OasisLMS

Biochemical/Metabolic and Therapeutics

Section Total 7.5

Do Not Miss Treatable Inborn Errors of Metabolism

1.5

False Positives in Biochemical Genetics: Challenges and Cautionary Tales

1.5

Platform 2 - Biochemical/Metabolic

1.5

Platform 7 - Biochemical/Metabolic

1.5

When The Trial Ends Early: Perspectives on Premature Clinical Trial Closures in Rare Disease Therapeutics
ACMG-Designated Ethics Credit

1.5

Cancer Genetics and Therapeutics

Section Total 7.5

Clonal Hematopoiesis, Somatic and Post-Zygotic Mosaicism in Multigene Cancer Testing for Geneticists

1.5

Medical Diagnostic Challenges (Adult and Cancer)

1.5

Platform 1- Hereditary Cancer and Adult Genetics

1.5

Platform 6 - Cancer and Aneuploidy

1.5

The New Era of Genomic Oncology: Technology, Complexity, and Clinical Impact

1.5

Clinical Genetics and Therapeutics

Section Total 14.5

Beyond The List – Scope and Implementation of ACMG Secondary Findings
ACMG-Designated Ethics Credit

1.5

Bridging Diagnosis and Therapy: The Expanding Role of Somatic Testing in Vascular Anomalies

1.5

Cardinal Signs

1.5

Diagnostic Dilemmas from the Undiagnosed Diseases Network

1.5

Early Genetics Trainee Forum: Mastering the Challenges of Diagnosing and Managing Overgrowth, Connective Tissue, and Mitochondrial Disorders

1.5

Featured Platform Presentations

1

Gene Therapy in Action: Real-World Implementation in Clinical Genetics

1.5

Platform 3 - Integrative Genomics and Translational Discovery

1.5

Platform 4 - Genomic Analysis Tools and Workforce

1.5

Polygenic Scores and Embryo Screening: Navigating the Clinical and Ethical Applications
ACMG-Designated Ethics Credit

1.5

Education and Research Strategies

Section Total 4.5

Demystifying Neurology in Genetic Diagnosis: A Practical Approach for Geneticists

1.5

Leading the Field, Coming Out in Front

1.5

Uniting Science, Standards, and Policy: Collaborative Approaches for Accelerating Pharmacogenomics Adoption

1.5

Ethical, Legal, Social Issues (ELSI), Public Health and Policy

Section Total 1.5

Hot Topics in Washington, DC and Impacts to Medical Genetics

1.5

Health Services and Implementation

Section Total 7.0

• 2026 ACMG Presidential Plenary Session- The Future of Expanded Newborn Genomic Screening: Promise and Practice
• Late Breaking Open Forum: Expanded Newborn Genomic Screening—What’s Next?

2.5

Beyond the Genetics Clinic: Frontline Perspectives on Integrating Genomics in Specialty Care

1.5

R. Rodney Howell Symposium - Delivering Pharmacogenomics at Scale: Implementation Strategies That Work

2

Ted-Style Talks: Advancing Genomics Engagement

1

Laboratory Genetics and Genomics

Section Total 14.0

Advances in Genomics with AI: From Patient Selection to Variant Analysis and Beyond
ACMG-Designated Ethics Credit

1.5

Beyond Uncertainty: Using Functional Assays for Clinical Variant Classification

2

Dilemmas of Omic Technologies for Molecular Diagnosis of Rare Disease
ACMG-Designated Ethics Credit

1.5

Genetic Counselor Forum - Consanguinity: Counseling, Laboratory and Ethical Considerations in the Genomic Era
ACMG-Designated Ethics Credit

1.5

Laboratory Diagnostic Challenges: Constitutional and Neoplastic Cases in Molecular, Cytogenomic, and Biochemical Genetics Specialties

1.5

Platform 5 - New Laboratory Techniches (Long read, OGM, RNA, PRS)

1.5

Platform 8 - Rapid WGS and Newborn Screening

1.5

Rewriting the Reference: Laboratory and Clinical Applications of the New Human Pangenome Reference

1.5

The Laws of the Ring: Diagnostic Algorithm, Formation Mechanisms, and Clinical Consequences

1.5

Prenatal Genetics

Section Hours 4.5

Challenge the Experts - Pediatric and Prenatal Diagnostic Dilemmas (rare knowns and unknowns)

1.5

Non-invasive fetal sequencing (NIFS) is coming: Are you ready?

1.5

Reproductive Carrier Screening: Is It Time for Whole Genome Testing?

1.5

Total Accredited Educational Hours

61

Biochemical/Metabolic and Therapeutics

Do Not Miss Treatable Inborn Errors of Metabolism

Inborn errors of metabolism (IEMs) are a group of rare genetic disorders that result from defects in enzymes or transporters involved in metabolism. Some IEMs present with subtle or atypical clinical features and can be challenging to diagnose. Traditional newborn screening (NBS) programs can detect many metabolic disorders, but it is not comprehensive and misses some treatable IEMs. Also, many IEMs can first present in adulthood with symptoms that may be misdiagnosed. Thus, many patients with treatable IEMs suffer from delayed or inappropriate treatments, leading to unnecessary morbidity or mortality.

