Kate highlights Dr. Sid Srivastava, a clinician at Boston Children's Hospital studying Phelan-McDermid syndrome in the Natural History Study. She asks - how did he become interested in rare diseases like Phelan-McDermid syndrome? What does a typical Natural History Study visit look like for families? What research projects is he working on? What are the biggest findings he's seen in studying the syndrome? For enrollment information on the Natural History Study, see: https://pmsf.org/enrollment-is-currently-open-for-phase-ii-of-the-phelan-mcdermid-syndrome-pms-natural-history-study/

Dr. Conny van Ravenswaaij runs an expert Phelan-McDermid syndrome clinic in the Netherlands, and was a leading force behind the European Phelan-McDermid syndrome clinical consensus guidelines. She and Kate discuss the clinical recommendations and how to share them with your clinicians. Conny also covers a clinical trial that she ran on intranasal insulin, and current work studying Ring 22 in Phelan-McDermid syndrome. 

Important links:

Clinical synopsis of european guidelines: https://ern-ithaca.eu/wp-content/uploads/2023/05/Clinical-synopsis-PMS-1.pdf

PMSF conference session on genetics (including Ring 22): https://www.youtube.com/watch?v=EOmPYpim3_8

Kate chats with Jaguar Gene Therapy about the progress the company has made in testing a gene therapy for Phelan-McDermid syndrome over the past couple of years. She asks what steps are still needed to take this therapy to clinical trials (if it proves safe and effective). Also covered: how gene therapy works, the target as SHANK3, ongoing animal testing, and timelines.

Recently, the Phelan-McDermid Syndrome Foundation was successful in applying for and receiving a specific ICD code (International Classification of Diseases code) for Phelan-McDermid syndrome from the Centers for Disease Control (CDC). Kate sits down with Annie Kennedy of the EveryLife Foundation, who has longstanding expertise in what a specific code can mean for progress for rare diseases. Kate asks - what exactly is an ICD code? What does this mean for progress in Phelan-McDermid syndrome research? Why didn't we have one already? Can it be used internationally? What was the process in getting one? What are some examples of progress after getting a code? What is the code not helpful for?

Annie Kennedy is the Chief of Policy, Advocacy, and Patient Engagement at the EveryLife Foundation. She also previously served within the Parent Project Muscular Dystrophy and the Muscular Dystrophy Association. Her work includes building strong partnerships with policy makers, federal agencies, industry partners, and alliances to advance research and access in rare disease. She has developed an ICD code roadmap with the EveryLife Foundation, has conducted economic burden studies in rare disease, led efforts for newborn screening, led access efforts after the first therapies were approved by the FDA for Duchenne muscular dystrophy, and much more.

Dr. Kohlenberg and Dr. Rahman are both clinicians with expertise in neuropsychiatric illness in Phelan-McDermid syndrome. They discuss the first signs and symptoms, where to find treatment guidelines, how to connect your clinician with experts, and the difference between neuropsychiatric illness and regression. They discuss top research questions and progress. Kate points out where families can find key resources along the way.

Dr. Kohlenberg is a pediatrician with decades of experience in child psychiatry. She is also mom to an adult daughter with PMS who was diagnosed as a result of neuropsychiatric illness, and Tesi has done a lot of work to understand how to best manage this for her daughter and many other people with PMS. She played a leadership role in starting the Neuropsych Consult Group, and is on PMSF's Medical Advisory Committee.

Dr. Asif Rahman is a psychiatrist and is currently a fellow in Child and Adolescent Psychiatry on the Research Track at Mount Sinai. He is being funded by PMSF to do more research into neuropsychiatric illness in partnership with the Natural History Study and is being mentored by Dr. Alex Kolevzon.

Gabi Conecker leads the Inchstone Project, an effort to ensure people with conditions like PMS don't bottom out on clinical assessments and their progress is measured. For clinical trials, it is crucial to show a drug is making positive change, which requires sensitive assessments. PMSF is taking an active role in the Inchstone Project, and other projects to improve clinical assessments. Clinicians in PMS and other groups are also constantly working towards improved clinical assessments. This podcast discusses some of what it takes to improve assessments.

