What Is Phelan-McDermid Syndrome?
Phelan-McDermid Syndrome, often shortened to PMS, is most commonly associated with a deletion or variant affecting SHANK3, a gene important for synapses, the connections brain cells use to communicate. People with PMS can have developmental delay, speech and communication challenges, low muscle tone, autism features, seizures, sleep issues, gastrointestinal concerns, and a wide range of support needs.
Plain-English explanation
Phelan-McDermid Syndrome, often shortened to PMS, is most commonly associated with a deletion or variant affecting SHANK3, a gene important for synapses, the connections brain cells use to communicate. People with PMS can have developmental delay, speech and communication challenges, low muscle tone, autism features, seizures, sleep issues, gastrointestinal concerns, and a wide range of support needs.
Why it matters
PMS is a clear example of why rare disease medicine has to connect genetics, neurology, behavior, development, family experience, and long-term care. Understanding SHANK3 biology may help therapy development, but families also need practical support now: communication, therapies, sleep care, seizure care, school planning, and community.
How it works
Diagnosis usually involves genetic testing that finds a 22q13 deletion or a pathogenic variant involving SHANK3. The size and location of a deletion can vary, and symptoms can vary widely. Research is exploring gene replacement, pathway biology, model systems, outcome measures, and clinical trial readiness, but care today remains multidisciplinary and individualized.
Key terms
Related interviews and articles
Dr. Guoping Feng (MIT) on SHANK3 Gene Therapy, Brain Disorders, and What’s Coming Next
Dr. Guoping Feng
Welcome — I’m Ron Kleiman, and this is GENEration Hope. In this episode, I’m joined by Dr. Guoping Feng, Professor of Neuroscience at MIT, affiliated with the McGovern Institute, the Yang Tan Collective, and the Broad Institute. 
Dr. Katy Phelan: The Origins of Phelan-McDermid Syndrome + Why Hope Is Growing
Dr. Katy Phelan
Welcome to GENEration Hope — I’m Ron Kleiman. Today’s guest is Dr. Katy Phelan, a pioneering human geneticist and one of the founders of the Phelan-McDermid Syndrome Foundation (PMSF). This conversation was recorded at the PMSF Annual Co...
Dr. Alex Kolevzon on Gene Therapy, SHANK3 & the Future of Treatment
Dr. Alexander Kolevzon
Welcome to Generation Hope. In this wide-ranging interview, Dr. Alex Kolevzon (Mount Sinai) sits down with Ron to discuss the science, the trials, and the human side of gene therapy for rare neurodevelopmental disorders. In this episode...