This session will address key challenges in diagnosing IEMs in patients with normal NBS results, atypical presentations in adults, and red flags in laboratory, physical exam and imaging findings that may suggest an undiagnosed IEM. By providing in-depth knowledge of these topics, this session will help clinicians to identify and manage patients with IEMs more effectively, improving patient outcomes through timely diagnosis and treatment.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Recognize both common and atypical adult presentations of inborn errors of metabolism (IEMs), including signs that may mimic other disorders, and understand that dysmorphic features or congenital anomalies do not rule out IEMs.
• Interpret laboratory and imaging findings to identify red flags for potential IEMs, and evaluate the limitations of newborn screening in detecting treatable metabolic conditions.
• Implement a systematic diagnostic approach for IEMs to facilitate timely identification, appropriate management, and improved patient outcomes.

Presentations

• Welcome and Overview
  Nicholas Ah Mew, MD, FACMG
• Do Not Miss Adult IEM Disorders
  Kimberly A. Chapman, MD, PhD, FACMG
• Do Not Miss IEM Disorders with Physical or Radiological Clues
  Carlos R. Ferreira, MD, FACMG
• Do Not Miss General Laboratory Clues for IEMs
  Kevin E. Glinton, MD, PhD, FACMG
• Treatable IEMs Missed by Newborn Metabolic Screen
  Kristen E. Murphey, MD, FACMG
  Emory University School of Medicine
• Panel Discussion and Q&A

False Positives in Biochemical Genetics: Challenges and Cautionary Tales

Biochemical genetics (BCG) laboratory testing plays a crucial role in diagnosing inborn errors of metabolism (IEM). However, false positive results can lead to unnecessary anxiety, further investigations, and potential. This proposal from the SIMD Education Committee and ClinGen Pseudodeficiency Working Group outlines sessions for clinical and laboratory professionals addressing these challenges. It emphasizes how diets, supplements, and medications can cause falsely abnormal results that impact patient management. In newborn screening labs, factors like maternal contributions and therapeutic interventions may also skew outcomes. The third session will also raise awareness to false positives seen in patients with different general genetics conditions. The last session will discuss evolving concepts of pseudodeficiencies, underscoring the need for precise understanding and genetic counseling.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Describe the challenges and clinical implications of false-positive results in biochemical and newborn screening laboratories.
• Identify laboratory values and genetic conditions (including pseudodeficiency) that can lead to false-positive findings.
• Explain how evolving concepts in biochemical genetics influence the interpretation of enzyme activity and screening outcomes.

Presentations

• Welcome and Overview
  Andrea L. Gropman, MD, FACMG
• Unexpected Influencers: Impact of Diets and Medications on Biochemical Genetic Testing
  Tatiana Yuzyuk, PhD, FACMG
• Blurring the Lines: The Intersection of Genetic and Metabolic Pathways in Disease
  Brian J. Shayota, MD, MPH, FACMG
• The Newborn Period: Metabolic Testing Interferences and Pitfalls
  Chunli Yu, MD, FACMG
• False Positives, True Origins: The Genetic Confounders in BCG Tests
  Catherine W. Rehder, PhD, FACMG
• Panel Discussion and Q&A

Platform 2 - Biochemical/Metabolic

Platform presentations represent the highest-ranking abstract submissions, selected by the Abstract Review Committee for oral presentation. Each platform presentation consists of a 13-minute presentation followed by a 2-minute question-and-answer period.

O02 - Survival, Clinical, and Biomarker Data Support the Efficacy of Intrathecal Adrabetadex in Niemann-Pick Disease Type C
O05 - Defining the Genotype-CRIM Status Relationship in a Large Cohort of 215 Patients With Infantile-onset Pompe Disease
O07 - Inhibiting Wnt/ß-catenin-mTOR Signaling Enhances Porphyrin Clearance in Porphyrias with Hepatic Involvement
O06 - Multi-Omic Evaluation of Glycosylation Restoration Therapy in SLC35A2-CDG
O09 - Sepiapterin Responsiveness Over 14 Days in Children and Adults With Phenylketonuria: Pooled Results From Three Phase 3 Clinical Trials
O63 - Reproductive Carrier Screening for Metabolic Conditions With Heterozygous Manifestations

Learning Objectives
At the conclusion of this session, participants should be able to:

• Apply biochemical and molecular findings to clinical diagnosis and treatment planning
• Integrate therapeutic response data into patient monitoring strategies
• Adjust clinical management based on evolving metabolic and genomic evidence

