The heart-mind connection: Learning from and giving back to patients

The heart-mind connection: Learning from and giving back to patients

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By Nancy Butcher and Anne Bassett
Photograph courtesy of Matthew Wu

She’s been hearing the voices a little lately—the ones that aren’t really there. She sounds a bit different than other people when she speaks, and struggled in school until dropping out in grade 10. She’s been in and out of hospitals her whole life, starting with the surgery to fix the heart defect she was born with. And now, at 38 years old, she finally knows why.

She has 22q11.2 deletion syndrome (22q11.2DS), a common but underdiagnosed multisystem condition caused by the deletion of approximately 50 genes on one of the pair of chromosomes 22. It can affect nearly every system of the body. Although the usual estimate is that this deletion occurs in about 1 in every 2 000-4 000 live births, recent prenatal testing studies show a higher rate of about 1 in 350.(1, 2) Before the genetic deletion was identified as the cause, patients with 22q11.2DS used to be diagnosed with multiple different syndromes because of the variable clinical presentation. These included DiGeorge syndrome, velo-cardio-facial syndrome, and conotruncal anomaly face syndrome.

The major features of 22q11.2DS include birth defects, neurodevelopmental abnormalities, and later-onset neuropsychiatric conditions. For example, about 1 in 3 babies with 22q11.2DS have a serious congenital heart defect, such as tetralogy of Fallot, which requires surgical repair. During childhood, developmental delay and palatal anomalies that cause nasal speech often become apparent. As patients enter adolescence and adulthood, about 1 in 4 develop schizophrenia, making the 22q11.2 deletion the highest known molecular genetic risk factor for schizophrenia. Schizophrenia associated with the 22q11.2 deletion is clinically indistinguishable from idiopathic forms of schizophrenia and is responsive to standard antipsychotic treatments.

Our growing knowledge of the syndrome, including its changing face over the lifespan, is the fruit of a close collaboration between clinical practice and research over the past two decades. Advances in pediatric care now mean that more patients are living to adulthood. This knowledge has greatly improved clinical care and genetic counselling for patients and their families.(3) And new discoveries important for clinical care are still being made−a new association was identified between 22q11.2DS and early-onset Parkinson’s disease just last fall.(4) The increasing population of adults with 22q11.2DS has created a new need for advanced, multidisciplinary care informed by evidence-based medicine. Because 22q11.2DS can affect nearly every part of the body, patients and their families often need to visit multiple hospitals to see several specialists. Through a generous $4 million donation by The W. Garfield Weston Foundation, this need is now being met. The Dalglish Family Hearts and Minds Clinic for Adults with 22q11.2 Deletion Syndrome officially opened its doors last year at the Toronto General Hospital, University Health Network (UHN), with the first patient seen in February 2013. This is the world’s first multidisciplinary clinic devoted to adults with 22q11.2DS and their families.

The Dalglish Family Hearts and Minds Clinic provides a one-stop-shop for patients with 22q11.2DS and their families. The clinic is directed by Dr. Anne Bassett, Professor of Psychiatry and Full Member of the Institute of Medical Science at the University of Toronto (U of T) and The Dalglish Family Chair in 22q11.2 Deletion Syndrome together with the co-director, Dr. Alan Fung, Assistant Professor of Psychiatry at U of T. The ultimate goal for the clinic is to serve as a model of integrated and personalized care not only for 22q11.2DS, but also other complex conditions. The clinic team includes a nurse, a dietician, and a social worker, as well as doctors from multiple specialties, including cardiology, psychiatry, endocrinology, genetics, and neurology. Through close collaboration with the established 22q Deletion Syndrome Clinic at The Hospital for Sick Children, the plan is to develop an integrated transition clinic for teens and youths. The focus will be on preventative health care–especially preventing serious psychiatric illnesses like schizophrenia and/or ameliorating their effects.

Along with the focus on clinical care, research and education are major components of the mandate of The Dalglish Family Hearts and Minds Clinic. Trainees, researchers, and clinicians will gain expertise in 22q11.2DS and thus in managing complex multisystem disorders in adults. This is a major aspect of the vision for UHN. Researchers and their collaborators are examining the clinical challenges that patients with 22q11.2DS and their families face, especially in the areas of cardiology, psychiatry, and neurology. These include both basic and clinical research studies that are immediately translatable into patient care. An exciting new project to sequence the entire genome in hundreds of patients with 22q11.2DS using the latest technology, whole genome sequencing, may provide new insights into the genetic underpinnings of diseases and conditions associated with 22q11.2DS. This could help explain and predict, for example, why some people are born with heart defects, and others develop schizophrenia. There are implications not only for those with 22q11.2DS, but also for the millions of people worldwide with these common disorders.

The Dalglish Clinic shares a strong clinical and research relationship with the Toronto Congenital Cardiac Centre for Adults (TCCCA), where many adults with 22q11.2DS in the province receive world-class care for the associated cardiac defects. As 22q11.2DS is often undetected, patients sometimes receive their first diagnosis as adults at TCCCA. Working together with The Dalglish Clinic, patients receive the collaborative, multidisciplinary care necessary to manage their unique needs. The clinic is contributing to the Peter Munk Cardiac Centre Biobank and database and enabling new research studies in 22q11.2DS. Biobanking of these tissue specimens may permit the development of molecular therapies for patients with 22q11.2DS and its component disorders. By facilitating both clinical and basic research in 22q11.2DS, it is hoped that The Dalglish Clinic will help answer the questions that are most important to the patients and their families.

Nancy Butcher, MSc
PhD student, Institute of Medical Science, University of Toronto
Clinical Genetics Research Program, Centre for Addiction and Mental Health
Anne S. Bassett, MD, FRCPC
Canada Research Chair in Schizophrenia Genetics and Genomic Disorders
Dalglish Chair in 22q11.2 Deletion Syndrome
Professor of Psychiatry, University of Toronto
Full Member, Institute of Medical Science, University of Toronto
Associate Staff, Division of Cardiology, University Health Network
Associate Member, Canadian College of Medical Geneticists
Director, Clinical Genetics Research Program
1. Wapner RJ, Martin CL, Levy B, et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012;367(23):2175-84.
2. Costain G, McDonald-McGinn DM, Bassett AS. Prenatal genetic testing with chromosomal microarray analysis identifies major risk variants for schizophrenia and other later-onset disorders. Am J Psychiatry. 2013;170(12):1498.
3. Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011;159(2):332-9.
4. Butcher NJ, Kiehl T-R, Hazrati L-N, et al. Individuals with 22q11.2 deletion syndrome are at increased risk of early-onset Parkinson disease: Identification of a novel genetic form of Parkinson disease and its clinical implications. JAMA Neurology. 2013(70):1359-66.