Huntington disease is an autosomal dominant neurodegenerative disorder.
Often presents in midlife but may appear at any age.
Clinical manifestations include chorea, cognitive decline, loss of coordination, and personality change.
Depression and suicide may be comorbid events.
In the absence of available effective treatment, many at-risk individuals forgo predictive genetic testing.
Huntington disease is a slowly progressive, neurodegenerative disorder characterized by chorea, incoordination, cognitive decline, personality changes, and psychiatric symptoms, culminating in immobility, mutism, and inanition. It is an autosomal dominant, trinucleotide repeat disorder that affects men and women equally. It characteristically appears in mid-adult life but can occur at any age. Treatment for depression, and to some degree behavioral problems and chorea, is possible. There are no disease-modifying therapies.
History and exam
Key diagnostic factors
- positive family history of Huntington disease
- known expansion of the CAG repeat length at the N-terminal end of the huntingtin gene
- impaired work or school performance
- personality change
- irritability and impulsivity
- twitching or restlessness
- loss of coordination
- deficit in fine motor coordination
- slowed rapid (saccadic) eye movements
- motor impersistence
- impaired tandem walking
Other diagnostic factors
- concentration impairment/task anxiety or apathy
- cognitive decline relative to spouse/siblings
- changes in personal habits/hygiene
- disinhibition or unusually anxious behavior
- depression, obsessions, and compulsions
- expansion of the CAG repeat length at the N-terminal end of the huntingtin gene
- other genetic factors
- family history
1st investigations to order
- no initial tests
Investigations to consider
- CAG repeat testing
- MRI or CT scan
Mitsuko Nakajima, MD
Clinical Research Fellow
Huntington's Disease Centre
Institute of Neurology
Department of Neurodegenerative Disease
Russell Square House
MN declares no competing interests.
Dr Mitsuko Nakajima would like to gratefully acknowledge Dr Peter McColgan, Dr Sarah Tabrizi, Dr David Craufurd, Dr Marianne Novak, and Dr Francis Walker, previous contributors to this topic.
FW declared that he had no competing interests. MN is an author of a reference cited in this topic. DC has received fees for advisory board membership from Hoffmann-La Roche Ltd. SJT has received grant funding for her research from CHDI Foundation, the BBSRC, Dementia and Neurodegenerative Disease Network UK, European Huntington’s Disease Network, Huntington’s Disease Association of the UK, the Medical Research Council UK, Takeda Pharmaceuticals, the UCL/UCLH Biomedical Research Center, and the Wellcome Trust. SJT has been on advisory boards or had consultancies with F. Hoffmann-La Roche Ltd, Ixico Technologies, Shire Human Genetic Therapies, Takeda Pharmaceuticals International, and TEVA Pharmaceuticals; all honoraria for these consultancies and advisory boards were paid to UCL. Through the offices of UCL Consultants Ltd, a wholly owned subsidiary of UCL, SJT has undertaken consultancy services for F. Hoffmann-La Roche Ltd and GSK. ST is also an author of references cited in this topic PM declared that he had no competing interests.
Adrian Priesol, MD, FRCPC
Massachusetts Eye and Ear Infirmary
Harvard Medical School
AP declares that he has no competing interests.
Tiago Mestre, MD, MSc
Neurological Clinical Research Unit
Institute of Molecular Medicine
TM declares that he has no competing interests.
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