Presentations

• Matthew A. Deardorff, MD, PhD, FACMG
• Ecenur Tuc Bengur, MD
• Survival, Clinical, and Biomarker Data Support the Efficacy of Intrathecal Adrabetadex in Niemann-Pick Disease Type C
  Elizabeth M. Berry-Kravis, MD, PhD
  Rush University Medical Center, Chicago
• Defining the Genotype–CRIM Status Relationship in a Large Cohort of 215 Patients with Infantile-Onset Pompe Disease
  Parisa Amirifar, PhD
• Inhibiting Wnt/β-catenin-mTOR Signaling Enhances Porphyrin Clearance in Porphyrias with Hepatic Involvement
  Oluwashanu Balogun, PhD, MS
  Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh
• Multi-Omic Evaluation of Glycosylation Restoration Therapy in SLC35A2-CDG
  Andrew C. Edmondson, MD, PhD, FACMG
• Sepiapterin Responsiveness Over 14 Days in Children and Adults with Phenylketonuria: Pooled Results from Three Phase 3 Clinical Trials
  Melissa D. Lah, MD, FACMG
• Reproductive Carrier Screening for Metabolic Conditions with Heterozygous Manifestations
  Christian M. Parobek, MD, PhD

Platform 7 - Biochemical/Metabolic

Platform presentations represent the highest-ranking abstract submissions, selected by the Abstract Review Committee for oral presentation. Each platform presentation consists of a 13-minute presentation followed by a 2-minute question-and-answer period.

O25 - Treatment for AD Disorders: Amplifying Protein Expression With Gene-specific Antisense Oligonucleotides Targeting a Common 3'UTR Motif
O04 - Growth Outcomes and Safety of Navepegritide in Children With Achondroplasia: Results of the ApproaCH Trial Open Label Extension
O03 - Mitochondrial Function in Fibroblasts From a Patient With Congenital NAD Deficiency Due to Biallelic NADSYN1 Variants
O22 - A Novel Clinical-Translational Model of Leukoencephalopathy with Calcifications and Cysts Recapitulates the Human Phenotype
O08 - Re-evaluation of Genotype-Phenotype Correlations in D-Bifunctional Protein Deficiency in a Phenotypically Diverse Cohort of 27 Natural History Study Participants
O10 - Evaluating the Role of Mitochondrial Dysfunction in Muscle Cell Differentiation in an iPSC-derived Skeletal Muscle Model of Barth Syndrome

Learning Objectives
At the conclusion of this session, participants should be able to:

• Apply translational research findings to metabolic disease management
• Integrate genotype–phenotype data into clinical decision-making
• Adjust patient care strategies based on functional and molecular insights

Presentations

• Shivarajan Manickavasagam Amudhavalli, MBBS, MD, FACMG
• Nadav I. Weinstock, MD, PhD
• Treatment for AD Disorders: Amplifying Protein Expression with Gene-Specific Antisense Oligonucleotides Targeting a Common 3'UTR Motif
  Benjamin D. Boros, PhD
• Growth Outcomes and Safety of Navepegritide in Children with Achondroplasia: Results of the ApproaCH Trial Open-Label Extension
  Ravi Savarirayan
• Mitochondrial Function in Fibroblasts from a Patient with Congenital NAD Deficiency Due to Biallelic NADSYN1 Variants
  Bianca Seminotti, PhD, MS
• A Novel Clinical-Translational Model of Leukoencephalopathy with Calcifications and Cysts Recapitulates the Human Phenotype
  Brianna R. Pierce
• Re-evaluation of Genotype–Phenotype Correlations in D-Bifunctional Protein Deficiency in a Phenotypically Diverse Cohort of 27 Natural History Study Participants
  Roan Blakeley
• Evaluating the Role of Mitochondrial Dysfunction in Muscle Cell Differentiation in an iPSC-Derived Skeletal Muscle Model of Barth Syndrome
  Valeria A. Silva

When The Trial Ends Early: Perspectives on Premature Clinical Trial Closures in Rare Disease Therapeutics
Medical genetics has entered a new therapeutic era, with increasing FDA approvals for rare disease treatments such as pegvaliase, vosoritide, and Skysona. Alongside this growth, numerous clinical trials have launched, but many have ended prematurely—often due to funding issues—despite showing promise. These disruptions leave patients without treatment guidance and clinicians without solutions. This session will explore the human and systemic impact of early trial closures. Mr. Jackson Fukuda, a patient and advocate, will share the emotional toll on families. Dr. Markey McNutt will discuss the investigator perspective. Dr. Joseph Muenzer will address the regulatory and financial hurdles to drug approval for ultra-rare conditions. Dr. Melinda Peters will offer a regulatory view on the complex aftermath of abruptly halted trials.

Together, these perspectives highlight the need for sustainable, ethical frameworks to advance therapeutics in rare disease care.
ACMG-Designated Ethics Credit

Learning Objectives
At the conclusion of this session, participants should be able to:

• Describe the evolution of therapeutic development in medical genetics and its impact on rare disease management.
• Identify the regulatory, ethical, and practical challenges posed by premature clinical trial terminations.
• Discuss the psychological and clinical consequences of early trial closure on affected patients and families.
• Evaluate potential strategies for maintaining patient care continuity when investigational therapies are halted.

