Research Spotlight: Genetic Testing Practices, Indications and Results in Patients with Down Syndrome

Stephanie L. Santoro, MD, director of Quality Improvement Research for the Down Syndrome Program at Mass General for Children is the senior author of a recent study published in the American Journal of Medical Genetics, Part C, Beyond Chromosome Analysis: Additional Genetic Testing Practice in a Down Syndrome Clinic.

What Question Were You Investigating?

Down syndrome (DS) and other genetic conditions have been reported to co-occur in the same person. This study sought to examine the genetic evaluation beyond chromosome analysis of individuals with DS at one DS specialty clinic.

What Methods or Approach Did You Use?

We conducted a retrospective chart review focusing on:

• Genetic testing performed beyond chromosome analysis
• The indication for the genetic testing
• The results of the tests

The charts of 637 individuals with DS were reviewed. Demographic information was collected and summary statistics, including mean and frequency, were calculated.

What Did You Find?

We reviewed the charts of 637 individuals with Down syndrome followed in our program, and found:

• Overall, 146 genetic tests in addition to routine chromosome analysis were performed on 92 individuals with DS
• Tests included chromosomal microarray, gene panels, and whole exome sequencing, and were performed for the indication of: autism spectrum disorder, celiac disease, dementia, hematologic diseases and others
• Eleven individuals with DS were found to have a second genetic diagnosis

What are the Clinical Implications?

Overall, we felt that additional genetic testing beyond chromosome analysis is a reasonable consideration for patients with DS who have features suggestive of a secondary diagnosis.

What are the Next Steps?

We propose that a practicing clinical geneticist may consider additional genetic testing when encountering a patient with

• a co-occurring condition that is uncommon in DS for which there is reasonable genetic testing available
• a co-occurring condition for which a genetic basis is often found in the general population when reasonable genetic testing is performed
• a unique constellation of features which suggest a specific co-occurring condition with a genetic basis, or
• symptom(s) for which there is a genetic basis and genetic testing would directly impact management or treatment.

Future study could evaluate the yield of testing for these proposed situations.

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.