cases, and the median CAG repeat length was 64. CONCLUSIONS: JHD can present with a wide variety of symptoms and signs, with non-motor characteristics being observed most frequently. Greater recognition of these presentations will facilitate early diagnosis and management. Tailored rating scales to score motor, non-motor, and functional impairments specifically in JHD are required to standardise research studies, and are under development.
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