Presentations

• Welcome and Overview
  Julie M. Porter, MD, PhD, FACMG
• Hope Interrupted: The Emotional Cost to Families in Discontinued Clinical Trials
  Jackson Fukuda
• When the Funding Stops: Navigating Trial Disruption and Its Impact on Families and Investigators
  Markey McNutt, MD, PhD, FACMG
• The Challenges of FDA Approval for Promising Products for Rare Disorders
  Joseph Muenzer, MD, PhD
• Regulatory Aftershocks: Navigating the Fallout of Abrupt Clinical Trial Closures
  Melinda Peters, MD
• Panel Discussion and Q&A

Cancer Genetics and Therapeutics

Clonal Hematopoiesis, Somatic and Post-Zygotic Mosaicism in Multigene Cancer Testing for Geneticists

Description
Recognition of acquired pathogenic variants (PVs), usually associated with clonal hematopoiesis (CH), highlights the importance of distinguishing true germline/constitutional PVs (including post-zygotic mosaicism of one or more embryonic layers, or “true mosaicism”) from entirely somatic acquired events that may or may not be associated with the development of neoplasia.

In this session, thought leaders in oncogenetics and hematologic malignancy will address gaps in diagnosing and understanding likely somatic PVs, such as TP53-associated variants with aberrant clonal expansion. The session will also explore evidence for involvement of other breast cancer genes, including CHEK2 and ATM, in clonal hematopoiesis; recent insights into somatic and post-zygotic mosaicism of NF1; APC whole-gene deletions as a manifestation of 5q deletion-associated myelodysplastic syndrome rather than familial polyposis; and the expanding catalog of genes associated with inherited hematologic neoplasms.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Evaluate the importance of phenotype when examining low allele fraction pathogenic variants (PVs) in syndromic genes
• Differentiate between somatic and germline PVs to identify potential mosaicism
• Examine factors associated with clonal hematopoiesis and the development of hematologic malignancies

Presentations

• Welcome and Overview
  Jeffrey N. Weitzel, MD, FACMG
• APC/5q Deletion and TP53-Driven Clonal Hematopoiesis Masquerading as FAP and LFS
  Jeffrey N. Weitzel, MD, FACMG
• A Genotype-First Approach to Breaking Down NF1 PVs With Distinct Disease Associations, Mosaicism, and Cancer Risk
  Theodore G. Drivas, MD, PhD, FACMG
• Likely Somatic PVs in Cancer Genes Detected by Multigene Panel Testing Among Population-Based Cohorts and Diagnostic Laboratories
  Nicholas Boddicker
• What We Learned About Clonal Hematopoiesis from Paired Tumor and Germline Cancer Gene Sequencing
  Kelly Bolton
• Panel Discussion and Q&A

Medical Diagnostic Challenges (Adult and Cancer)

Description
This session provides attendees with an opportunity to present cases to a panel of experts and an audience of geneticists for discussion of differential diagnosis, treatment, and counseling options in adult patients with genetic disorders. The format encourages lively interaction between the audience and panel as each case is presented.

All types of cases are eligible, including neurogenetic, metabolic, cancer, connective tissue, cardiac, ethical dilemmas, and counseling-related cases. Cases may be unknown diagnoses, rare known diagnoses, or patients with clinically uncharacterized or incompletely characterized variants of uncertain significance (VUS). Each presentation is limited to five slides and includes 10 minutes for presentation and discussion with the audience and panelists.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Present and analyze clinical cases from chief complaint to final diagnosis
• Develop and contribute to differential diagnoses while recognizing key clinical features, including rare presentations
• Evaluate and review diagnostic workups in light of expert recommendations

Presentations

• Welcome and Introduction
  Huma Q. Rana, MD, FACMG
• Case 1
  John Pina, DO
• Case 2
  Haslina Hashim
• Case 3
  Alison S. Levine
• Case 5
  Eirini Christodoulou, PhD, MS
• Case 6
  Ruba Abdul Wahed
• Case 7
  Madhulatha Pantrangi, PhD, FACMG
• Wrap-Up and Closing Remarks
  Jaime Vengoechea, MD, FACMG

Platform 1- Hereditary Cancer and Adult Genetics

Description
Platform presentations represent the highest-ranking abstract submissions, selected by the Abstract Review Committee for oral presentation. Each platform presentation consists of a 13-minute presentation followed by a 2-minute question-and-answer period.

• O12 – Comprehensive Pan-Cancer Assessment of the APC I1307K Variant Reveals Ancestry-Independent Colorectal Cancer Risk
• O15 – Cancer Phenotypes of Hypomorphic Versus Non-Functional TP53 Variants in Li-Fraumeni Syndrome
• O13 – Prevalence of Cancer Predisposition Variants in a Pediatric Pineoblastoma Cohort
• O16 – Expanded Germline Cancer Predisposition Testing Increases Diagnostic Yield Across Cancer Types
• O28 – Hidden Genetic Risk: Unanticipated Indications for Testing in an Adult Genomic Health Clinic
• O43 – High Diagnostic Yield, Unequal Access, and Emerging Guidelines in Adult Genetics: Results and Insights From an 8-Year, 7,000-Patient Analysis

Learning Objectives
At the conclusion of this session, participants should be able to:

