Rare Disease Cohorts

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	www.doanlab.org/join-a-study DoanLab@childrens.harvard.edu ryan.doan@childrens.harvard.edu
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	christopher.duggan@childrens.harvard.edu wen-hann.tan@childrens.harvard.edu
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

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