Birth… the beginning of a family’s story.

But for families of babies born with a rare genetic disease, the story is one fraught with challenges on their journey to an accurate diagnosis and appropriate care.

Imagine if we could change the narrative for those families from the very start.

Rady Children’s Institute for Genomic Medicine is helping to rewrite the story for infants with rare diseases through BeginNGS^®.

BeginNGS is a novel health care delivery system designed to screen newborns for genetic diseases — and connect their doctors with effective interventions.

Genetic diseases are chronic, progressive, and can be life-threatening.

They may not appear until later in childhood; however, the effects may begin before symptoms manifest. The effects may be irreversible if not diagnosed and treated.

Sometimes the solution is as simple as a vitamin supplement.

Other times, the baby can receive cutting-edge gene therapy and grow up to be a typical healthy child, like Fitz Kettler, pictured here.

BeginNGS helps ensure each baby is screened for genetic conditions for which interventions exist, and helps physicians provide effective interventions in a timely manner.

What is BeginNGS?

BeginNGS is an RCIGM-led pilot that uses genome sequencing as a screening tool for newborns, to identify genetic conditions before infants get sick. The BeginNGS pilot is not about replacing the current biochemical newborn screening approach (for roughly 60 known conditions) – rather, it is a complement to the newborn screening processes and infrastructure that are already in place.

Technological advances in genomic sequencing have made it possible to return test results in just a few days at a lower cost.

As our understanding of genetic diseases grows, and the pace of therapeutic innovation accelerates, newborn screening by genomic sequencing may provide a more dynamic way of expanding the number of conditions.

Since the whole genome is sequenced, the screening can be rapidly expanded to include new disorders as effective interventions become available.

Screening newborns for ~400 genetic diseases with known intervention options using rWGS

Identifying rare disease earlier to facilitate access to Rapid Precision Medicine™

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By rewriting the beginning, we can help families end their diagnostic and therapeutic odysseys so they can fill their stories with hope.

— Stephen Kingsmore, MD, DSc
President & CEO, Rady Children's Institute for Genomic Medicine

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Early diagnosis of rare disease patients will open the door to ongoing monitoring of symptoms and gathering of critical natural history data

— Charlene Son Rigby
CEO, Rare-X

Why Now?

There are over 30 million rare disease patients in the United States and over 5,000 rare disease clinical trials underway. Ending the diagnostic and therapeutic odyssey is finally within our grasp. Without disruptive progress, precision medicine at scale isn’t possible. BeginNGS will help us identify rare disease patients earlier, increase clinical trial enrollment and rapidly progress rare disease treatment.

Join Us

Interested in partnering with us or learning more about the project?

How It Works

This pilot includes birthing hospitals throughout the U.S. and abroad.
Blood-spot samples will be collected at the time of birth and sent to the lab where WGS will be performed.
Genomic analysis and interpretation will be performed for ~400 early onset actionable genetic conditions.
If a positive screening result is detected, the treating physician will be provided with access to resources on medical management and available interventions. They will then discuss next steps with the family. Licensed and board-certified genetic counselors will be available for consultation.

Ready to Learn More?

Media Coverage

September 8, 2023

AJMCtv

Dr Stephen Kingsmore Describes the Participants of the BeginNGS Consortium

Dr. Stephen Kingsmore explains how the BeginNGS consortium members help the project to continually evolve.

Media Coverage

August 29, 2023

AJMCtv

Dr. Stephen Kingsmore Highlights Disparities Seen in Genetic Testing

AJMCtv: Stephen Kingsmore discusses the types of disparities seen in genetic testing as the BeginNGS phase 2 clinical trial is underway.

Media Coverage

August 14, 2023

Becker's Healthcare Podcast

Interview with Patricio A. Frias, President and CEO of Rady Children’s Hospital – San Diego

Becker's Healthcare Podcast: RCHSD President and CEO Patricio A. Frias shares the exciting innovative research being conducted at Rady Children's Institute for Genomic Medicine.

Media Coverage

August 14, 2023

AJMCtv

Dr Stephen Kingsmore Discusses Rapid Diagnostic Genome Sequencing Program for Newborns

Stephen Kingsmore, MD, DSc, president and CEO, at Rady Children's Institute for Genomic Medicine, shares details of the BeginNGS newborn screening program and its future goals.

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Genome-based newborn screening for severe childhood genetic diseases has high positive predictive value and sensitivity in a NICU pilot trial

Am J Hum Genet. 2024 Dec 5;111(12):2643-2667. doi: 10.1016/j.ajhg.2024.10.020. ABSTRACT Large prospective clinical trials are underway or planned that examine the clinical utility and cost effectiveness of genome-based newborn screening (gNBS). One gNBS platform, BeginNGS, currently screens 53,575 variants for 412 severe childhood genetic diseases with 1,603 efficacious therapies. Retrospective evaluation of BeginNGS in 618,290 subjects suggests adequate sensitivity and positive predictive value (PPV) to proceed to prospective studies. To inform pivotal clinical trial design, we undertook a pilot clinical trial. We enrolled 120 infants in a regional neonatal intensive care unit (NICU) who were not under consideration for rapid diagnostic genome sequencing (RDGS). Each enrollee received BeginNGS and two index tests (California state NBS and RDGS). California NBS identified 4 of 4 true positive (TP) findings (TP rate 3.6%, sensitivity 100%) and 11 false positive (FP) findings (PPV 27%). RDGS identified 41 diagnostic findings in 36 neonates (diagnostic rate

Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection

Am J Hum Genet. 2024 Dec 5;111(12):2618-2642. doi: 10.1016/j.ajhg.2024.10.021. ABSTRACT Genome-sequence-based newborn screening (gNBS) has substantial potential to improve outcomes in hundreds of severe childhood genetic disorders (SCGDs). However, a major impediment to gNBS is imprecision due to variants classified as pathogenic (P) or likely pathogenic (LP) that are not SCGD causal. gNBS with 53,855 P/LP variants, 342 genes, 412 SCGDs, and 1,603 therapies was positive in 74% of UK Biobank (UKB470K) adults, suggesting 97% false positives. We used the phenomenon of purifying hyperselection, which acts to decrease the frequency of SCGD causal diplotypes, to reduce false positives. Training of gene-disease-inheritance mode-diplotype tetrads in 618,290 control and affected subjects identified 293 variants or haplotypes and seven genes with variable inheritance contributing higher positive diplotype counts than consistent with purifying hyperselection and with little or no evidence of SCGD causality. With these changes, 2.0% of UKB470K adults were positive. In contrast,

NBSTRN Tools to Advance Newborn Screening Research and Support Newborn Screening Stakeholders

Int J Neonatal Screen. 2023 Oct 30;9(4):63. doi: 10.3390/ijns9040063. ABSTRACT Rapid advances in the screening, diagnosis, and treatment of genetic disorders have increased the number of conditions that can be detected through universal newborn screening (NBS). However, the addition of conditions to the Recommended Uniform Screening Panel (RUSP) and the implementation of nationwide screening has been a slow process taking several years to accomplish for individual conditions. Here, we describe web-based tools and resources developed and implemented by the newborn screening translational research network (NBSTRN) to advance newborn screening research and support NBS stakeholders worldwide. The NBSTRN’s tools include the Longitudinal Pediatric Data Resource (LPDR), the NBS Condition Resource (NBS-CR), the NBS Virtual Repository (NBS-VR), and the Ethical, Legal, and Social Issues (ELSI) Advantage. Research programs, including the Inborn Errors of Metabolism Information System (IBEM-IS), BabySeq, EarlyCheck, and Family Narratives Use Cases, have utilized NBSTRN’s tools and, in turn, contributed

The Promise and Perils of Next-Generation DNA Sequencing at Birth: Proceedings of a Workshop–in Brief

National Academies of Sciences, Engineering, and Medicine. 2023. The Promise and Perils of Next-Generation DNA Sequencing at Birth: Proceedings of a Workshop–in Brief. Washington, DC: The National Academies Press. https://doi.org/10.17226/2724 Pilot programs are employing whole genome sequencing and whole exome sequencing during the newborn phase both within the United States and internationally. While sequencing offers the opportunity to screen for treatable but not clinically evident conditions early in a child’s life, it raises a host of ethical, legal, and social questions for experts, including parents, to consider. The National Academies Roundtable on Genomics and Precision Health hosted experts from health care, industry, academia, the federal and state governments, and patient and consumer advocacy groups for a June 2023 workshop. Participants, including RCIGM investigator Nathaly Sweeney, explored the potential benefits and harms, data security, and health equity considerations for the widespread utilization of newborn genome sequencing in the U.S. This publication summarizes

Assessing Diversity in Newborn Genomic Sequencing Research Recruitment: Race/Ethnicity and Primary Spoken Language Variation in Eligibility, Enrollment, and Reasons for Declining

Clin Ther. 2023 Jul 8:S0149-2918(23)00220-5. doi: 10.1016/j.clinthera.2023.06.014. Online ahead of print. ABSTRACT PURPOSE: Diagnostic genomic research has the potential to directly benefit participants. This study sought to identify barriers to equitable enrollment of acutely ill newborns into a diagnostic genomic sequencing research study. METHODS: We reviewed the 16-month recruitment process of a diagnostic genomic research study enrolling newborns admitted to the neonatal intensive care unit at a regional pediatric hospital that primarily serves English- and Spanish-speaking families. Differences in eligibility, enrollment, and reasons for not enrolling were examined as functions of race/ethnicity and primary spoken language. FINDINGS: Of the 1248 newborns admitted to the neonatal intensive care unit, 46% (n = 580) were eligible, and 17% (n = 213) were enrolled. Of the 16 languages represented among the newborns’ families, 4 (25%) had translated consent documents. Speaking a language other than English or Spanish increased a newborn’s likelihood of being

Response to Grosse et al

Am J Hum Genet. 2023 Jun 1;110(6):1017. doi: 10.1016/j.ajhg.2023.05.004. NO ABSTRACT PMID:37267897 DOI:10.1016/j.ajhg.2023.05.004

NEWBORN GENOMIC SEQUENCING

to end the diagnostic odyssey

Birth… the beginning of a family’s story.

Imagine if we could change the narrative for those families from the very start.

Rady Children’s Institute for Genomic Medicine is helping to rewrite the story for infants with rare diseases through BeginNGS®.

Genetic diseases are chronic, progressive, and can be life-threatening.

Sometimes the solution is as simple as a vitamin supplement.

BeginNGS helps ensure each baby is screened for genetic conditions for which interventions exist, and helps physicians provide effective interventions in a timely manner.

What is BeginNGS?

As our understanding of genetic diseases grows, and the pace of therapeutic innovation accelerates, newborn screening by genomic sequencing may provide a more dynamic way of expanding the number of conditions.

Screening

Rapid Intervention

By rewriting the beginning, we can help families end their diagnostic and therapeutic odysseys so they can fill their stories with hope.

Early diagnosis of rare disease patients will open the door to ongoing monitoring of symptoms and gathering of critical natural history data

Why Now?

Join Us

How It Works

Ready to Learn More?

Upcoming BeginNGS Presentations & Events

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Rady Children’s Institute for Genomic Medicine is helping to rewrite the story for infants with rare diseases through BeginNGS^®.