PDF Ebook Huntington’s disease: Where are we and where should we be?
Huntington’s disease (HD) is a progressive, neurodegenerative disorder with an autosomal-dominant (see Figure 3a) pattern of inheritance. Anyone carrying the mutation responsible for the pathogenesis of HD will ultimately develop the disease. This disease is generally late-onset and characterized by psychiatric, cognitive, and motor disturbances due to progressive neurodegeneration in the cerebral cortex and basal ganglia (Landles & Bates, 2004). As the disease progresses, the individual becomes bed or wheelchair bound. This functional decline is followed by death anywhere between 10 to 25 years after the onset of disease. Death has been known to result from various possible sequelae due to the effects of disease process such as malnutrition, aspiration pneumonia, cardiac complications, and many others.
Worldwide incidence is estimated to be between 4 and 5 per million, but is more prevalent in certain countries (Brown & Ropper, 2005). Malta and Norway have rates that are higher than others while countries like Finland and Japan have a decreased prevalence (Harper, 1992). Specifically in Finland, the prevalence falls to 5 per million being affected (Palo, Somer, Ikonen, Karila, & Peltonen, 1987). Venezuela is another area with increased prevalence of HD (Wexler, 2004). With so many lives affected by HD, it is important to gain better understanding of the disorder. This paper discusses characteristics and hereditability of HD, pathogenesis, predictive and prenatal testing, as well as current treatment options and ideas for future research. With increase in knowledge comes the higher likelihood of discovering a cure.
Symptoms of Huntington’s disease can be nonspecific and include a wide range of personality or mood changes, dementia, and the hallmark choreiform movements. Irritability, depression, aggressive tendencies, and impulsive actions can all be a part of the personality changes associated with HD (Gusella & Macdonald, 2006). Chorea involves involuntary jerky movements of the whole body. The disease symptoms occur because of a mutation that causes more than 36 CAG (glutamate) trinucleotide repeats to occur on a portion of the IT15 gene located on chromosome 4p16.3 (Kremer et al., 1994; Landles & Bates, 2004). The expanded sequence causes a polyglutamine tail to be added to the huntingtin protein (htt) when the mRNA from the altered gene is translated (Landles & Bates, 2004). The polyglutamine tail is located on the 5’ end of the htt protein (Gusella & Macdonald, 2006). A conformational change in the protein’s structure occurs that appears to be directly related to the change in its function (Landles & Bates, 2004). The length of the trinucleotide repeat and age at the time of onset are inversely related (Gusella & Macdonald, 2006). As the mutation is passed from one generation to the next, alterations in the length of the CAG repeat may occur (Gusella & MacDonald, 1994). This may either increase or decrease the age of onset observed for individuals in that generation.
Most cases of Huntington’s disease involve onset in middle age. However, there is also the possibility that onset can occur much sooner in life. The actual age range for HD onset is anywhere from as young as 2 years to as old as 85 years. While CAG repeat length may influence the timing of onset, it seems to have very little, if anything, to do with the timeline of progression for the disease symptoms (Gusella & Macdonald, 2006). The symptoms that a patient presents with seem to differ depending on his or her age at the time. In order to be diagnosed with Juvenile Huntington’s Disease (JHD), onset of symptoms must begin before the age of 20 (Ribai et al., 2007). The symptoms that a juvenile onset patient may present with commonly include slowed speech and awkward gait (Kirkwood, Su, Conneally, & Foroud, 2001). Patients with JHD tend to have increased severity in symptoms such as bradykinesia, abnormal eye movements, and dystonia (Louis, Anderson, Moskowitz, Thorne, & Marder, 2000). Epileptic seizures and rigidity have also been associated with earlier age of onset, whereas the late onset forms of the disease have been associated more with choreiform movements (Siesling, Vegter-van der Vlis, & Roos, 1997). Rigidity may be the most distinguishing feature of an individual with JHD (Van Dijk, Van der Velde, Roos, & Bruyn, 1986).
Contents
Introduction
Genetic Transmission
Pathophysiology
Predictive Testing
Prenatal Testing
Where We Are
Where We Are Going
Conclusion
References
Tables
Figures
Abstract
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PDF Ebook Huntington’s disease: Where are we and where should we be?
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