Phelan-McDermid Syndrome (PMS): Researchers provide first prospective characterisation

In the first prospective study of its kind, Seaver Autism Center researchers at the Icahn School of Medicine at Mount Sinai provide new evidence of the severity of intellectual, motor, and speech impairments in a subtype of autism called Phelan-McDermid Syndrome (PMS).

The data are published online in the June 11 issue of the journal Molecular Autism.

Mutation or deletion of a gene known as SHANK3 is one of the more common single-gene causes of autism spectrum disorders and is critical to the development of PMS, a severe type of autism.

To date, clinicians have relied on case studies and retrospective reviews of medical records to understand the features of this disorder and how the clinical presentation relates to the extent of the genetic changes in the SHANK3 region.

In the first systematic and comprehensive prospective trial, researchers led by Alex Kolevzon, MD, Clinical Director of the Seaver Autism Center, under the direction of Joseph Buxbaum, PhD, Director of the Seaver Autism Center, enrolled 32 participants with SHANK3 deletions to comprehensively assess their clinical symptoms and examine how the size of the SHANK3 deletion correlated to those symptoms.

"Previous studies have not utilized prospective assessments to understand Phelan-McDermid Syndrome, and the prevalence of autism spectrum disorder has never been examined using gold-standard instruments" said Dr. Kolevzon.

"There is no established standard for assessing this type of autism, and our study provides important guidance in developing such a standard."

Of the 32 patients enrolled, 84 percent met criteria for an autism spectrum disorder. Seventy-seven percent of patients exhibited severe to profound intellectual disability, with 19 percent using some form of verbal communication.

Other common features included low muscle tone, gait disturbance, and seizures. The researchers also found that patients who had larger SHANK3 deletions had more severe disease.

"Our findings provide additional evidence of the significant impairment associated with SHANK3 deficiency," said Dr. Kolevzon.

"Also, knowing how large the deletion of the SHANK3 gene is may have important implications for medical monitoring and individualizing treatment plans. Results also provide much-needed guidance in developing a standardized methodology for evaluating the features of this disorder."

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