Toward Universal Newborn Screening for Angelman Syndrome: The Early Check Approach

Quick Overview

Kay Kucera, a research director at the Newborn Screening and Genetics Laboratory at RTI, presented on the Early Check program in North Carolina and their efforts to implement newborn screening for Angelman syndrome. Newborn screening is a public health service that currently screens for about 32 to 35 different conditions, and adding a new condition requires collecting data to show feasibility and benefit. The Early Check program aims to pilot newborn screening efforts and generate data to inform public health policy. They offer voluntary infant screening to parents in North Carolina and evaluate outcomes for screen-positive infants. The program has been running for over four years and has screened for conditions such as spinal muscular atrophy and Fragile X syndrome. They are currently screening for Duchenne muscular dystrophy and preparing to add screening for other conditions, including Angelman syndrome. The program is a collaboration between RTI International, the North Carolina State Laboratory of Public Health, and clinical centers. The screening process includes education, testing, reporting results, genetic counseling, confirmatory testing, and long-term follow-up. The assay for Angelman syndrome is methylation-based and uses dry blood spot specimens. The program is working on assay validation, developing protocols, and updating documentation before launching screening. The goal is to optimize the workflow and minimize false positive and false negative results. The program has enrolled over 24,000 newborns so far.

Introduction

In this talk, we will discuss the Early Check program in North Carolina and its efforts to implement newborn screening for Angelman syndrome in a research environment. The Early Check program aims to collect data to demonstrate the feasibility and benefits of newborn screening for various conditions. This talk will provide an overview of the program’s goals, the conditions currently being screened, and the collaborative efforts involved.

The Need for Newborn Screening Data

Newborn screening is a crucial public health service provided to all newborns. Currently, states screen for around 32 to 35 different conditions. However, before adding a new condition to the screening panel, extensive data must be collected to ensure its feasibility and appropriateness. This creates a catch-22 situation where screening cannot be mandated without data, but data can only be generated through screening. The Early Check program addresses this challenge by piloting newborn screening efforts and collecting the necessary data.

Goals of the Early Check Study

The Early Check study has several goals. Firstly, it offers voluntary infant screening to parents in North Carolina under a research protocol. Secondly, it evaluates the outcomes of infants identified as screen positives. Additionally, the study examines the impact on families and parents. Ultimately, the data collected through Early Check will inform public health policy and facilitate the transition to standard newborn screening if appropriate.

Early Check Program Overview

The Early Check program offers parents in North Carolina the choice to participate in additional screening for their newborns. With approximately 120,000 births per year in the state, the program aims to generate data and evidence through various opportunities. These include determining population prevalence, detecting early symptoms and onset, examining phenotype-genotype correlation, and testing pre-symptomatic treatments.

Conditions Currently Screened and Future Plans

The Early Check program has been running for over four years and has already screened for conditions such as spinal muscular atrophy and Fragile X syndrome. Currently, the program is screening for Duchenne muscular dystrophy. Plans are underway to add screening using sequencing for a panel of over 200 conditions actionable in early childhood, as well as a panel for conditions less actionable in early childhood and a genetic risk score for type 1 diabetes. The program is also preparing to screen for chromosome 15 imprinting disorders, including Angelman, Prader-Willi, and Dup15q syndromes, as well as congenital cytomegalovirus and a panel of lysosomal storage disorders.

Collaboration and Funding

The Early Check program is a large collaboration led by RTI International, a nonprofit research institute. The program works closely with the North Carolina State Laboratory of Public Health and clinical centers such as Duke University, UNC Chapel Hill, and Wake Forest Medical Center. Funding for the program comes from a variety of public and private sources, including foundations and pharmaceutical companies.

The Comprehensive Approach of Early Check

Early Check is not just about screening and lab tests; it is an entire system that needs to be tested. The program provides education to the general public during the recruitment process, offers testing for enrolled newborns, reports results through a web portal, provides genetic counseling for positive results, and offers participation in a registry and long-term follow-up services. Eligibility for Early Check extends to newborns up to one month of age, and the program utilizes the existing dry blood spots collected by the newborn screening system.

Progress and Plans for Angelman Syndrome Screening

The Early Check program is working with David Godler in Australia, who developed an assay for Angelman syndrome several years ago. This methylation-based assay has been tested on thousands of de-identified newborn dry blood spot specimens. However, Early Check is unique in that it aims to use the assay for prospective screening, reporting results to families, and providing follow-up services. The program is currently validating the assay in their CLIA laboratory, developing confirmatory testing and follow-up protocols, and updating all Early Check materials to reflect screening for Angelman syndrome.

Conclusion and Contact Information

The Early Check program in North Carolina is making significant progress in implementing newborn screening for various conditions, including Angelman syndrome. The program’s collaborative efforts, comprehensive approach, and dedication to newborn screening work are driving its success. For more information or to contact the Early Check team, reach out to Katerina Kucera or Anne Wheeler, who lead different aspects of the program.