• Incorporate germline cancer risk data into patient counseling and management
• Refine risk assessment strategies based on genotype–phenotype correlations
• Implement evidence-based recommendations for testing and follow-up

Presentations

• Pongtawat Lertwilaiwittaya, MD, FACMG
• Maxwell Summerlin, MD, FACMG
• Comprehensive Pan-Cancer Assessment of the APC I1307K Variant Reveals Ancestry-Independent Colorectal Cancer Risk
  Maksym Misyura, PhD, FACMG
• Cancer Phenotypes of Hypomorphic Versus Non-Functional TP53 Variants in Li-Fraumeni Syndrome
  Alison S. Levine
• Prevalence of Cancer Predisposition Variants in a Pediatric Pineoblastoma Cohort
  Fang Fang, PhD
• Expanded Germline Cancer Predisposition Testing Increases Diagnostic Yield Across Cancer Types
  Qiliang Ding, PhD, MS
• Hidden Genetic Risk: Unanticipated Indications for Testing in an Adult Genomic Health Clinic
  Danielle R. Hoffman, MS, CGC
• High Diagnostic Yield, Unequal Access, and Emerging Guidelines in Adult Genetics: Results and Insights From an 8-Year, 7,000-Patient Analysis
  Theodore G. Drivas, MD, PhD, FACMG

Platform 6 - Cancer and Aneuploidy

Description
Platform presentations represent the highest-ranking abstract submissions, selected by the Abstract Review Committee for oral presentation. Each platform presentation consists of a 13-minute presentation followed by a 2-minute question-and-answer period.

• O14 – Improving Detection of Variant MECOM Rearrangements Through Optical Genome Mapping and Repurposed Targeted RNA-Seq
• O51 – The Co-occurring Cytogenetic Landscape in Pediatric t(12;21)(p13;q22)/ETV6::RUNX1-Positive Acute Lymphoblastic Leukemia
• O36 – Optical Genome Mapping for Cytogenetic Analysis in Multiple Myeloma: Real-World Evidence
• P066 – Integrating Tumor-Normal Testing to Clarify the Significance of Adult-Onset Cancer Predisposition Genes in Pediatric Cancer Patients
• O34 – A Single-Center Review of Survival and Clinical Phenotype Among Children With Trisomy 18 and 13
• O23 – Network for Advancing Sex Chromosome Aneuploidy Research Readiness (NASCARR): A New Consortium of the Rare Disease Clinical Research Network (RDCRN)

Learning Objectives
At the conclusion of this session, participants should be able to:

• Incorporate cytogenetic and genomic findings into cancer risk assessment and care
• Modify diagnostic strategies based on multi-omic and cytogenetic data
• Implement evidence-based approaches to cancer and aneuploidy evaluation

Presentations

• Yang Cao, PhD, FACMG
• Reger Mikaeel, PhD, MS
• Improving Detection of Variant MECOM Rearrangements Through Optical Genome Mapping and Repurposed Targeted RNA-Seq
  Paige Van Haute
• The Co-occurring Cytogenetic Landscape in Pediatric t(12;21)(p13;q22)/ETV6::RUNX1-Positive Acute Lymphoblastic Leukemia
  Andrew Miller, PhD
• Optical Genome Mapping for Cytogenetic Analysis in Multiple Myeloma: Real-World Evidence
  Sichen Liang, MD
• Integrating Tumor-Normal Testing to Clarify the Significance of Adult-Onset Cancer Predisposition Genes in Pediatric Cancer Patients
  Mohammad K. Eldomery, MBBS
• A Single-Center Review of Survival and Clinical Phenotype Among Children With Trisomy 18 and 13
  Sara Elizabeth Tsimerman, MD
• Network for Advancing Sex Chromosome Aneuploidy Research Readiness (NASCARR): A New Consortium of the Rare Disease Clinical Research Network (RDCRN)
  Susan Howell, MGC, MBA

The New Era of Genomic Oncology: Technology, Complexity, and Clinical Impact

Description
Genomic oncology is rapidly evolving, driven by powerful new technologies that promise to transform cancer care. This future-focused session will explore four key pillars shaping the next era: AI-enabled analytics, liquid biopsies, multi-omic integration, and optical genome mapping. While these tools offer immense potential for earlier detection, precise classification, and targeted treatment, their clinical adoption remains uneven.

Experts will discuss the promise and limitations of each approach, highlighting what it will take to move from innovation to real-world implementation and how these advances can ultimately improve patient outcomes.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Describe the emerging roles of AI-enabled analytics, liquid biopsies, multi-omic integration, and optical genome mapping in cancer diagnostics
• Evaluate the clinical utility, limitations, and interpretive challenges associated with each of these technologies
• Assess the current state of adoption and readiness across institutions, including barriers related to infrastructure, workforce, and standardization

Presentations

• Welcome and Overview
  Panieh Terraf, PhD, FACMG
• Novel Approaches to Cancer Profiling and Treatment Response Prediction Using Cell-Free DNA
  Aadel Chaudhuri
• Automated Real-World Data Integration Improves Cancer Diagnosis and Outcome Prediction
  Nikolaus Schultz, PhD
• Multi-Omic Genomes as a Uniting Force for Cancer Detection, Diagnostics, and Monitoring
  Trevor J. Pugh, PhD, FACMG
• Optical Genome Mapping in Cancer: Bridging Cytogenetics and Molecular Genomics
  Yassmine Akkari, PhD, FACMG
• Panel Discussion and Q&A

Clinical Genetics and Therapeutics

Beyond The List – Scope and Implementation of ACMG Secondary Findings

Description
The session will begin with a brief overview of the history of the ACMG Secondary Findings (SF) Working Group, including published recommendations for the inclusion of gene–disease pairs and reporting of secondary findings. We will describe the evolution of the SF list, which is now more than 50% larger than when it was first introduced.

