Deep interpretation of complex clinical cases

This page is dedicated to the Deep Interpretation of Complex Clinical Cases program supported by the Boston Children’s Rare Disease Collaborative (CRDC). For more information about the CRDC, please visit our home page. Established in 2018, the CRDC supports pediatric rare disease research and provides families with genetic diagnoses that enable personalized treatments, including precision medicine and targeted therapies.

Dr. Wendy Chung speaking at the 2025 Pediatric Rare Disease Summit

The Deep Interpretation of Complex Clinical Cases program is led by Dr. Wendy Chung, Physician in Chief, Dr. Shira Rockowitz, Data Science Director, and Dr. Monica Wojcik, Medical Director, and supports reanalysis and reinterpretation of, or a “second look" at, clinical genetic testing when this genetic testing does not initially find a diagnosis.

When children have complex medical conditions, clinicians routinely order clinical genetic testing. About 30% of the time, this testing provides a genetic diagnosis to help better understand the cause, management, and potential treatment for a medical condition. For the other 70%, the search for answers continues.

Over time, new genes are linked to diseases as we learn more about genetics. As technologies advance, new analyses can help solve some of these cases using existing genetic data. Any patient for whom clinical genetic testing (whole exome sequencing or whole genome sequencing) is ordered through BCH will be automatically included in this clinical reanalysis program.

Findings from these reanalyses and reinterpretation are confirmed by GeneDx before being reported. The CRDC Data Science team uses advanced tools to help identify genetic variants and supports these efforts.

Key outcomes

Sankey diagram of findings from clinical reanalysis

As of April 2025, variants have been identified in 32 patients of which 53% are leading to changes in care.

Patient care

Patients and their families with complex medical conditions can be seen by expert multidisciplinary teams at Boston Children’s, which include the Complex Care Service and Integrated Care Program.

Investigators

Divisions

Notable publications by investigators

  1. Improvement of variant reclassification in genetic neurodevelopmental conditions.
  2. Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine.
  3. Phenotype-Driven Molecular Genetic Test Recommendation for Diagnosing Pediatric Rare Disorders.
  4. Rare disease diagnosis using knowledge guided retrieval augmentation for ChatGPT.

Disease support organizations

Exceptional Lives

Exceptional Lives is a not-for-profit organization that provides information on resources and services for families of children with special needs. This platform is especially useful for residents of Massachusetts and Louisiana, as it helps parents and caregivers find doctors and programs near them. For residents of other states, the site provides a helpful guide on available national programs.

Rare Disease Diversity Coalition

Rare Disease Diversity Coalition (RDCC) was launched by the Black Women’s Health Imperative to address the extraordinary challenges faced by underserved populations with rare diseases. The Coalition brings together rare disease experts, health and diversity advocates, and industry leaders to identify and advocate for evidence-based solutions to alleviate the disproportionate burden of rare diseases on historically marginalized populations.

Undiagnosed Disease Network Foundation (UDNF)

UDNF is a nonprofit organization led by and for patients and their families to foster collaboration among patients, clinicians, and scientists to enhance the quality of life of undiagnosed and ultra-rare disease patients.

Beacon

Beacon is a UK-based non-profit organization that is building a united rare disease community with patient groups at its heart.

Trusted sites