Neurológia pre prax 2/2023

Genetic factors influencing age of onset of Huntington’s disease and markers of its prediction

Huntington‘s disease is an autosomal dominant neurodegenerative disorder with progressive motor, cognitive and behavioural impairment. The disease is caused by a mutation in the HTT gene, which results in an abnormal expansion of CAG repeats. Although the usual age of clinical onset of the disease is around 40 years, its range extends from childhood to the eighth decade. The main factor influencing this variability is the number of repeats of the expanded allele, on which the age of onset of the disease is inversely dependent, especially between 55 and 80 repeats, but genetic modifiers identified mainly in genome-wide association studies also play an important role. The onset of the clinical manifestation of the disease can be predicted to some extent by quantifiable neuropathological changes, some of which may precede it by up to more than two decades. In addition to the implications for the patient, prediction of this value is important for research and development of new treatments.

Keywords: Huntington’s disease, CAG triplet, age of onset, genetic modifiers