This session will extend beyond specific gene–disease pairs on the ACMG Secondary Findings list to explore the guiding principles that shape its scope. Presentations will address practical aspects of implementing secondary genomic screening and examine implications and challenges from the perspectives of laboratory geneticists, clinical geneticists, genetic counselors, and patients.

Following the presentations, the panel will discuss future goals for the ACMG SF Working Group to meet the evolving needs of secondary genomic screening.

ACMG-Designated Ethics Credit

Learning Objectives
At the conclusion of this session, participants should be able to:

• Analyze factors influencing the selection of gene–disease pairs for the ACMG SF list, including phenotypic features, technical considerations, and perspectives on actionability
• Interpret current clinical research and evidence on returning secondary findings, including impacts on patient outcomes, health system implementation, and challenges beyond the current ACMG SF list
• Evaluate ethical considerations of returning ACMG secondary findings, particularly in the context of emerging therapies such as nucleic acid–based treatments

Presentations

• Welcome and Overview
  David T. Miller, MD, PhD, FACMG
• The Clinical Laboratory Stakeholder Perspective on ACMG Secondary Findings
  Heidi L. Rehm, PhD, FACMG
• Clinical Implementation of ACMG Secondary Findings
  Yvonne Bombard, PhD
• Ethical Considerations in Returning ACMG Secondary Findings: Balancing Utility, Responsibility, and Choice
  Kyle B. Brothers, MD, PhD
• Panel Discussion and Q&A

Bridging Diagnosis and Therapy: The Expanding Role of Somatic Testing in Vascular Anomalies

Description
Precise diagnosis of vascular anomalies has become increasingly important with the rise of therapies targeting their genetic basis. However, standard testing often fails to detect low-frequency somatic variants, making invasive tissue biopsies a common—yet challenging—approach. Somatic testing practices remain variable, and the burden of invasive sampling affects both families and providers.

Advances in sequencing technologies, particularly cell-free DNA (cfDNA) and affected tissue analysis, have enabled the identification of variants in PI3K/AKT/mTOR and Ras/MAPK pathways, revealing actionable genotype–phenotype correlations. This session will examine evolving diagnostic strategies and highlight therapeutic opportunities, including off-label use of agents such as sirolimus, alpelisib, and MEK inhibitors.

Presentations will cover the molecular basis of vascular anomalies, advances in somatic testing, and the clinical translation of genomic data into targeted treatments, offering a comprehensive view of this rapidly advancing field.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Describe the clinical and molecular heterogeneity of vascular anomalies and the pathways involved in their pathogenesis
• Evaluate current genetic and somatic testing methodologies, including cfDNA-based approaches, and apply them to appropriate clinical scenarios while considering ethical and practical challenges
• Interpret somatic genotype data to guide therapeutic decisions, including the potential off-label use of targeted agents

Presentations

• Welcome and Overview
  Aisha N. Rekab, MS
• Introduction to Vascular Anomalies and Molecular Pathways
  Matthew A. Deardorff, MD, PhD, FACMG
• Genetic Testing Methodologies in Vascular Anomalies
  James T. Bennett, MD, PhD, FACMG
• Genomics Informs Precision Medicine for Vascular Malformations
  Sarah E. Sheppard, MD, PhD, FACMG
• MEK Inhibitors: What They Are and Why They Matter in Vascular Anomalies
  Joyce Teng, MD
• Panel Discussion and Q&A

Cardinal Signs

Description
The important clinical manifestations (“cardinal signs”) of four disorders encountered by clinical geneticists will be discussed, including the natural progression of each condition, disorders with overlapping features that may mimic these conditions, and their underlying causes (and available treatments, when applicable).

