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Review
. 2024;13(2):149-161.
doi: 10.3233/JHD-231523.

Clinical Review of Juvenile Huntington's Disease

Mayke Oosterloo  1   2 , Alexiane Touze  3 , Lauren M Byrne  3 , Jannis Achenbach  4 , Hande Aksoy  5 , Annabelle Coleman  3 , Dawn Lammert  6 , Martha Nance  7 , Peggy Nopoulos  8 , Ralf Reilmann  9   10 , Carsten Saft  4 , Helen Santini  11 , Ferdinando Squitieri  12   13 , Sarah Tabrizi  3 , Jean-Marc Burgunder  14 , Oliver Quarrell  15   16 ; Pediatric Huntington Disease Working Group of the European Huntington Disease Network
Affiliations
Review

Clinical Review of Juvenile Huntington's Disease

Mayke Oosterloo et al. J Huntingtons Dis. 2024.

Abstract

Juvenile Huntington's disease (JHD) is rare. In the first decade of life speech difficulties, rigidity, and dystonia are common clinical motor symptoms, whereas onset in the second decade motor symptoms may sometimes resemble adult-onset Huntington's disease (AOHD). Cognitive decline is mostly detected by declining school performances. Behavioral symptoms in general do not differ from AOHD but may be confused with autism spectrum disorder or attention deficit hyperactivity disorder and lead to misdiagnosis and/or diagnostic delay. JHD specific features are epilepsy, ataxia, spasticity, pain, itching, and possibly liver steatosis. Disease progression of JHD is faster compared to AOHD and the disease duration is shorter, particularly in case of higher CAG repeat lengths. The diagnosis is based on clinical judgement in combination with a positive family history and/or DNA analysis after careful consideration. Repeat length in JHD is usually > 55 and caused by anticipation, usually via paternal transmission. There are no pharmacological and multidisciplinary guidelines for JHD treatment. Future perspectives for earlier diagnosis are better diagnostic markers such as qualitative MRI and neurofilament light in serum.

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Conflict of interest statement

During the past year, Mayke Oosterloo has received research grant funding from NWA-ORC (NWA.1389.20.244) and a pending patent (EP23197746.3). Mayke Oosterloo is on the scientific advisory board of the European Huntington Disease Network.

Martha Nance’s institution, Health Partners, receives program funding from Parkinson’s Foundation and for research activities from BIAL. Her institution, Hennepin HealthCare Institute, receives support from the Huntington Disease Society of America. In the last year, she has been compensated for consulting activities by F. Hoffman-La Roche, Neurocrine, Novartis, Sage Therapeutics, Uniqure Biopharma, and for service on Steering Committees for research studies funded by Neurocrine, BIAL, and Parkinson’s Foundation. She is a member of the Executive Membership Committee of the Huntington Study Group.

Peggy Nopoulos receives funds from the National Institute of Health (NIH) to prospectively study subjects with JHD in a natural history program (no intervention). She is also a paid consultant for the companies Annexon, Prilenia, and Unicure.

Ralf Reilmann is founding director and owner of the George-Huntington-Institute, a private research institute focused on clinical and preclinical research in Huntington’s disease, and QuantiMedis, a clinical research organization providing Q-Motor (quantitative motor) services in clinical trials and research. Dr. Reilmann has provided consulting services, advisory board functions, clinical trial services, quantitative motor analyses, and/or lectures for Actelion, Alnylam, Amarin, AOP Orphan Pharmaceuticals, AskBio, Cure Huntington Disease Initiative Foundation (CHDI), Desitin, Hoffmann-La Roche, IONIS, Ipsen, Lundbeck, MEDA Pharma, Medivation, Mitoconix, Neurocrine, Neurosearch, Novartis, Omeros, Pfizer, Prana Biotechnology, Prilenia, PTC Therapeutics, Raptor, Sage, Siena Biotech, Solaxa, Temmler Pharma, Teva, uniQure, Vaccinex, Voyager, Wave Life Sciences, and Zevra. He has received grant support from the Bundesministerium für Bildung und Forschung (BMBF), the Cure Huntington Disease Initiative Foundation (CHDI), the Deutsche Forschungsgemeinschaft (DFG), the Deutsches Zentrum für Neurodegeneration und Entzündung (DZNE), the European Union’s 7th Framework Program (EU-FP7) and Horizon2020 Innovative Medicine Initiative 2 program (IMI2), the European Huntington Disease Network (EHDN), the High-Q-Foundation, the National Institute of Health (NIH), and the National Science Foundation (NSF).

Fernando Squitieri received remuneration as member of the scientific advisory board of PTC Therapeutics and Prilenia.

Sarah J. Tabrizi received research grant funding from the Wellcome Trust (223082/Z/21/Z), and the UK Dementia Research Institute that receives its funding from DRI Ltd., funded by the UK MRC, Alzheimer’s Society, and Alzheimer’s Research UK and from the CHDI Foundation and the UK Medical Research Council. Through the offices of UCL Consultants Ltd, a wholly owned subsidiary of University College London, Sarah J. Tabrizi has undertaken consultancy services for Alnylam Pharmaceuticals, Annexon, Ascidian Therapeutics, Arrowhead Pharmaceuticals, Atalanta Therapeutics, Design Therapeutics, F. Hoffman-La Roche, Iris Medicine, Latus Bio, LifeEdit, Novartis Pharma, Pfizer, Prilenia Neurotherapeutics, PTC Therapeutics, Rgenta Therapeutics, Takeda Pharmaceuticals, UniQure Biopharma, Vertex Pharmaceuticals. In the past 12 months, University College London Hospitals NHS Foundation Trust, Professor Tabrizi’s host clinical institution, received funding to run clinical trials for F. Hoffman-La Roche, Novartis Pharma, PTC Therapeutics, and UniQure Biopharma.

Martha Nance, Peggy Nopoulos, Ralf Reilmann, Carsten Saft, Ferdinando Squitieri, Sarah Tabrizi, and Oliver Quarrell are Editorial Board members of this journal, but were not involved in the peer-review process nor had access to any information regarding its peer review. The other authors have no conflict of interest to report.

References

    1. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. The Huntington’s Disease Collaborative Research Group. Cell. 72(6):971–83. - PubMed
    1. Roos RA. Huntington’s disease: A clinical review. Orphanet J Rare Dis. 2010;5:40. - PMC - PubMed
    1. Vinken PJ, Bruyn GW. Huntington’s chorea: Historical, clinical and laboratory synopsis. Handbook of clinical neurology. The Netherlands: Elsevier. 1968.
    1. Hoffmann J. On chronic progressive chorea (Huntington’s chorea, hereditary chorea). Virchows Arch A Pathol Anat. 1888;111, 513–48.
    1. Westphal C. Ueber eine dem Bilde der cerebrospinalen grauen Degeneration ähnliche Erkrankung des centralen Nervensystems ohne anatomischen Befund, nebst einigen Bemerkungen über paradoxe Contraction. Arch Psychiatr Nervenkrank. 1883;14.

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