Gabi Conecker is the Founder of Decoding Developmental Epilepsies, previously "Wishes for Elliott," named after her son with SCN8A epilepsy, alongside her mother JayEtta. She is also a leader of DEE-P connections which provides resources to people with rare severe epilepsies.

PYC Therapeutics is a pharmaceutical company developing an RNA therapeutic for Phelan-McDermid syndrome. Dr. Sue Fletcher (Chief Scientific Officer) and Rebecca Simmons (current Group Lead) describe these efforts. Kate asks what exactly are RNA therapeutics? What is this drug targeting and how does it work? What are the timelines and plans going forward? What will be measured to see if the drug is working? What types of challenges are associated with the approach? What can the foundation and families do to support drug development?

Dr. Billy Bennett has been working with the Foundation for the past year on two initiatives that are considered family engagement research. The first is focused on the genetic counseling process and some of the common challenges families face in these meetings. We review a federally-funded research project that collected feedback from families to improve the genetic counseling process, and cover the next steps we are taking to change this process alongside genetic counselors. We also review the findings from a second initiative, called CANDID, an NIH-funded conference.  CANDID served to bring together families, clinicians, scientists, patient advocacy groups, and industry partners to consider how to better detect and treat GI disorders in people with PMS, autism, and other neurodevelopmental disorders. In this episode, we review the takeaways from CANDID and discuss the many steps that are occurring afterwards to advance research in this area.  

Dr. Billy Bennett is a pediatric gastroenterologist, and a clinical researcher at Indiana University. He is on both the medical and scientific advisory committees at PMSF. He is also a PMS dad to his daughter Cecilia, who is the inspiration for this work.

Dr. Kolevzon has been leading a team of clinicians to develop clinical guidelines for the management and monitoring of PMS.  Kate asks - what are clinical consensus guidelines exactly? Which categories of medical care will be included? When will the guidelines be released? How can families best use this information? How are guidelines developed? How have the guidelines changed since the first iteration in 2014? What areas of research have seen the most growth? How can families bring forward patterns they notice to help shape the guidelines as they continue to evolve?

Dr. Alex Kolevzon is a psychiatrist and professor at the Icahn School of Medicine at Mount Sinai. He is a long-standing expert in Phelan-McDermid syndrome research as a leader of the PMS Neuropsychiatric Consult Group, the PMS Natural History Study, the PMSF medical advisory committee, and he sees many people with PMS in the clinic. 

In this episode, we welcome Dr. Natasha Ludwig (Kennedy Krieger Institute / Johns Hopkins) and Dr. Jenny Downs (Kids Research Institute, Australia) for an exciting update on the Inchstone Project. The Inchstone Project is a cross-syndrome collaborative international effort to improve how we measure progress and quality of life for individuals with individuals with developmental and epileptic encephalopathies (DEEs), including Phelan-McDermid syndrome (PMS).

We discuss:

• What the Inchstone Project is and why it matters

• How families helped shape new research by contributing to the DEE Parent Speak Survey

• Key findings on quality of life, including the importance of communication, cognitive skills, and touchscreen use

• What “clinical meaningfulness” really means—and why small changes can have a big impact

• How this research is informing clinical trial readiness and future interventions

• What’s next for the Inchstone team, including new measures of awareness and a follow-up longitudinal study

PMS families made up nearly 20% of the study sample! This is such a powerful reminder that your participation is helping to change the research landscape.

Tune in to learn how every inchstone of progress matters—and how you’re helping move science forward.

Recorded: 7/22/2025

Initially Aired: 1/21/2025

Updates since the recording:

• Dr. Ludwig is a confirmed speaker at our 2026 PMSF Family Conference in Aurora, CO!
• Dr. Ludwig's paper on caregiver-reported quality of life in individuals with DEEs has been published! You can read the full text here: https://pmc.ncbi.nlm.nih.gov/articles/PMC12804316/