Learning Objectives
At the conclusion of this session, participants should be able to:

• Identify distinctive craniofacial features of specific syndromes, including Shashi-Pena and Kaufman oculocerebrofacial syndromes
• Recognize the clinical variability and diagnostic considerations for Baraitser-Winter syndrome
• Compare management approaches for syndromic craniofacial conditions, such as Treacher Collins syndrome versus other forms of syndromic micrognathia

Presentations

• Welcome and Overview
  Lynne M. Bird, MD, FACMG
  University of California San Diego
• Kaufman Oculocerebrofacial Syndrome
  Kristen N. Wigby, MD, FACMG
• A Guide to the Clinical Recognition of Shashi-Pena Syndrome
  Vandana Shashi, MBBS, FACMG
• Baraitser-Winter Syndrome: Two Genes, Many Phenotypes
  Anne L. Slavotinek, MBBS, PhD, FACMG
• Treacher Collins Syndrome
  Tara L. Wenger, MD, PhD, FACMG
• Panel Discussion and Q&A

Diagnostic Dilemmas from the Undiagnosed Diseases Network

Description
This session will highlight complex diagnostic cases from the Undiagnosed Diseases Network (UDN). Expert clinicians will present detailed case summaries of patients who have defied conventional diagnostic approaches. Attendees will gain insight into the multidisciplinary strategies employed by the UDN and will have the opportunity to contribute ideas for additional diagnostic avenues.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Analyze the complexities and challenges in diagnosing rare and undiagnosed diseases, including identifying appropriate cases for submission to the UDN
• Evaluate multidisciplinary strategies and advanced technologies employed by the UDN to address complex diagnostic dilemmas
• Apply knowledge of medical genetics, innovative methodologies, and collaborative approaches to enhance competence in solving challenging diagnostic cases

Presentations

• Welcome and Overview
  Thomas Cassini, MD, FACMG
• Case 1 – Pediatrics Case
  Anne L. Slavotinek, MBBS, PhD, FACMG
• Case 2 – Adult Case
  Kathleen A. Leppig, MD, FACMG
• Case 3 – Pediatrics Case
  Ellen F. Macnamara, MMSc
• Case 4 – Adult Case
  Jill A. Rosenfeld, MS
• Case 5 – Adult Case
  Thomas Cassini, MD, FACMG
• Panel Discussion and Q&A

Early Genetics Trainee Forum: Mastering the Challenges of Diagnosing and Managing Overgrowth, Connective Tissue, and Mitochondrial Disorders

Description
Complex genetic conditions—such as mitochondrial disorders, connective tissue diseases, and overgrowth syndromes—can be challenging and often feel intimidating to early-career genetics professionals. These cases frequently lack clear diagnostic pathways or standardized treatment guidelines, leaving clinicians uncertain about diagnostic approaches, the extent of evaluation, and appropriate management strategies.

This session brings together specialists with deep expertise in these areas to share practical insights, decision-making frameworks, and real-world approaches. By learning directly from experts who routinely navigate these complexities, trainees and recent graduates will gain tools to approach difficult cases with greater confidence, clarity, and effectiveness in both diagnosis and management.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Identify key clinical, imaging, and laboratory findings, and outline appropriate evaluations and sample types that support genetic diagnoses, including overgrowth syndromes
• Apply published diagnostic criteria to recognize connective tissue disorders such as hypermobile Ehlers-Danlos syndrome and Marfan syndrome
• Formulate treatment approaches for genetic conditions, including mitochondrial disorders, using shared decision-making strategies

Presentations

• Welcome and Overview
  Lauren Thompson, DO, FACMG
• Optimizing Diagnostic Approaches in Overgrowth Syndromes: Evaluations and Sample Selection
  Julie A. Neidich, MD, FACMG
• Making the Diagnosis: Using Established Criteria in Connective Tissue Disorders
  Harry Dietz, MD
• Treating Mitochondrial Disorders: The Role of the Mitochondrial Cocktail
  Austin Larson, MD
• Panel Discussion and Q&A

Featured Platform Presentations

Description
Platform presentations represent the highest-ranking abstract submissions, selected by the Abstract Review Committee for oral presentation. Each platform presentation consists of a 13-minute presentation followed by a 2-minute question-and-answer period.

• O37 – Demystifying Base Large Language Model: Reproducibility and Accuracy in ACMG/AMP Variant Classification
• O18 – Deciphering DHX9 Gene Pathogenicity in Neurological Disorders with Distinct Phenotypes
• O01 – Clinical Efficacy and Safety Data in Adolescents Treated with Repinatrabit for Phenylketonuria
• O11 – Prevalence and Tumor Characteristics of Patients with TMEM127 Pathogenic Variants in a Large, Pan-Cancer Cohort

Learning Objectives
At the conclusion of this session, participants should be able to:

• Incorporate emerging genomic evidence into clinical and laboratory practice decisions
• Modify practice approaches based on new efficacy, safety, or methodological data
• Implement updated interpretation strategies that reflect current research findings

Presentations

• Nathan D. Kopp, PhD, FACMG
• Demystifying Base Large Language Model: Reproducibility and Accuracy in ACMG/AMP Variant Classification
  Zhiyv Niu, PhD, FACMG
• Deciphering DHX9 Gene Pathogenicity in Neurological Disorders with Distinct Phenotypes
  Shen Gu, PhD, FACMG
• Clinical Efficacy and Safety Data in Adolescents Treated with Repinatrabit for Phenylketonuria
  Markey McNutt, MD, PhD, FACMG
• Prevalence and Tumor Characteristics of Patients with TMEM127 Pathogenic Variants in a Large, Pan-Cancer Cohort
  Eva Vailionis

Gene Therapy in Action: Real-World Implementation in Clinical Genetics

Description
Gene therapies represent a transformative class of treatments that work by modifying genetic material through transcription, translation, or genomic integration. Since the discovery of the transforming principle in 1928, the field has evolved dramatically—culminating in recent FDA approvals such as eladocagene exuparvovec for AADC deficiency.

