Wednesday, October 21, 2009

Calculating HD Risk

A team of researchers from Erasmus University Medical Centre and Leiden University Medical Centre in The Netherlands have discovered a method of calculating an individual’s HD risk without taking any tests, providing genetic counsellors with another valuable tool.

The study found that the majority of people at risk for HD are often afraid to learn more about their genetic status, and their risk of HD may be based on whether the person is a child of an affected individual (50-percent risk) or the grandchild of someone with HD (25-percent risk). Instead, the Netherlands-based project is proposing a better estimation of risk based on factors like current age, length of the CAG repeat in the HD gene in close relatives, information at the age of onset and test results in children. The formula for determining residual risk status (RRS) is provided in a simple spreadsheet format that can be used by genetic counsellors.

Before undergoing a predictive test for HD, the study suggests that individuals may want to learn their residual risk status (RRS) based on their present age and unaffected state. The results can help genetic counsellors better prepare their clients in a pre-test situation or they may influence the decision process, helping an individual decide whether to either proceed with or delay predictive testing.

Before the RRS can be calculated, it must be determined that the individual is asymptomatic for HD, preferably through a neurological exam. Next, the CAG repeat length must be estimated based on the CAG repeat length of the individual’s parent, assuming the HD gene has been inherited. The parent’s age of onset (AO) or a sibling’s AO or CAG can be used if the parent hasn’t been tested. The gender of the affected parent is also important since studies have shown that a gene from the paternal side usually results in a larger CAG repeat length.
The final step is based on the probability that the individual is still symptom-free, given the estimated repeat length. At this point, the RRS can be calculated, though counsellors may also consider any children who have been tested and shown to be gene negative.
Data was drawn from 755 individuals enrolled in the Dutch cohort study, tested between 1993 and 2000, with a CAG repeat length of more than 35. The study’s subjects came from 344 different HD families of which 614 were affected and 141 were asymptomatic gene carriers.
Based on the absence of symptoms and family history, the RSS tool can increase the amount of information that genetic counsellors can offer their clients. The tool is an effective one in helping individuals make a decision surrounding predictive testing – whether to test soon or postpone it for a few years.

A copy of the study can be found at

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