Affiliations: [a] Institute of Neuroscience, Newcastle University, Newcastle, UK
| [b] Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, UK
| [c] MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
| [d]
Brain Research and Intracranial Neurotherapeutics (BRAIN) unit
Correspondence:
[*]
Correspondence to: Thomas Massey, MRC Centre for Neuropsychiatric Genetics and Genomics, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK. Tel.: +44 2920 688353; E-mail: [email protected].
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.
