https://www.healthshots.com/brand-stories/biologic-calls-for-better-genetic-testing-at-acmg-2025/
BioLogic Pharma Solutions, in partnership with Neuren Pharmaceuticals, has been on the conference tour this spring to share their research revealing the shortcomings of how diagnostic labs test for SHANK3 variations in Phelan-McDermid syndrome. The Phelan-McDermid Syndrome Foundation has been proudly working with BioLogic on this project. We know that Phelan-McDermid syndrome remains underdiagnosed, but we still do not have a clear picture of how many patients are missed.
Why is Phelan-McDermid Syndrome Underdiagnosed?
There are several different reasons why a rare genetic disorder, like Phelan-McDermid syndrome, is not diagnosed. These often come in two buckets–not getting genetic testing at all versus getting inadequate genetic testing.
Not Getting Genetic Testing
- Difficulty understanding the benefits of genetic testing (the medical provider and/or the family)
- Milder symptom presentation does not lead to genetic testing
- Reduced access to affordable genetic testing
- Diagnostic “overshadowing”, or an autism spectrum disorder diagnosis and/or co-occurring medical conditions (e.g., epilepsy) receives more attention, leading clinicians to overlook an underlying unifying cause
Getting Inadequate Genetic Testing
- Certain testing technology, like chromosomal microarray (CMA), can better detect large deletions in 22q13, but can often miss smaller deletions or SHANK3 sequence variants
- Testing technology is not sensitive enough to identify specific SHANK3 mutations like interstitial deletions or variants
- Many neurodevelopmental disorder or epilepsy genetic panels do not include SHANK3
However, BioLogic’s work in this space is offering a solution to some of these problems.
What is BioLogic Pharma Solution Doing?
Biologic is reviewing diagnostic lab protocols across the United States to identify testing gaps, specifically in Phelan-McDermid syndrome and SHANK3. By comparing which SHANK3 variants each lab is able to detect against all the known disease-causing variants, they are able to pinpoint where diagnostic labs are doing ok and where they could be doing better.
What Did BioLogic Find?
Unfortunately, most diagnostic labs are not doing a great job at testing for SHANK3 variants, which they estimate could be missing up to half of all Phelan-McDermid syndrome patients. In one article, Mary Hames, the CEO of Biological Pharma Solutions, is quoted:
“What we’ve discovered is deeply concerning. Most diagnostic laboratories in the U.S. employ testing protocols that miss critical variants in SHANK3. This isn’t merely an academic concern—it means that labs fail to diagnose patients, delay interventions, and exclude potential participants from clinical trials that could transform their lives.”
So How Does Diagnostic Lab Testing Improve for Phelan-McDermid Syndrome?
BioLogic is offering one important solution: Notifying diagnostic labs of their lab-specific results and identifying how well they are testing for SHANK3 deletions/variants. BioLogic offers important recommendations to improve the testing for the labs that are not doing well. (And they share their appreciation to the labs that are doing well!) In addition, all letters sent to the diagnostic labs include information about the Phelan-McDermid Syndrome Foundation and how, as a patient advocacy group, we can support families who receive a diagnosis of Phelan-McDermid syndrome. In the letters for diagnostic labs, BioLogic recommends that information about PMSF be included in all genetic reports with positive SHANK3 findings.
Our Commitment
Ultimately, we at the Phelan-McDermid Syndrome Foundation are happy to continue our collaboration with BioLogical Pharma Solution, and we hope we can partner with diagnostic labs to help increase awareness and accurate diagnosis of Phelan-McDermid syndrome.
What Can You Do?
- Help spread awareness about Phelan-McDermid syndrome, especially on Phelan-McDermid Syndrome Awareness Day! Making sure more people know about Phelan-McDermid syndrome is a key way to ensure individuals in your community are identified!
- Work with your local medical providers and schools to help educate others about Phelan-McDermid syndrome–if you are interested in doing this, reach out to us!
- Check with your medical provider that they are using the Phelan-McDermid syndrome ICD-10 code in your loved one’s medical records. Check out our previous blog post for more information!
This work was presented at the 2025 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting and at the International Society for Autism Research (INSAR) 2025 Annual Meeting. Our CSO, Dr. Lauren Schmitt, was able to view the poster at INSAR and talk with Brian Eisinger (Medical Science Liaison at BioLogic Pharma Solutions) about next steps!