Explainer · Brain & Mental Health
Phelan-McDermid syndrome may affect about 1 in 7,300 people, far more than earlier estimates
Phelan-McDermid syndrome is a genetic condition that causes developmental delay and often autism. Pooling genetic test results from 10 sources, researchers estimate it is many times more common than thought.
- Researchers pooled genetic test results from 179,837 autistic people across 10 labs, research and clinical centers.
- Between 1% and about 2.5% of those tested had Phelan-McDermid syndrome.
- Adjusting for testing methods and other factors, they estimate about 13.7 per 100,000 people, or 1 in 7,300.
- Earlier estimates ranged from 2.5 to 10 per million births.
- The estimate rests on several assumptions and on autism rates that vary over time.
Phelan-McDermid syndrome is a genetic condition that few people have heard of. It causes developmental delay, limited or absent speech and, in many cases, autism. Families often wait years for a diagnosis, and it has long been described as rare.
A study in Autism Research, led by researchers at the Icahn School of Medicine at Mount Sinai in New York, suggests it may be much less rare than thought. Their estimate is about 1 in every 7,300 people.
What Phelan-McDermid syndrome is
MedlinePlus Genetics explains that 22q13.3 deletion syndrome, which is also commonly known as Phelan-McDermid syndrome, is usually caused by a missing piece near the end of chromosome 22. That piece includes a gene called SHANK3.
SHANK3 makes a protein that helps connections between nerve cells work. A lack of it is thought to contribute to the developmental delay, intellectual disability, and absent or severely delayed speech typical of the condition. Some people have a change in the SHANK3 gene itself rather than a missing piece of chromosome.
How the Phelan-McDermid estimate was built
Counting a rare genetic condition is hard, because many people are never tested. The team asked genetic testing labs, research centers and clinics how many of the autistic people they had tested turned out to have Phelan-McDermid syndrome.
Ten sources participated and data from 179,837 autism cases were evaluated. The researchers then adjusted for how sensitive each test was, for people with the syndrome who do not have autism, and for other factors, and used US autism rates to scale up to the whole population.
What the Phelan-McDermid numbers showed
Among autistic people who were tested, between 1% and about 2.5% had the syndrome, depending on the source. The raw figures differed partly because the labs used different tests.
After all the adjustments, the final weighted average was 13.7 per 100,000, or about 1 in 7,300 people. The authors note that previous estimates vary from 2.5-10 per million births, so the new figure is many times higher.
Why a higher Phelan-McDermid count matters
How common a condition seems shapes how much attention it gets. The authors write that the true prevalence of genetic disorders is critical for understanding disease burden, planning testing and care, and judging the value of new treatments.
If the estimate holds, many people with Phelan-McDermid syndrome have not been diagnosed. A diagnosis can help families find specialist care, connect with others, and join research or trials. One of the authors lists an affiliation with a drug company, Neuren Pharmaceuticals, alongside academic affiliations.
What the Phelan-McDermid model cannot settle
The estimate stacks several steps and assumptions, and each adds uncertainty. It depends on US autism rates, which have changed over time, and on assumptions about how many people with the syndrome are not autistic.
The authors note that parts of the SHANK3 gene are hard for standard sequencing to read, and that another method based on mutation rates gives a lower figure of about 5 per 100,000. Sources that took part may also differ from those that did not.
What this changes for Phelan-McDermid testing
For families of autistic children, or children with developmental delay and speech problems, the study adds weight to the value of genetic testing. Testing that includes both chromosome analysis and gene sequencing is more likely to pick up the syndrome.
Families with questions can ask their doctor or a genetic counselor whether testing is appropriate, and what a result would mean for care.
People also ask
What did the study find?
Across 10 sources and 179,837 autism cases, the frequency of Phelan-McDermid syndrome diagnoses ranged from 1% to about 2.5%. After adjustments, the final weighted average was 13.7 per 100,000 (95% CI 10.02 to 18.60 per 100,000), or about 1 in 7,300 people in the general population.
What is Phelan-McDermid syndrome?
A genetic condition, also called 22q13.3 deletion syndrome, caused by a missing piece at the end of chromosome 22 or a change in the SHANK3 gene. It typically causes developmental delay, intellectual disability and absent or severely delayed speech, and often autism.
What does the SHANK3 gene do?
It makes a protein that supports synapses, the connections between nerve cells in the brain. Having only one working copy reduces the protein and is thought to cause many features of the syndrome.
Why do prevalence estimates matter?
They shape how much testing, care and research a condition receives, and whether treatments in development are judged worthwhile. An undercounted condition can be overlooked.
Why might earlier estimates have been lower?
Older genetic tests missed many cases, especially small changes in SHANK3, and not everyone with autism or developmental delay is tested.
Should an autistic child be tested for it?
Genetic testing is recommended for many children with autism or developmental delay. Families can ask a doctor or genetic counselor whether testing is appropriate. This is general information rather than medical advice.