Perhaps 70- 85% of rare diseases have a root in genetics, – which is why continuous research and reporting is so critical for those with rare conditions. This is exactly why Patient Worthy helps provide media coverage for the American College of Medical Genetics conference each year. Two thirds of rare patients are children. Each year as more advances are made, approximately 250 new conditions are discovered. We find that conditions which we called one thing, such as” epilepsy,” are actually many different conditions that have seizures as a salient characteristic, but different, usually genetic, reasons causing the seizures. Discovery of the cause of the seizures provides an opening for gene therapy or other therapeutic measures.
The American College of Medical Genetics conference helps clinicians keep up to date on the latest discoveries as well as the latest diagnostic tools. Still, there is much we still do not know. In the area of central nervous system disorders, still today, only 35% have a definitive diagnosis.
One take away for me this year was to see in this age of AI, Whole Genome, Whole Exome Sequencing, and scans of many types, that experience and examination of the phenotype is still critical in diagnoses. The phenotype is the observable characteristics of a person, from hair swirls, ear placement, to the symmetry or asymmetry of their facial features and their overall physical form. For this reason, photographs and videos are a critical part of the data used for analysis. An open database of cases and faces called the GestaltMatcher, now has more than 10,000 cases to help identify rare syndromes. FaceMatch.org, an Australia based organization has similar aims.
One of the latest diagnostic tools and the subject of several sessions was “long read” sequencing. In this form of genetic sequencing, longer sections of genetic material are examined, and this has proved superior for detecting rare splicing events.
PacBio, Oxford Nanopore, and Illumina are all able to do long read sequencing now and when compared on the same set of diverse samples they all had some strengths.
In this vein the cost of sequencing has gone down, while the speed has gone up. Look at the chart below:
Both Rady’s Children’s hospital and Standford University Hospital can have results from Whole Genome sequencing in 6-14 hours. This is especially helpful for critically ill newborns. Learn more about high-speed sequencing in this article.
One session discussed breaking the news to the parents of newborns when the results of rapid genetic testing revealed a devastating condition, incompatible with life. Several genetic counselors said that parents were still grateful for the testing as it made it possible for them to choose comfort care for their children rather than painful interventions that would not help.
One of my favorite sessions each year is the diagnostic dilemma session, when geneticists present cases that they have been unable to solve. Then a room of 750- to a 1000 physicians, genetic counselors and researchers have an opportunity to think about the case and suggest routes of further testing and a possible diagnosis. Because some rare diseases are so very rare, they may not be seen in a lifetime of practice. However, by putting the experience of so many together, some ultra rare cases have been diagnosed, with several geneticists in their 90’s contributing. There is a nationwide shortage of geneticists and fewer and fewer physicians are choosing this long and complex specialty that is seldom as financially rewarding as other specialties which have similar lengths of training. It is critical that we find incentives to increase both the number of physicians and the number of fellowships in this field.