At the annual meeting for the Association for Molecular Pathology this past November, Joseph Maleszewski, M.D., a cardiovascular pathologist and Professor of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, Minnesota, presented about phenotypes and genotypes in the understanding and diagnosis of cardiovascular disease.
Traditional techniques have paved the way to targeted molecular testing and individualized medicine in cardiovascular disease. According to Dr. Maleszewski, who spoke with CAP Today, “Specifically with regard to cardiovascular disease, there is a growing recognition that neither traditional phenotypic nor genotypic information in isolation is particularly useful in terms of understanding the entire clinical picture. We have become increasingly aware that both clinical and pathological phenotype as well as genotype need to be married up to make informed decisions about patients and family members.”
To understand the causes of sudden death, Dr. Maleszewski and colleagues have been examining autopsy reports in a group of college athletes who died suddenly. “Unfortunately,” Dr. Maleszewski says, “many of these cases are difficult to adjudicate because of the varied ways in which these cases are approached across the country. Resources for evaluating sudden death are certainly different from jurisdiction to jurisdiction.”
To Dr. Maleszewski, these observations support the need for widespread access to combined pathologic and genetic analysis. “It is important to start taking a closer look at cases where there is no clear finding at autopsy,” he says. For those cases, “we are advising that they seek out a subspecialist consult to look for subtle findings that may direct where to look in the genes for culprit lesions. Having genetic tests available makes a better pathologic exam more useful.”
In the article, Dr. Maleszewski also described a recent case that highlights the importance of specialist-guided postmortem genetic testing. An apparently healthy teenage athlete died suddenly in her home. The histologic findings were subtle, but also suspicious, raising concerns she might have had hypertrophic cardiomyopathy, and genetic testing corroborated the suspicion.
“The most important genetic result was that the test was positive for a mutation known to be associated with that condition. We used that information to screen the decedent’s relatives, thereby ruling about half of them out of further testing and intervention and focusing screening on those at highest risk. In the old algorithm, we would have done ongoing rigorous physical exams of all surviving family members until they manifested disease. Given the subtle nature of this phenotype, it is conceivable that the disease may not have been picked up as early in some of this girl's family members without the positive genetics," Dr. Maleszewski said.