F15 Is there a correlation between age of onset of symptoms and number of cag repeats in patients with juvenile and younger onset huntington’s disease? a study of 27 patients in the north east of england

Abstract

Background Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder characterised by involuntary movements, psychiatric symptoms and cognitive deficits. It is caused by the expansion of a CAG triplet repeat on chromosome 4p16.3, which produces an expanded polyglutamine repeat in the huntingtin protein. Number of repeat expansions have been shown in multiple studies to be inversely correlated with age on onset of symptomology in patients suffering from adult onset HD. There is less evidence available regarding correlation between repeat size and age of onset in juvenile and younger onset HD; these patients typically have CAG repeat sizes of at least 50. Aims To determine a correlation between CAG repeat size and age of onset in Huntington’s Disease patients in the North East of England with more than 50 CAG repeats. Methods/techniques Patients seen in clinic over the last six years with more than 50 repeats on genetic testing were identified (n=27). Number of CAG repeats on genetic testing were identified. Notes of patients were reviewed to determine age of onset of symptoms. Pearson Product Moment Correlation was calculated and p values determined for the correlation calculations. Results/outcome 27 patients were identified, with repeat sizes varying between 51 and 173 and ages varying between 2 and 30. A negative correlation of −0.78 (p=0.0000015) was found between age of symptom onset and repeat size. There was one significant outlier, a young girl with 173 repeats and symptom onset at the age of two years. When this patient was removed from analysis, negative correlation between age of symptom onset remained significant at −0.73 (p=0.000018). In our sample 21 patients showed the age of onset of the symptoms of HD about 18 years of age despite them having 50 + CAG repeats. Conclusions Our results support the results from previous studies that CAG repeat size is negatively correlated with age of onset of Huntington’s Disease symptomology, and that this finding is demonstrable in the patient group with over 50 CAG repeats. Our results also indicate that carrying 50+CAG repeats may not directly influence the age of onset (before 18 years) under the current diagnostic criteria of Juvenile onset HD.