This story in the Wall Street Journal about genetic testing shows the speed of changes in the medical community’s understanding of how and whether certain genes cause hereditary disease.
The article quoted Dr. Jodie Ingles, a geneticist from the University of Sydney in Australia who specializes in HCM and has published a recent article on the subject. Dr. Ingles said that 22 out of 33 genes comprising a genetic testing panel commonly used to test for HCM had either limited or no evidence of being disease causative.
These false positives are dangerous, according to Dr. Ingles, because invasive treatment decisions, such as implantable defibrillator (ICD) placement, may be based on this erroneous genetic information.
Though they can be lifesaving if appropriate, ICDs also have potential to cause harm to the patient. ICDs may cause infection, may inappropriately discharge, or they can be subject to lead complications which may necessitate additional surgeries.
You can read more about Dr. Ingles’ research and study results here.
A recent editorial published in Circulation: Genomic and Precision Medicine suggests that current HCM screening protocols may need adjustment to account for recent findings by a study by researchers in the Netherlands. The Dutch study, published in the same journal, found that of 620 relatives of HCM patients who underwent genetic testing, 43% were found to be genetically positive for HCM, while 30% were diagnosed with HCM at the initial screening. 16% more went on to develop HCM during 7 years of repeated cardiac evaluation.
On the other hand, the 57% of relatives found to be genotype-negative were released from clinical HCM follow-up.
The Australian authors of the editorial, Semsarian and Ingles, note that current screening protocols would have failed to identify the 6 children (15%) who were diagnosed under the age of 12, half of which had a particularly malignant family history.
Additionally, few teens were diagnosed with HCM, which stands in contrast to current opinion that HCM is most likely to develop during adolescence. Indeed, most newly diagnosed family members were older than the age of 36, with 44% being over the age of 50.
Lastly, Semsarian and Ingles note their concern with general utilization of the Dutch practice of releasing a gene negative family member from serial follow up since the impact of all genes which have a role in causing HCM is not yet known while new genes which may cause HCM are still being identified.
Semsarian and Ingles also note that the Dutch patient sample differs from more typical patient populations found in the U.S. and Australia where causes of HCM are more diverse and cannot be easily tied to a specific gene.