Prevalence of Phelan McDermid Syndrome Estimated To Be ~1:7300 Using a Multisource Model.
Tess Levy, David Lapidus, Kate Friedman and 6 others
Phelan McDermid syndrome is far more common than previously thought: the new estimate is 13.7 per 100,000 children, compared with the prior range of 0.25–1 per 100,000.
The US population affected is approximately 17,700, yet fewer than 1,800 are enrolled with the PMS Foundation.
Key findings
1The estimated prevalence of Phelan McDermid syndrome is 13.7 per 100,000 (95% CI 10.02–18.60), substantially higher than the previously cited range of 0.25–1 per 100,000.
2The estimate draws on 179,837 autism cases from 10 data sources, with SHANK3 variant frequencies ranging from 0.089% to 2.475% across cohorts.
3The US prevalent population is approximately 17,700 persons with PMS aged 0–17, while fewer than 1,800 are enrolled with the PMS Foundation, underscoring significant underdiagnosis.
Still to come
How it was doneWhat they foundWhat it means for PTs
Read the rest of this summary
You get three full summaries a month, free, and we do not ask for a card. Search, the TL;DRs and your library stay unlimited either way.
What it does not show
Participation was low: only 5 of 12 laboratories, 1 of 12 clinical centers, and 2 of 19 research centers contributed data, raising the possibility that participating sites are not representative. Over 40 PMS diagnoses at Labcorp were excluded because the test indication field was missing phenotypic information, and one additional laboratory (Quest Diagnostics) could not contribute data at all for the same reason. The assumed 50:50 ratio of deletions to sequence variants rests on a small sample (25 out of 51 cases) and generates the broadest confidence interval among all extrapolation inputs. The entire estimate is anchored to autism-testing cohorts, so PMS cases without an autism indication are captured only through the 38%–40% non-autism adjustment, which itself depends on two prior studies. The method is acknowledged by the authors as difficult to replicate for other rare genetic disorders because of the logistical complexity of collecting comparable data across sites. The estimate is US-specific and relies on CDC autism prevalence figures; it cannot be directly applied to other countries.
Declared interests
The project was funded by CureSHANK and the Seaver Autism Center. D.L. was funded by Neuren Pharmaceuticals. Multiple authors (D.L., M.H., A.K., P.S.) consult for Neuren Pharmaceuticals, and two authors (L.G. and L.S.) are executives at Neuren Pharmaceuticals who may hold stock or stock options. A.K. also consults for PYC Therapeutics and receives research support from Jaguar Gene Therapy; P.S. consults for Jaguar Gene Therapy. T.L. consults for the Phelan McDermid Syndrome Foundation. The paper notes that several clinical trials, including at least one gene therapy, are ongoing for PMS, which is the commercial context for the pharmaceutical involvement.
The easy way to misread this
Do not treat 13.7 per 100,000 as a fixed, directly measured prevalence — it is an extrapolation from autism-testing cohorts that depends on assumptions about assay sensitivity, the deletion-to-variant ratio (based on only 25 of 51 cases), and the share of PMS cases without autism, and the 95% CI spans 10.02 to 18.60 per 100,000. The estimate also reflects US testing patterns and insurance structures and cannot be transferred to other health systems without re-derivation.
Summarised by AI from the full paper, without a clinician reviewing it. Check it against the source before it changes what you do. Read it on PubMed →