Onset Of Huntington’s Disease May Occur In Childhood

Huntington's disease is caused by a single gene mutation. Image: nobeastsofierce/Shutterstock.com

Huntington’s disease is a devastating genetic condition that typically manifests in adults between the ages of 30 and 50, with most sufferers surviving for 10 to 20 years following the onset of symptoms. However, a new study in the Journal of Huntington’s Disease provides evidence that the gene responsible for the condition may in fact disrupt brain development throughout a carrier’s life, with these deleterious effects beginning in childhood.

Caused by a mutation to the huntingtin (HTT) gene, Huntington’s disease is a neurodegenerative illness that is characterized by neuronal damage within certain brain regions. Until now, it had generally been assumed that only adult brain cells are affected by the mutant HTT variant (mHTT), which exerts its toxic effects over a period of many years.

Yet the latest findings hint towards an alternative pathway for the development of the disease by indicating that mHTT actually disrupts the growth of brain cells in children, increasing their susceptibility to neurodegeneration once they reach adulthood.

The researchers have published two separate papers, the first of which pulls together all of the existing evidence for their theory. In this review study, the authors present their case by explaining that the HTT gene is vital for brain development and that any alterations to its function would likely disrupt the formation of neuronal pathways in children.

Using results from a brain imaging study of a group of children with a family history of Huntington’s disease, the study authors point out that some children as young as six displayed altered development in a brain region called the striatum. However, at this age the brain appears capable of compensating for this damage, which is why no symptoms are evident.

According to the authors, these damaged neurons remain in a “mutant ready state” throughout adolescence and begin to cause symptoms later in life as years of stress chip away at the brain’s capacity to compensate for these deficient components.

This illustration highlights the differences between the classical theory regarding the development of Huntington's disease and the new theory being suggested by the study authors. Image: Journal of Huntington's Disease

In a second study, the same researchers sought to determine if mHTT alters the physical development of these children. Genetic tests were carried out on 186 individuals between the ages of 6 and 18, all of whom were identified as being at risk for Huntington’s disease, in order to determine those that carried the mHTT variant.

After analyzing participants’ body mass index (BMI), the study authors noted that mHTT carriers tend to display a lower BMI than non-carriers from the age of about 15 onwards. In the case of boys, the mutant gene is associated with increased height yet no corresponding increase in weight, leading to a reduced BMI, while girls that carry mHTT tend simply to weigh less than those that don’t, with no noticeable difference in height between the two groups.

It’s not yet possible to say exactly why this is the case, but it may have something to do with the role that the HTT gene plays in energy metabolism. Regardless, these findings strongly indicate that the mutated variant affects the development of children, suggesting that certain physical and neurological changes associated with Huntington’s disease may occur up to 30 years before the onset of acute symptoms.

With gene therapies currently being developed, study author Peg Nopoulos explained in a statement that research like this is likely to play a vital role in the treatment of the condition. “Gene therapy trials are finally here. However, interfering with a gene responsible for brain development early in life must be done with an abundance of caution,” she said.

“Understanding how mHTT affects brain development is vital in the context of planning disease prevention therapies.”


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