DNP 810 Topic 8 Case Study – Cumulative: Part 4

Case Study Part 4: Huntington’s Disease

Huntington’s disease is a rare autosomal dominant progressive neurodegenerative disorderaffecting both children and adults. It is characterized by progressive degeneration of nerve cells in the brain causing emotional problems, loss of thinking ability, and uncontrolled movement (Kim et al., 2020). The signs and symptoms of Huntington’s disease can start presenting at any time, with most cases reported at the ages of between 30 to 40 years. However, when an individual develops the disorder before the age of 20 years, it is referred to as juvenile Huntington’s disease. Development of the disease early in life promotes worsening of the symptoms with a high rate of progression. Several medications have been approved by the FDA for the management of the symptoms of Huntington’s disease. However, the available treatments have failed to prevent mental, behavioral, and physical decline associated with the disease. The purpose of this paper is to provide a comprehensive understanding of Huntington’s disease from prevalence and diagnosis to new treatment approaches and the role of scientific evidence in promoting the management of the disorder.

Huntington’s Disease

Huntington’s disease is a rare brain disorder caused by mutations in the HTT gene, involving a DNA sequence known as CAG trinucleotide repeat. The defect is ‘dominant’ meaning that children born of parents with Huntington’s disease are at higher risk of inheriting the disorder. Studies show that children born of parents with Huntington’s disease have a 50% chance of developing the condition, as well as being able to pass the disease to their children thereafter. According to Long et al. (2018), approximately 3 to 7 per a hundred thousand people of European ancestry are affected by Huntington’s disease. The disorder is however less common among members of some communities such as the Chinese, Japanese, and those of African descent.

There are two main forms of the disorder, known as juvenile Huntington’s disease and adult-onset Huntington disease. Juvenile Huntington’s disease is less common and begins in childhood or adolescence. It is associated with social, mental, and emotional problems. Patients will display symptoms such as drooling, slurred speech, rigidity, frequent falling, clumsiness, and slow movement. Their reasoning ability is normally impaired with declining school performance. As reported by Aziz et al. (2018) seizures develop in 30 to 50% of children diagnosed with juvenile Huntington’s disease. This disorder tends to progress faster as compared to adult-onset Huntington’s disease. Diagnosed patients with this disorder normally live up to 10 to 15 years from the time the symptoms started appearing.

Adult-onset Huntington disease on the other hand is the most common form of the disorder which develops among individuals between the ages of 30 to 40 years. Patients will present with learning problems, poor decision-making, poor coordination, small involuntary movements, depression, and irritability (Tabrizi et al., 2020). As the disease progresses, the involuntary movements become more pronounced as other symptoms worse. Patients diagnosed with adult-onset Huntington’s disease usually live for about 15 to 20 years from the time the first symptoms appeared.

Laboratory Testing

For the diagnosis of Huntington’s disease, the patient’s blood sample will be collected for genetic testing. The test will involve Polymerase chain reaction (PCR) testing and fragment sizing of the cytosine-adenine-guanine (CAG) trinucleotide repeat region of the HTT gene (Kim et al., 2020). These tests can be performed for both the individual with symptoms and the asymptomatic ones with a family history of Huntington’s disease. The results from these tests are normally combined with other neurological and laboratory tests in addition to patient history. The neurological examination will involve testing the patient for motor, sensory and psychiatric symptoms. Neuropsychological testing will involve performing standardized tests to assess the patient’s reasoning, language skills, mental agility, and memory. Brain scans such as electroencephalography (EEG), computer tomography (CT), and magnetic resonance imaging (MRI) may be ordered and reviewed to build on the diagnosis.       

Chromosomal Analysis

As mentioned earlier, Huntington’s disease is moved from one person to another as an autosomal dominant trait. The disorder is associated withrepeat expansion of the CAG trinucleotide in the huntingtin (HTT) gene located on the short arm of chromosome 4p16.3 (Maiuri et al., 2019). Normally, chromosomes have an HTT gene with less than 35 CAG repeats, however, in Huntington’s disease, the HTT gene has more than 36 CAG repeats. For families with a history of Huntington’s disease, chromosomal linkage analysis is recommended for predictive testing to determine if the individual will develop the disorder at some point in their life. To be able to map the disease trait segregating in the family at risk, whole-genome screening with highly polymorphic tetranucleotide-, trinucleotide- and dinucleotide-repeat DNA marker must be performed (DiFiglia, 2020). A positive LOD score obtained for the marker D20S482 on chromosome 20p through a two-point LOD score analysis with the MLINK program was used to indicated increased risks of the disorder. Consequently, through haplotype analysis, researchers were able to note that the gene responsible for the Huntington’s disease was likely located in a 2.7-cM region between D20S193 and D20S895 markers. The candidate genes must be screened for the mutation to confirm the presence of the disease.

Conclusion

Huntington’s disease is an inherited disorder resulting from mutations in the HTT gene, involving a DNA sequence known as a CAG trinucleotide repeat.The disorder is usually diagnosed based on results obtained from genetic testing among other imaging studies such as CT scans and EEG. There is no cure for the disorder, but new treatments have been approved by the FDA and incorporated in clinical treatment guidelines for the management of symptoms displayed by patients with the disease. A comprehensive understanding of the chromosomal analysis and mutations involved in the development of the disease is crucial in advancing research to come up with potential therapeutic options to promote the well-being and health of patients living with the disease.

References

Aziz, N. A., van der Burg, J. M., Tabrizi, S. J., & Landwehrmeyer, G. B. (2018). Overlap between age-at-onset and disease-progression determinants in Huntington disease. Neurology, 90(24), e2099-e2106. https://doi.org/10.1212/WNL.0000000000005690

Kim, K. H., Hong, E. P., Shin, J. W., Chao, M. J., Loupe, J., Gillis, T., … & Lee, J. M. (2020). Genetic and functional analyses point to FAN1 as the source of multiple Huntington disease modifier effects. The American Journal of Human Genetics, 107(1), 96-110. https://doi.org/10.1016/j.ajhg.2020.05.012

Long, J. D., Lee, J. M., Aylward, E. H., Gillis, T., Mysore, J. S., Elneel, K. A., … & Gusella, J. F. (2018). Genetic modification of Huntington’s disease acts early in the prediagnosis phase. The American Journal of Human Genetics, 103(3), 349-357. https://doi.org/10.1016/j.ajhg.2018.07.017

Maiuri, T., Suart, C. E., Hung, C. L. K., Graham, K. J., Barba Bazan, C. A., & Truant, R. (2019). DNA damage repair in Huntington’s disease and other neurodegenerative diseases. Neurotherapeutics, 16(4), 948-956. https://doi.org/10.1007/s13311-019-00768-7

Tabrizi, S. J., Flower, M. D., Ross, C. A., & Wild, E. J. (2020). Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities. Nature Reviews Neurology, 16(10), 529-546. https://doi.org/10.1038/s41582-020-0389-4