Link Between 22q and Mental Illness Studied

Published on in CHOP News

October 3, 2013 — Genetics experts from The Children’s Hospital of Philadelphia (CHOP) are among the top leaders of a major international collaboration researching why patients with chromosome 22q11.2 deletion syndrome have an elevated risk of schizophrenia and other psychiatric illnesses.

Discovering genes implicated in the deletion syndrome, a multisystem disorder, may offer important clues to the biological causes of mental illness in the general population.

Donna McDonald-McGinn, MS, CGC, program director of the 22q and You Center at The Children’s Hospital of Philadelphia, is the co-director of the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome, which has just received a $12 million, four-year grant from the National Institute of Mental Health, part of the National Institutes of Health. The consortium brings together caregivers and scientists from 22 clinical centers and five genotyping sites throughout the world.

Co-directing the overall consortium with McDonald-McGinn is Raquel E. Gur, MD, PhD, director of the Neuropsychiatry Program at the Perelman School of Medicine at the University of Pennsylvania. McDonald-McGinn and Gur, who frequently collaborate on chromosome 22q research, are also principal investigators of the project’s sites at their respective institutions — McDonald-McGinn at CHOP; and Gur at Penn Medicine.

Under-recognized syndrome may affect many parts of body

Found in approximately 1 in 4,000 live births, 22q11.2 deletion syndrome (22q11.2 DS) involves birth defects and developmental and behavioral differences occurring across the life span. Resulting from the absence of a DNA sequence on the long arm of chromosome 22, the syndrome has many possible signs and symptoms that may affect almost any part of the body, including the heart, palate, the immune and endocrine systems, and the kidneys. Some patients may have seizures, hearing loss, scoliosis, or feeding and swallowing problems.

Among the broad range of symptoms in this frequently under-recognized disorder, most children with 22q11.2 DS have developmental delays, including learning disabilities and delays in language emergence. Some may also have autism spectrum disorder, attention-deficit hyperactivity disorder, anxiety or obsessive-compulsive disorder.

When entering adolescence or young adulthood, approximately 25 to 30 percent of patients are at risk of developing schizophrenia, much higher than the one percent rate in the general population.

The consortium’s research tools will include whole-genome sequencing to uncover genetic variation among patients with chromosome 22q11.2 DS. The Children’s Hospital of Philadelphia, which has a long-standing research and clinical program focused on this condition, has evaluated over 1,200 patients, making it the world’s largest center of its kind.

CHOP has deep history, experience in this disorder

Two genetics researchers with global prominence in studying this diagnosis, Beverly S. Emanuel, PhD, and Elaine Zackai, MD, are co-investigators at CHOP’s site in the Brain and Behavior Consortium. Among many other accomplishments, in 1995 both scientists were on the team that created an early genetic map of chromosome 22, setting the stage for it to become the first chromosome sequenced in the Human Genome Project.

CHOP’s 22q and You Center is the largest existing clinical program for the deletion syndrome.

“Patients travel from around the globe to receive comprehensive, family-centered care at our center,” said McDonald-McGinn. “We have more than 15 subspecialists who are themselves considered world experts in treating both the frequent and rare medical and developmental differences caused by the 22q11.2 deletion. Moreover, the success of the CHOP program is directly related to the dedication of these team members, who rise to the occasion over and over again to provide state-of-the art care for this complex multisystem disorder.”

Study may inform broader treatments for schizophrenia

While focusing on the genetic roots of psychiatric disorders in 22q11.2 DS, the consortium leaders expect to identify biological pathways leading to schizophrenia in the broader population, with the hope that such data may inform novel, more effective treatments. “The knowledge generated can provide a window to the brain that will benefit millions throughout the world,” said Gur.

McDonald-McGinn added, “Not only does this grant demonstrate the commitment by the National Institute of Mental Health to better understand the brain and psychiatric illness, but the effort highlights the importance of international collaborations in working together toward improved patient care and long-term outcomes.”

McDonald-McGinn is a clinical professor of Pediatrics at Penn in addition to her position at CHOP. In addition to CHOP and Penn Medicine, participating academic sites include Albert Einstein College of Medicine, Duke University, Emory University, SUNY Syracuse, UCLA and UC Davis, in the U.S.; as well as sites in Cardiff, Dublin, Geneva, Leuven, London, Maastricht, Madrid, Mallorca, Marseilles, Newcastle, Australia; Rome, Santiago, Chile; Tel Aviv; Toronto; and Utrecht. The NIH grant supporting the Consortium is U01MH101719.


John Ascenzi, Children’s Hospital of Philadelphia, 267-426-6055,