New study defines rare TCF7L2-related neurodevelopmental disorder

Researchers have completed the largest study to date of TCF7L2-related neurodevelopmental disorder (TRND), a rare genetic condition caused by changes in the TCF7L2 gene, which plays an important role in brain development.

By analyzing 76 patients from around the world in collaboration with sites across 14 countries and several US cities, including Philadelphia and Boston, the team found that the most common identifying features were speech delay, autism, developmental delays, vision problems such as nearsightedness, and orthopedic issues affecting the muscles and skeleton. Many patients also had distinctive facial features, helping researchers better define the condition and improve recognition and diagnosis.

The study, led by Senior Author, David Fajgenbaum, MD, MBA, MSc, and other researchers in the Perelman School of Medicine at the University of Pennsylvania, was recently published in Genetics in Medicine.

"By defining the genetic and clinical features of TRND across a large international cohort, we hope to improve recognition of the condition and accelerate future research regarding longitudinal outcomes and potential therapies," said first-author on the study Sally Nijim, MD, MBA, a resident physician-researcher at Mass General Brigham, who conducted the research while a medical student at Penn Medicine. The study also found that symptoms can vary widely and identified a possible link between certain TCF7L2 variants and type 2 diabetes in adults that warrants further study. The TRND Network is an initiative borne out of this study which connects TRND patients, families, physicians, and researchers, and a prospective natural history registry for longitudinal study of TRND patients is available to patients for enrollment (https://trndnetwork.org/join-the-registry/).