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  1. D A Mackey
  1. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia

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    Two clinical ophthalmic geneticists, who also have extensive laboratory experience, have provided opinions on the problems of predictive DNA testing in an ophthalmic setting of ADRP. The rapid progress of genetic research associated with the human genome project has raised many new ethical issues and made clinicians reconsider conventional treatment issues. Many ethical guidelines are being imposed on researchers and clinicians that will need to be modified in the future to reflect the changing perspective of the current clinical practice and in accordance with patient’s wishes.

    How will it change management? Predictive DNA testing for an untreatable disease

    A well informed adult can consent to a predictive DNA test. However, predictive DNA testing in children raises issues of what the child (as the person now and the adult he/she will become) would want. To only order an investigation that will change management is an important axiom of clinical care, not just for hospital financial administrators. Some would argue that there is no value in early diagnosis of RP as it will not change management. This applies to the electrophysiology testing as much as the DNA testing. It is also important to consider the specificity and sensitivity of the ERG and the DNA test. The arguments for DNA testing if there was no other treatment and no risk of using a night light would be poor. However, there is a slight chance that treatment for nyctalopia with a night light may not be totally safe. This is a controversial area. Most studies conducted since the original paper proposing that night lights cause myopia have failed to support this finding.1 If the parents were insistent despite counselling, then the night light argument could be used to convince an ethics committee. Managing the RP is probably more important than managing myopia.

    How will it change management? Predictive DNA testing for a treatable disease

    Few people would argue against predictive DNA testing for a treatable disease such as retinoblastoma, where a negative DNA test can spare a child from 10 examinations under anaesthesia.2 Similarly in glaucoma (myocilin related) DNA testing allows early diagnosis and treatment to prevent glaucoma blindness.3 However, the timing of such testing would be an issue if the disease did not need to be treated until adulthood anyway. When will predictive DNA testing for RP be of value? How far away are treatments? The only tested preventive treatment for RP is high dose vitamin A.4 This in itself would be a topic for this series in the BJO. What if only some genetic subgroups of RP were responsive to high dose vitamin A5 (such as in the case of Sorby’s fundus dystrophy6). Who would pay and organise the massive amount of DNA testing to work out which genetic subgroup of RP each patient belonged to and how long it would take to screen everyone with RP? Research groups do not have the resources for this and may not still be set up to do testing on a gene that was studied over a decade ago. If the family knows which gene mutation they have then they may be proactive in seeking out new treatments. Few RP clinics would be able to contact all their patients if new treatments did become available. It is possible in this case scenario that the family could have their gene mutation identified now and the girl could be tested at a later date if deemed appropriate.

    There is surprisingly little information on the sensitivity and specificity of the ERG, when one considers that this test has been in use for decades. The evaluation of the sensitivity and specificity of DNA testing is only in its very early stages. This will be an important area of future research. The worst case scenarios would be to tell someone they would get a severe disease when they will never be affected even though they carry a presumed mutation or to tell someone that they would not be affected when they do develop the condition.

    Genetic information resources

    Useful information is available on “Understanding gene testing” by the US Departments of Health and Human Services (

    Retina and retinitis pigmentosa organisations also have useful web pages. With the rapid changes in genetics it is useful to keep up to date with online resources. Lists of RP genes are available from Retnet ( and OMIM ( Proving that a particular gene is pathogenic is a more complex problem. Although many mutations are cited in the literature, many of these have been single case reports. It is likely that some of these will be polymorphisms rather than disease-causing mutations. Thus, incorrect predictive data could be given to a patient who is carrying a polymorphism.

    If RP gene testing is requested by the family then the clinician should contact his/her local laboratory and genetics unit that may already have arrangements with a DNA testing laboratory. Contacting various research institutions around the world may identify a laboratory willing to do the DNA testing. An online listing of laboratories doing research or diagnostic testing is available from the University of Washington and Children’s Health System, Seattle ( However, as the research phase of identifying RP DNA mutations is almost over, very few laboratories will offer this service free of charge. Families who were involved in earlier research studies now have access to the mutation present in their family and thus a cost effective test for other family members would be possible. For families who did not participate in earlier research, this is not possible without considerable expense.

    Where are my results?

    Many patients expect DNA results to be returned with the speed of a routine blood count. We must all give patients realistic time lines for preliminary and final results from DNA testing. Hopefully health funding bodies will see the benefit of funding DNA screening in an efficient manner. This may involve targeting common mutations in specific populations. Although we may be unable to provide 100% mutation screening, it may be efficient to just look for common mutations. In addition, there will be better information on the phenotype-genotype correlations of these as well as information on penetrance, age of onset, and expected visual outcome. Screening large families may cause problems with some members not wishing to participate and privacy concerns will need to be addressed.

    Considering the child’s wishes

    If parents do have their children tested for genetic diseases, this is like many choices that parents make on behalf of their children. There is no right or wrong answer, but parents need to be made aware of issues and the possibility that the child may later wish to have had a different choice. One needs to look at the issue in a similar light to the disclosure of adoption to adopted children, where cultural norms have changed over the years. It may be better to inform children when they are younger than to have a genetic test result come as an agonising decision in later life. Does our current idea of forcing people to make choices all the time actually cause more harm than the century old method of letting the doctor decide? It may be less harmful to let a 4 year old know that she won’t join the airforce than telling a 19 year old with her heart set on it. It is important to consider the time and place as well as the social and cultural setting of each family. The approach used for one may not be the same for another.

    When parents have an ill child they would like everything possible to be done for their child. If no treatment is available then participating in research can be therapeutic for the family (just as setting up a charity or fund raising can be). It is important that we never take away hope from families with hereditary eye diseases by saying we can do nothing.


    Genetic testing is just another enabling part of clinical medicine that should be funded as such. Although specific guidelines are imposed on genetic testing these should be the same for any clinical test “Will it change management?” and “What would the patient want?”


    This was supported by the Eye Ear Nose Throat Research Institute.

    We would like to thank Lori Bonertz, Robert Buttery, Jamie Craig, Chris Inglehearn, Danielle Healey, and Lisa Kearns for their helpful comments on the manuscript.


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