Huntington's Disease

 

 Buy Article Permissions and Reprints

ABSTRACT

Huntington's disease may present at any age, but most typically manifests between the ages of 35 and 45 years as a slowly progressive neurodegenerative movement disorder with cognitive and behavioral impairment. It is an autosomal-dominant disorder that has a substantial impact on family structure and dynamics in terms of providing care for affected family members and, for the offspring of an affected parent, dealing with at-risk status. Therapy that slows the progressive neuronal dysfunction or degeneration is unavailable, so pharmacotherapy is currently aimed primarily at managing behavioral and psychiatric symptoms, and, in selected cases, controlling severe chorea. Effective intervention by clinicians is possible, however, in terms of providing patients and families with accurate information about the disease, counseling them about availability of genetic testing at specialized centers, and in giving them sound advice regarding work, driving, relationships, finances, research participation, and support groups.

REFERENCES

• 1 Rubinsztein D C, Leggo J, Coles R et al.. Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats.  Am J Hum Genet. 1996;  59 16-22
  PubMedGoogle Scholar
• 2 Ranen N G, Stine O C, Abbott M H et al.. Anticipation and instability of IT-15(CAG)n repeats in parent-offspring pairs with Huntington's disease.  Am J Hum Genet. 1995;  57 593-602
  PubMedGoogle Scholar
• 3 Kremer B, Almqvist E, Theilmann J et al.. Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes.  Am J Hum Genet. 1995;  57 343-350
  PubMedGoogle Scholar
• 4 Andrew S E, Goldberg Y P, Kremer B et al.. The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease.  Nat Genet. 1993;  4 398-403
  CrossrefPubMedGoogle Scholar
• 5 The Huntington's Disease Collaborative Research Group . A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes.  Cell. 1993;  72 971-983
  CrossrefPubMedGoogle Scholar
• 6 Wexler N S, Lorimer J, Porter J et al.. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset.  Proc Natl Acad Sci USA. 2004;  101 3498-3503
  CrossrefPubMedGoogle Scholar
• 7 Harper P S, Jones L. Huntington's disease: genetic and molecular studies. In: Bates G, Harper P, Jones L Huntington's Disease. New York; Oxford University Press 2002: 113-158
  Google Scholar
• 8 Rubinsztein D C. Molecular biology of Huntington's disease (HD) and HD-like disorders. In: Pulst S Genetics of Movement Disorders. San Diego; Academic Press 2003: 365-377
  Google Scholar
• 9 Takano H, Cancel G, Ikeuchi T et al.. Close associations between prevalences of dominantly inherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian populations.  Am J Hum Genet. 1998;  63 1060-1066
  CrossrefPubMedGoogle Scholar
• 10 Pridmore S A. The large Huntington's disease family of Tasmania.  Med J Aust. 1990;  153 593-595
  PubMedGoogle Scholar
• 11 The World Federation of Neurology Research Group on Huntington's Disease . Presymptomatic testing for Huntington's disease: a world-wide survey.  J Med Genet. 1993;  30 1020-1022
  PubMedGoogle Scholar
• 12 Creighton S, Almqvist E W, MacGregor D et al.. Predictive, pre-natal and diagnostic genetic testing for Huntington's disease: the experience in Canada from 1987-2000.  Clin Genet. 2003;  63 462-475
  CrossrefPubMedGoogle Scholar
• 13 Timman R, Roos R, Maat-Kievit A, Tibben A. Adverse effects of predictive testing for Huntington disease underestimated: long-term effects 7-10 years after the test.  Health Psychol. 2004;  23 189-197
  CrossrefPubMedGoogle Scholar
• 14 Almqvist E W, Brinkman R R, Wiggins S, Hayden M R. Canadian Collaborative Study of Predictive Testing . Psychological consequences and predictors of adverse events in the first 5 years after predictive testing for Huntington's disease.  Clin Genet. 2003;  64 300-309
  CrossrefPubMedGoogle Scholar
• 15 International Huntington Association (IHA) and the World Federation of Neurology (WFN) Research Group on Huntington's Chorea . Guidelines for the molecular genetics predictive test in Huntington's disease.  Neurology. 1994;  44 1533-1536
  PubMedGoogle Scholar
• 16 Gutekunst C, Norflus F, Hersch S. The neuropathology of Huntington's disease. In: Bates G, Harper P, Jones L Huntington's Disease. New York; Oxford University Press 2002: 251-275
  Google Scholar
• 17 Graham R K, Deng Y, Slow E G et al.. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin.  Cell. 2006;  125 1179-1191
