23 April 2018

Gene tests – what you need to know

Clinical Evidence Based Genetics

Alzheimer’s disease, diabetes and mental health genetic tests have all been singled out as areas to be wary of in the long-awaited Genomics in General Practice handbook from the RACGP. 

The handbook has been in the works for years and is the first major piece of guidance for general practitioners since a 2007 resource by the now defunct Biotechnology Australia. 

As the cost of genetic and genomic testing has become more affordable, and private companies are advertising directly to consumers with often exaggerated claims of benefits, the experts behind the handbook were conscious to highlight tests for conditions such as Alzheimer’s and mental illness which patients most commonly expressed interest and wanted to discuss with their GP. 

Tests for pharmacogenomics and MTHFR were other areas of concern, with the authors advising doctors there was little if any evidence to support their usefulness in routine clinical practice. 

“While many of the drugs commonly prescribed in general practice (e.g. warfarin, fluoxetine) are influenced by genetic variation, there is currently no clear recommendation in Australia about the use of pharmacogenomic testing,” the authors said.

Interest in MTHFR testing was another area currently “blowing out” in genomics, with alternative practitioners ordering tests for a range of chronic illnesses, explained author Professor Sylvia Metcalfe, honorary fellow with Murdoch Children’s Research Institute. 

These kinds of spurious tests were behind a growing number of people taking folate or vitamin B12 supplementation unnecessarily, she added.  

The guide offers a cautious approach and outlines the potential ethical and practical advice GPs can give their patients, which includes warnings over potential privacy and credibility concerns, as well as implications for health and life insurance. 

While the guide authors have taken a fairly conservative approach, it was one GPs were likely to support, Professor Metcalfe, also an honorary professor in paediatrics at the University of Melbourne, said.

“We’ve been quite clear that although a lot of things are advertised in a very strong way, much of that testing is not predictively useful.”

The booklet was designed to be easy to navigate and includes a short few practice points at the beginning of each condition’s chapter to summarise the current knowledge. 

For example, the section on autism spectrum disorder explains that referral to a paediatrician, will usually include a genetics evaluation of the child providing a specific diagnosis in 30 to 40% of cases. 

It adds that GPs “can order a chromosome microarray (CMA) at the point of referral to a paediatrician in order to speed up this process”.

The booklet highlights when to order tests, when not to, and when to refer on to specialists and genetic counsellors. 

The sections on familial cancer and prenatal testing are very clear about the value of testing in these situations.

 Professor Metcalfe said she hoped GPs would familiarise themselves with the indications for reproductive carrier testing and other reproductive genomic testing.

The guide includes information on how to take a thorough family history and draw a family history pedigree. 

Women and their partners planning a pregnancy, or who are already pregnant, should have a comprehensive family history recorded. Known carriers or parents-to-be with a family history of a genetic condition should be made aware of and offered testing and referral to specialist services, it says.  

The guide also provides rebuttals to some commonly held myths in the community, such as the idea that having a gene for a disease means that the patient will inevitably develop the disease. 

“If the gene variant shows variable penetrance (i.e. penetrance less than 100%), the risk of disease can be uncertain.”

Other conditions discussed in the new guide include autism spectrum disorder, cystic fibrosis, developmental delay and intellectual disability, fragile X syndrome and associated conditions, familial hypercholesterolaemia, haemoglobinopathies, hereditary haemochromatosis, hereditary thrombophilia, melanoma, neurofibromatosis type 1, sudden arrhythmic death syndrome, chromosome microarray and newborn screening.

The Genomics in General Practice guide can be found on the RACGP website.