A more precise approach to dyslexia

Jeffrey R. Gruen, M.D., professor of pediatrics and genetics, is taking a holistic view in working to remedy learning disabilities. Focusing on reading, attention, and mathematics disabilities, Gruen and his colleagues are preparing to follow around 3,200 first-graders in New Haven Public Schools (NHPS) over five years.

The new study, called the New Haven Lexinome Project (NHLP) and supported by a grant from the New York-based Manton Foundation, focuses on “genes-by-environment” effects: Gruen’s team is studying how home and cultural environments interact with a child’s genetics to influence his or her learning.

Says Gruen, “Disabilities in schoolchildren cost billions for federal, state, and local intervention programs. We hope to improve the effectiveness of those efforts by harnessing the predictive tool of genetics to target the kids who can benefit most from help, and to precisely match them with their optimal intervention.”

The NHLP builds on Gruen’s previous work in the field. In 2005 the journal Science described his discovery of the gene DCDC2—one of just a handful of genes associated with dyslexia—as the fifth most important breakthrough of that year. In 2008 Gruen coined the term human lexinome to capture all of the genes and specific loci on human chromosomes that appear to play a role in the development of language, expression, and reading.

In recent years Gruen has worked to hone an approach he calls “precision education.” In 2009, with the support of a $5 million grant from the Manton Foundation, he was the principal investigator of a multicenter genetic study of dyslexia in minorities, focusing on Hispanic-American and African-American children, called the Yale Genes, Reading, and Dyslexia (GRaD) Study. Its goal was to find genetic markers that can identify children at risk for dyslexia well before the children begin to fail in school, so that intervention could be started early, when it’s most effective.

The NHLP takes this research a step further. Children with dyslexia can have additional disabilities that span more than one domain, and hence the need to gather more information. Gruen’s aim is to know as much as possible about how genes and the type of learning intervention a child receives interact with each other. Whereas the GRaD Study focused on presymptomatic screening, the goal of the NHLP is to use genetics to predict response-to-intervention, and to inform the optimal intervention for each student with learning disabilities.

The team will selectively enroll qualified students for individual cognitive assessments, classroom and testing performance, family life and background, culture, serial magnetic resonance imaging of brain structure and function, and comprehensive genomic analyses. Once they reach the second grade, some students will also participate in an intense intervention with specially trained teachers.

By mid-October the NHLP had enrolled 87 families. The researchers are focused on recruitment and testing in first grade classes. The target for the study’s conclusion and results is 2021.

“The School of Medicine is deeply appreciative of this further encouragement and support from the Manton Foundation, an institution that has a strong record in the advancement of important work on behalf of underserved, urban communities,” said Dean Robert J. Alpern, M.D., Ensign Professor of Medicine. “This new grant allows the school to continue its ground-breaking genetics research and, equally important, to apply discoveries and progress toward improving human lives.”

Sometime in the future, Gruen says he hopes district-wide screening can be implemented to identify children at high risk for learning disabilities, and then to match them to a precisely-designed curriculum effective for a child’s unique genomic sequence.

“We know that dyslexia can respond to intervention programs that address multiple learning modalities and are offered in early grades,” Gruen says. However, “often the diagnosis and intervention come too late after a child has experienced repeated academic failures, and when the child is less likely to respond,” he says.

The Manton Foundation was established in New York City in 1991 by Sir Edwin and Lady Manton to support the arts, education, health care, cultural preservation, and medical research.