  CrossrefPubMedGoogle Scholar
• 18 Wanker E, Droge A. Structural biology of Huntington's disease. In: Bates G, Harper P, Jones L Huntington's Disease. New York; Oxford University Press 2002: 327-347
  Google Scholar
• 19 Panov A V, Burke J R, Strittmatter W J, Greenamyre J T. In vitro effects of polyglutamine tracts on a Ca2 + dependent depolarization of rat and human mitochondria: relevance to Huntington's disease.  Arch Biochem Biophys. 2003;  410 1-6
  CrossrefPubMedGoogle Scholar
• 20 Charrin B C, Saudou F, Humbert S. Axonal transport failure in neurogenerative disorders: the case of Huntington's disease.  Pathol Biol. 2005;  53 189-192
  CrossrefPubMedGoogle Scholar
• 21 Cha J H. Transcriptional dysregulation in Huntington's disease.  Trends Neurosci. 2000;  23 387-392
  CrossrefPubMedGoogle Scholar
• 22 Rangone H, Humbert S, Saudou F. Huntington's disease: how does huntingtin, an anti-apoptotic protein, become toxic?.  Pathol Biol. 2004;  52 338-342
  CrossrefPubMedGoogle Scholar
• 23 Duan W, Guo Z, Jiang H et al.. Paroxetine retards disease onset and progression in Huntingtin mutant mice.  Ann Neurol. 2004;  55 590-594
  CrossrefPubMedGoogle Scholar
• 24 Bae B I, Xu H, Igarashi S et al.. P53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease.  Neuron. 2005;  47 29-41
  CrossrefPubMedGoogle Scholar
• 25 Freeman W, Morton A J. Regional and progressive changes in brain expression of complexin II in a mouse transgenic for the Huntington's disease mutation.  Brain Res Bull. 2004;  63 45-55
  CrossrefPubMedGoogle Scholar
• 26 Hickey M A, Chesselet M F. Apoptosis in Huntington's disease.  Prog Neuropsychopharmacol Biol Psychiatry. 2003;  27 255-265
  CrossrefPubMedGoogle Scholar
• 27 Higgins Jr D S. Huntington's disease.  Curr Treat Options Neurol. 2006;  8 236-244
  PubMedGoogle Scholar
• 28 Yamamoto A, Lucas J J, Hen R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease.  Cell. 2000;  101 57-66
  CrossrefPubMedGoogle Scholar
• 29 Montoya A, Price B H, Menear M, Lepage M. Brain imaging and cognitive dysfunctions in Huntington's disease.  J Psychiatry Neurosci. 2006;  31 21-29
  PubMedGoogle Scholar
• 30 Paulsen J S, Conybeare R A. Cognitive changes in Huntington's disease.  Adv Neurol. 2005;  96 209-225
  PubMedGoogle Scholar
• 31 Anderson K E, Marshall F J. Behavioral symptoms associated with Huntington's disease.  Adv Neurol. 2005;  96 197-208
  PubMedGoogle Scholar
• 32 Snowden J S, Craufurd D, Griffiths H L, Neary D. Awareness of involuntary movements in Huntington disease.  Arch Neurol. 1998;  55 801-805
  CrossrefPubMedGoogle Scholar
• 33 Blekher T, Johnson S A, Marshall J et al.. Saccades in presymptomatic and early stages of Huntington disease.  Neurology. 2006;  67 394-399
  CrossrefPubMedGoogle Scholar
• 34 Nance M A. The US Huntington Disease Genetic Testing Group. Genetic testing of children at risk for Huntington's disease.  Neurology. 1997;  49 1048-1053
  CrossrefPubMedGoogle Scholar
• 35 Walker F O. Cultivating simple virtues in medicine.  Neurology. 2005;  65 1678-1680
  CrossrefPubMedGoogle Scholar
• 36 Rebok G W, Bylsma F W, Keyl P M, Brandt J, Folstein S E. Automobile driving in Huntington's disease.  Mov Disord. 1995;  10 778-787
  PubMedGoogle Scholar
• 37 Beglinger L J, Langbehn D R, Duff K et al.. Probability of obsessive and compulsive symptoms in Huntington's disease.  Biol Psychiatry. 2006; July 11 ;  , (Epub ahead of print)
  PubMedGoogle Scholar
• 38 Mahant N, McCusker E A, Byth K, Graham S. Huntington Study Group. Huntington's disease: clinical correlates of disability and progression.  Neurology. 2003;  61 1085-1092
  PubMedGoogle Scholar
• 39 Hunt V P, Walker F O. Dysphagia in Huntington's disease.  J Neurosci Nurs. 1989;  21 92-95
  CrossrefPubMedGoogle Scholar
• 40 Moskowitz C B, Marder K. Palliative care for people with late-stage Huntington's disease.  Neurol Clin. 2001;  19 849-865
  CrossrefPubMedGoogle Scholar
• 41 Walker F O. Huntington's disease.  Lancet. 2007;  369 218-228
  CrossrefPubMedGoogle Scholar
• 42 Bonelli R M, Wenning G K. Pharmacological management of Huntington's disease: an evidence-based review.  Curr Pharm Des. 2006;  12 2701-2720
  CrossrefPubMedGoogle Scholar
• 43 Arciniegas D B, Anderson C A. Suicide in neurologic illness.  Curr Treat Options Neurol. 2002;  4 457-468
  PubMedGoogle Scholar

Francis O WalkerM.D. 

Department of Neurology, Wake Forest University School of Medicine, Medical Center Blvd.

Winston-Salem, NC 27157-1078