2011 Group Project 4

From Embryology
Note - This page is an undergraduate science embryology student group project 2011.
2011 Projects: Turner Syndrome | DiGeorge Syndrome | Klinefelter's Syndrome | Huntington's Disease | Fragile X Syndrome | Tetralogy of Fallot | Angelman Syndrome | Friedreich's Ataxia | Williams-Beuren Syndrome | Duchenne Muscular Dystrolphy | Cleft Palate and Lip

Huntington's Disease


Huntington’s disease (HD) is an autosomal dominant disease that is established by the mutated huntingtin protein gene. HD is characterized by neuronal degeneration and dysfunction of the cerebral cortex and striatum which may be the cause of its clinical manifestations in jerky, involuntary movements such as chorea [1] [2].


Huntington's disease has existed since at least the seventeenth century and several physicians provided earlier descriptions of hereditary chorea but without much detail. In 1872, Huntington’s disease was first documented with great details by George Huntington in “On Chorea”[3]. Huntington’s disease was initially known as chorea, derived from the Greek word “khoreia” which means dancing in unison.

George Huntington described the disease as “an heirloom from generations away back in the dim past” as he realized that HD was hereditary. This conclusion was reached when he observed that if one of the parents had the disease, the offspring will inevitably have the disease too. In his paper, “On Chorea”, he described:

"Of its hereditary nature. When either or both the parents have shown manifestations of the disease ..., one or more of the offspring almost invariably suffer from the disease ... But if by any chance these children go through life without it, the thread is broken and the grandchildren and great-grandchildren of the original shakers may rest assured that they are free from the disease.".[4]

Huntington thus was able to explain the precise pattern of inheritance of autosomal dominant disease years before the rediscovery by scientists of Mendelian inheritance.


There seem to be an increased prevalence of Huntington's disease among white people as compared to Africans and Asians. For those areas where there are intermarriages with white people, there is a higher occurence of the disease. This is related to the higher frequency of huntingtin alleles with 28–35 CAG repeats in white individuals and the fact the disease is autosomal dominant. [5]

Pathogenesis and Genetics

Diagnostic Tests

Huntington’s Disease is most commonly diagnosed at the onset on symptoms, typically in the middle ages. The diagnosis is relatively simple in patients with typical symptoms. Diagnosis is important to ensure that this disease is not confused with similar diseases, which mimic similar characteristics [6]. These include tardive dyskinesia, chorea gravidarum, hyperthyroid chorea and Neuroacanthocytosis [7]. In children, subacute sclerosing panencephalitis can easily be mistaken for Huntington’s disease as they both present with very similar clinical presentations [8]. Huntington’s disease can also be diagnosed when a patient is asymptomatic, by genetic testing. This also enables detection of the disease in embryos.


Anton (1896) and Lannois (1897) were the first to observe neuropathological changes associated with Huntington’s disease. They independently noted the degeneration of the striatum in patients with Huntington’s disease [9]. Numerous other neuropathological abnormalities have now been identified in different parts of the brain including the subtalamic regions, pons and medulla oblongata, the spinal cord, amygdala, cerebellum, superior olive as well as the claustrum [10]. The neuropathological hallmark of Huntington’s disease is now know to be the gradual loss of spiny GABAergic projection neurons of the neostriatum. This is accompanied with the atrophy of the caudate of nucleus, putamen and external segment of the globus pallidus [11].

Clinical Manifestations


There is no cure for Huntington's disease. Similar to AIDS, only the symptoms can be treated to slow down the progression of the disease.


  • Movement disorders
  • Psychiatric disorders


  • Psychotherapy
  • Speech Therapy
  • Physical Therapy
  • Occupational Therapy


Quite recently, there are a couple of breakthroughs for the treatment of Huntington's.

  • Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's disease patients. [12]
  • Using adult neurotrophic factor-secreting stem cells. [13]

Current/Future Research

The main area for future research into Huntington’s disease is aimed at finding therapeutic ways to treat the disease in the asymptomatic phase. Research is also being done into finding treatment options to cure symptoms at different stages of the disease. Animal models (mouse) have been used since the 1970s [14] to demonstrate the degenerative progression of the disease. They also provide biological, histopathological and cell-to-cell evidence which allow for the basis of finding treatment options as well as allowing us to see the effects of gene modification.

External Links



  1. <pubmed>21841917</pubmed>
  2. <pubmed>21847326</pubmed>
  3. Huntington G (1872). "On Chorea". Medical and Surgical Reporter of Philadelphia (The Hague: Nijhoff) 26 (15): 317–321. ISBN 9061860113. [1]
  4. <pubmed>11232352</pubmed>
  5. DC Rubinsztein, Molecular biology of Huntington's disease (HD) and HD-like disorders. In: S Pulst, Editor, Genetics of movement disorders, Academic Press, California (2003), pp. 365–377.
  6. <pubmed>17240289</pubmed>
  7. <pubmed>16003113</pubmed>
  8. <pubmed>11807185</pubmed>
  9. <pubmed>2147116</pubmed>
  10. <pubmed>2932539</pubmed>
  11. <pubmed>21496571</pubmed>
  12. <pubmed>19361997</pubmed>
  13. <pubmed>19603590</pubmed>
  14. <pubmed>8731</pubmed>

2011 Projects: Turner Syndrome | DiGeorge Syndrome | Klinefelter's Syndrome | Huntington's Disease | Fragile X Syndrome | Tetralogy of Fallot | Angelman Syndrome | Friedreich's Ataxia | Williams-Beuren Syndrome | Duchenne Muscular Dystrolphy | Cleft Palate and Lip