Scientists at the Seaver Autism Center for Research and Treatment at Mount Sinai have found that a genetic disorder closely tied to autism may be far more widespread than previously believed. Thousands of cases may still be undiagnosed. The research suggests that Phelan-McDermid syndrome (PMS) affects an estimated one in approximately 7,300 people, with the figure 1 standing for the frequency of affected individuals.
A rare genetic disorder known as Phelan-McDermid syndrome develops when there is a deletion or mutation involving the SHANK3 gene on chromosome 22. The condition brings with it a wide variety of medical, intellectual, and behavioral difficulties. The vast majority of affected individuals also fit the diagnostic criteria for autism spectrum disorder, and changes affecting SHANK3 are estimated to make up as much as one percent of autism spectrum disorder cases.
A study in Autism Research puts the rate of the condition at about 13.7 cases in every 100,000 people, or roughly 1 out of every 7,300 individuals. The numbers translate to more than 45,000 people in the United States. Researchers say many cases may go unrecorded because genetic testing is frequently skipped, even as specific treatments are moving toward clinical trials.
The SHANK3 Gene
The SHANK3 gene sits on chromosome 22, and deletions or mutations there bring about Phelan-McDermid syndrome. Alterations involving this gene are considered responsible for around one percent of all cases of autism spectrum disorder.
This condition is linked to a wide variety of physical, mental, and conduct issues. The majority of individuals affected by it also meet the diagnostic requirements for autism spectrum disorder.
Autism spectrum disorder is associated with the condition, yet not every person with Phelan-McDermid syndrome fits the criteria for autism. The estimate takes into account undiagnosed cases, genetic testing limitations, and individuals with Phelan-McDermid syndrome who do not meet the criteria for autism.
How the Researchers Got Their Numbers
The Mount Sinai team worked with genetic testing laboratories, academic medical centers, and autism research programs to estimate the prevalence of the condition. They examined data from nearly 180,000 people with autism who had undergone genetic testing.
The study pulled together data from ten distinct sources, among them GeneDx, Labcorp, Ambry Genetics, the SPARK research study, the Autism Sequencing Consortium, and several major children’s hospitals.
When the researchers considered undetected cases, the limitations of genetic testing, and individuals with Phelan-McDermid syndrome who fail to meet the criteria for autism, they estimated a prevalence of 13.7 cases per 100,000 people.
This figure marks a significant shift from earlier estimates, and it points to a possible total of more than 45,000 people in the United States who could be living with Phelan-McDermid syndrome.
Why Genetic Testing Could Matter
According to the researchers, expanding who can get genetic testing could help find people who now have no diagnosis.
The Seaver Autism Center’s Director, Joseph D. Buxbaum, PhD, co-founder of the Autism Sequencing Consortium, was quoted “We recommend that every child with autism undergo genetic testing, because knowledge is power,” as the senior author of the paper.
“These genetic findings allow researchers to design more targeted clinical trials for potential therapies. I truly believe that within the next five years, we’ll see successful examples of new treatments coming from these genetic discoveries.”
The Gap Between Known and Estimated Cases
Tess Levy, MSc, a certified genetic counselor at the Seaver Autism Center and first author of the paper, said the large gap between known and estimated cases is likely largely due to the fact that many individuals with developmental disabilities and autism are never offered genetic testing.
Tests that do not adequately evaluate the SHANK3 gene, along with insurance barriers, can prevent families from getting a correct diagnosis.
“This study confirms what many families, clinicians, and advocates have suspected for years,” said CureSHANK Board Chair, Geraldine Bliss. “There are likely tens of thousands of individuals with Phelan-McDermid syndrome who have never received a genetic diagnosis. At a time when multiple therapeutics are advancing into clinical trials, finding these individuals has never been more important.”
Research into Phelan-McDermid syndrome is currently experiencing a significant period of activity, and several clinical trials are now underway. Among these are precision medicine approaches aimed at the biology underlying the disorder.
Beyond understanding the cause of their symptoms, a genetic diagnosis can now open doors for people with the condition and their families. It may allow them to connect with specialized medical care, research studies, clinical trials, patient support networks, and potentially disease-modifying treatments.
Neuren Pharmaceuticals and the Study’s Funding
CureSHANK and Neuren Pharmaceuticals have backed the research. It was Neuren Pharmaceuticals that started the landmark PMS prevalence study with the Seaver Autism Center at Mount Sinai and CureSHANK, and Rachel Groth, PhD, Head of External Innovation and Patient Advocacy at Neuren Pharmaceuticals, said the effort is needed because identifying these individuals has become an ethical imperative as new treatments move closer to reality.
“Patients cannot benefit from these advances if they never receive a diagnosis,” she said.
This research has been called one of the most thorough efforts to date at figuring out how many people may have Phelan-McDermid syndrome.
The Broader Message on Precision Medicine
The findings support CureSHANK’s efforts to increase access to genetic testing and align with the aims of Start Genetic, a worldwide campaign promoting awareness that encourages patients, families, health care providers, and advocacy groups to consider genetic causes first.
The point being made is that no matter how precise a new medical approach becomes, it can only help people who have first been recognized and diagnosed as sick.
What the Numbers Mean
Ten data sources were drawn together to produce the figure, and the researchers factored in undiagnosed cases, genetic testing limitations, and people with Phelan-McDermid syndrome who do not meet the criteria for autism.
This research is among the most thorough efforts to calculate the prevalence of Phelan-McDermid syndrome, and the results indicate that over 45,000 individuals in the United States may carry the condition.
The research was published as “Prevalence of Phelan McDermid Syndrome Estimated To Be ~1:7300 Using a Multisource Model,” in the journal Autism Research, with the DOI 10.1002/aur.70297.
Clinical trials for targeted PMS treatments are now underway, and precision medicine approaches are being tested. Families can begin to see what a genetic diagnosis might actually change as these findings come to light.
The researchers suggest genetic testing for every child with autism, arguing that knowing a person’s genetic makeup is empowering. They also believe that within the next five years, the first successful treatments derived from these genetic discoveries may emerge.
- The researchers recommend genetic testing for every child with autism, because knowledge is power.
- They also believe that within the next five years, the first successful treatments derived from these genetic discoveries may emerge.
Source material: “This “rare” autism-linked genetic disorder may be far more common than scientists thought,” ScienceDaily.
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