Rare Disease Cohorts | Overview
Ten million children are affected by a rare disease with a genetic cause. Yet, treatments for rare diseases are limited due to the unique challenges of rare disease research. Pediatric patients affected by the same rare disease (cohorts) are few in number and tend to be geographically widely distributed. So, finding a way to combine small cohorts is extremely valuable.
About the CRDC initiative
The Children's Rare Disease Cohort (CRDC) initiative at Boston Children’s Hospital fuels genomics research (the study of all of a person's genes) around 46 rare disease cohorts to expedite pediatric precision medicine. The information gathered supports our internal and collaborative research projects, and under certain circumstances, the data also can inform clinical treatment of participating families. Enrollment and sample collection can be completed from the comfort of your home.
The CRDC is an institution-wide initiative to better understand the molecular abnormalities associated with rare disease phenotypes. We envision this will allow more rapid diagnosis, in some cases personalized-treatment strategies with current medications, and identification of new targets that will facilitate development of new therapies for children with rare disease.
David Williams, MD, Boston Children's Hospital Chief of the Division of Hematology/Oncology
We have developed a broadly sharable database and have engaged several external partners, including GeneDx, Genuity Science, Emedgene, and Clinithink. Within its first year, the CRDC launched 15 studies of rare pediatric-onset Mendelian diseases, including epilepsy and inflammatory bowel disease (IBD). Together, these studies enrolled 2,441 participants and collected data from medical records and research surveys.
CRDC leadership
The CRDC is led by the CRDC Steering Group (Alan Beggs, PhD; Annapurna Poduri, MD, MPH; Janet Chou, MD; Piotr Sliz, PhD; and Shira Rockowitz, PhD) that is guided by a Scientific Advisory Board (Heidi Rehm, PhD, FACMG; Michael Talkowski, PhD; Robert Gentleman, PhD; Christopher Walsh, MD, PhD; Ingrid Holm, MD, MPH; Elizabeth Engle, MD; David Williams, MD). The cohort selection process is led by Timothy Yu, MD. PhD; Leonard Rappaport, MD, MS; Siddharth Srivastava, MD; Margaret Kenna, MD, MPH, FACS, FAAP; and Olaf Bodamer, MD, PhD, FACMG, FAAP, and includes all CRDC faculty members. The CRDC is implemented by Research Computing under the direction of Shira Rockowitz, PhD; and Piotr Sliz, PhD. As of today, 46 rare disease cohorts have been approved to join the CRDC. The table below lists the participating clinicians, their contact information, and area of interest for projects that are operational with IRB protocols in place.
Pediatric rare disease cohorts
More than 41 pediatric rare disease cohorts are now participating in the CRDC.
| Cohort | Primary Investigator | Contact Information |
|---|---|---|
| Epilepsy and related disorders | Annapurna Poduri, MD, MPH, Department of Neurology | epilepsygenetics@childrens.harvard.edu |
| Inflammatory bowel disease (Crohn's disease, ulcerative colitis, indeterminate colitis, very early onset inflammatory bowel disease) | Scott Snapper, MD, PhD, Division of Gastroenterology, Hepatology and Nutrition | scott.snapper@childrens.harvard.edu |
| Immunodeficiencies, autoimmunity, and immune dysregulation | Janet Chou, MD, Division of Immunology | janet.chou@childrens.harvard.edu |
| Congenital sensorineural hearing loss | Margaret Kenna, MD, MPH, FACS, FAAP, Department of Otolaryngology and Communication Enhancement | BAGHLstudy@childrens.harvard.edu |
| Ehlers-Danlos syndrome or related conditions | Joel Hirschhorn, MD, PhD, Division of Endocrinology | joel.hirschhorn@childrens.harvard.edu |
| Idiopathic short stature | Joel Hirschhorn, MD, PhD, Division of Endocrinology | joel.hirschhorn@childrens.harvard.edu |
| Disorders of sexual development/severe hypospadias | Joel Hirschhorn, MD, PhD, Division of Endocrinology | joel.hirschhorn@childrens.harvard.edu |
| Bronchiectasis | Benjamin Raby, MD, MPH, Division of Pulmonary Medicine | benjamin.raby@childrens.harvard.edu |
| Childhood interstitial and diffuse lung disease | Benjamin Raby, MD, MPH, Division of Pulmonary Medicine | benjamin.raby@childrens.harvard.edu |
| Congenital diarrheas and enteropathies (infantile onset chronic diarrhea or malabsorption) |
Jay Thiagarajah, MD, PhD, Division of Gastroenterology, Hepatology and Nutrition | enteropathy@childrens.harvard.edu |
| Ultra-rare cohorts | Alan Beggs, PhD, Division of Genetics and Genomics | beggs@enders.tch.harvard.edu |
| Cerebral palsy and related disorders (infancy or older) | Siddharth Srivastava, MD, Department of Neurology | siddharth.srivastava@childrens.harvard.edu |
| Ectodermal dysplasia and cleft lip and/or palate | Ingrid Ganske, MD, Department of Plastic & Oral Surgery | ingrid.ganske@childrens.harvard.edu |
| Myopathies and dystrophies | Alan Beggs, PhD, Division of Genetics and Genomics | beggs@enders.tch.harvard.edu |
| Severe early onset major depression (documented before the age of 14) | Joseph Gonzalez-Heydrich, MD, Department of Psychiatry | DNP.Studies@childrens.harvard.edu |
| Disorders impacting social and cognitive functioning (ADHD, OCD, dyslexia, or a related disorder) | Ryan Doan, PhD, Department of Pediatrics | |
| Severe pediatric COVID-19 | Adrienne Randolph, MD, MSc, Department of Anesthesiology, Critical Care and Pain Medicine Janet Chou, MD, Division of Immunology |
adrienne.randolph@childrens.harvard.edu |
| Severe chronic pain and insensitivity to pain | Charles Berde, MD, PhD, Department of Anesthesiology, Critical Care and Pain Medicine | charles.berde@childrens.harvard.edu |
| Anemias and iron disorders | Mark Fleming, MD, DPhil, Department of Pathology | mark.fleming@childrens.harvard.edu |
| Neonatal Intensive Care Unit | Sarah Morton, MD, PhD, Division of Newborn Medicine | sarah.morton@childrens.harvard.edu |
| Peripheral vestibular disorders | Eliot Shearer, MD, PhD, Department of Otolaryngology and Communication Enhancement | Chives.Study@childrens.harvard.edu |
| Nephrotic syndrome/glomerular disease (childhood onset nephrotic syndrome) | Matt Sampson, MD, MS, Division of Nephrology | bigkids.biobank@childrens.harvard.edu |
| Osteogenesis Imperfecta/multiple fractures (clinical diagnosis of OI OR 3 or more long bone fractures or any spinal compression fractures before puberty) | Christina Jacobsen, MD, PhD, Division of Endocrinology | 617-919-2035 |
| Psychosis/Psychiatry | David Glahn, PhD, Department of Psychiatry | david.glahn@childrens.harvard.edu |
| Pediatric urinary tract stone disease | Amar Majmundar, MD, PhD, Division of Nephrology | amar.majmundar@childrens.harvard.edu |
| Bone marrow failure and leukemia predisposition | Akiko Shimamura, MD, PhD, Cancer and Blood Disorders Center | akiko.shimamura@childrens.harvard.edu |
| Brain malformations | Christopher Walsh, MD, PhD, Division of Genetics | christopher.walsh@childrens.harvard.edu |
| Congenital heart disease and autism spectrum disorders | Maya Chopra, MD, FRACP, Department of Neurology | maya.chopra@childrens.harvard.edu |
| Hyperkinetic disorders | Claudio Melo de Gusmao, MD, Department of Neurology | claudio.degusmao@childrens.harvard.edu |
| Infantile esotropia | Mary Whitman, MD, PhD, Department of Ophthalmology | mary.whitman@childrens.harvard.edu |
| Complex fetal cases | Monica Wojcik, MD, Division of Newborn Medicine | monica.wojcik@childrens.harvard.edu |
| Cornelia de Lange syndrome | Philip Boone, MD, PhD, Division of Genetics and Genomics | philip.boone@childrens.harvard.edu |
| Sudden unexpected death in pediatrics | Richard Goldstein, MD, Department of General Pediatrics | richard.goldstein@childrens.harvard.edu |
| Hereditary spastic paraplegia | Darius Ebrahimi-Fakhari, MD, PhD, Department of Neurology | darius.ebrahimi-fakhari@childrens.harvard.edu |
| Precocious puberty | Stephanie Roberts, MD, Division of Endocrinology | stephanie.roberts@childrens.harvard.edu |
| Cerebrovascular disorders/vascular malformations of the brain | Siddharth Srivastava, MD, Department of Neurology | siddharth.srivastava@childrens.harvard.edu |
| Disorders of voiding | Nina Mann, MD, Division of Nephrology | nina.mann@childrens.harvard.edu |
| Bladder exstrophy-epispadias complex | Ted Lee, MD, MSc, Department of Urology | ted.lee@childrens.harvard.edu |
| Intestinal malrotation and volvulus |
Christopher Duggan, MD, MPH, Division of Gastroenterology, Hepatology and Nutrition Wen-Hann Tan, BMBS, Division of Genetics and Genomics |
|
| Graves disease |
Jessica Smith, MD, Division of Endocrinology Janet Chou, MD, Division of Immunology |
janet.chou@childrens.harvard.edu |
| Precision epilepsy | Annapurna Poduri, MD, MPH, Department of Neurology | epilepsygenetics@childrens.harvard.edu |