Despite this progress, integrating gene therapy into clinical practice remains complex. This session will explore key steps in implementation, including therapy selection, pharmacy readiness, team leadership, and post-marketing surveillance. Presentations will address practical considerations for delivering gene therapies and preparing the workforce and infrastructure needed to support this rapidly advancing field.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Describe the current landscape, clinical indications, and post-marketing safety considerations of FDA-approved gene therapies
• Identify pharmacy requirements for the safe handling, preparation, and administration of gene therapy products
• Outline the clinician’s role in coordinating multidisciplinary gene therapy care, including approval processes, administration, follow-up, and adverse event reporting

Presentations

• Welcome and Overview
  Andres A. Morales Corado, MD, FACMG
• Setting Up Your Pharmacy to Be Gene Therapy Ready
  Hyun Kim, PharmD
• A Clinician’s Task in Leading a Gene Therapy Team: A Geneticist Perspective
  Carlos E. Prada, MD, FACMG
• Gene Therapies and Post-Marketing Approval Monitoring
  Rebecca C. Ahrens-Nicklas, MD, PhD, FACMG
• A Clinician’s Task in Leading a Gene Therapy Team: A Neurologist Perspective
  Russell J. Butterfield, MD, PhD
• Panel Discussion and Q&A

Platform 3 - Integrative Genomics and Translational Discovery

Description
Platform presentations represent the highest-ranking abstract submissions, selected by the Abstract Review Committee for oral presentation. Each platform presentation consists of a 13-minute presentation followed by a 2-minute question-and-answer period.

• O30 – GATAD2B-Associated Neurodevelopmental Disorder (GAND): Clinical Insights and Investigations With Animal and Human Cellular Models of NuRDopathies
• O39 – Genome x Environment Analysis of Sudden Unexpected Infant Death Unveils Etiologic Heterogeneity and Strong Cannabis and Genetic Disease Risks
• O44 – Pharmacogenomics Standardization to Promote Global Uptake
• O64 – Genomic and Functional Dissection of Fetal Brain Abnormalities
• O59 – Combined Donor and Immune Cell-Free DNA Signatures to Enhance Accurate Detection of Cardiac Allograft Rejection
• O56 – Enhanced Genomic and Prognostic Understanding of Thoracic Aortic Aneurysms/Dissections (TAAD): A Study of 1,340 Early-Onset Patients With Extended Follow-Up

Learning Objectives
At the conclusion of this session, participants should be able to:

• Interpret multi-omic data to support translational research and clinical insight
• Assess gene–environment and functional evidence in complex disease models
• Apply integrative approaches to advance genomic discovery and application

Presentations

• Jodi D. Hoffman, MD, FACMG
• Randall Ray, MD
• GATAD2B-Associated Neurodevelopmental Disorder (GAND): Clinical Insights and Investigations With Animal and Human Cellular Models of NuRDopathies
  Tyler M. Pierson, MD, PhD
  Guerin Children’s, Department of Pediatrics
• Genome x Environment Analysis of Sudden Unexpected Infant Death Unveils Etiologic Heterogeneity and Strong Cannabis and Genetic Disease Risks
  Daniel C. Helbling, MS
• Pharmacogenomics Standardization to Promote Global Uptake
  Victoria Cancelliere, PharmD, BCPS
• Genomic and Functional Dissection of Fetal Brain Abnormalities
  Andrea Johnson, MS
• Combined Donor and Immune Cell-Free DNA Signatures to Enhance Accurate Detection of Cardiac Allograft Rejection
  Temesgen Andargie, PhD, MS
• Enhanced Genomic and Prognostic Understanding of Thoracic Aortic Aneurysms/Dissections (TAAD): A Study of 1,340 Early-Onset Patients With Extended Follow-Up
  Meng Su, PhD, FACMG

Platform 4 - Genomic Analysis Tools and Workforce

Description
Platform presentations represent the highest-ranking abstract submissions, selected by the Abstract Review Committee for oral presentation. Each platform presentation consists of a 13-minute presentation followed by a 2-minute question-and-answer period.

• O24 – STELLAR-AIM: State-of-the-Art Genetic Differential Diagnosis by AI Using Knowledge Extraction From Literature and Metabolomic, Genomic, and Phenotypic Data
• O60 – A Semi-Quantitative Framework Curating Mechanism of Pathogenicity in Monogenic Conditions: A Consensus Effort of the Gene Curation Coalition
• O57 – The AnVIL Clinical Resource: Empowering Investigators on NHGRI’s Cloud Infrastructure
• O61 – Improving Variant Classification for Genomic Medicine Through Evidence Calibration
• O38 – Patient-Centered, Multidisciplinary, Centralized, Longitudinal Clinical and Genomic Follow-Up: Development and Evaluation in the Undiagnosed Diseases Network (UDN)
• O40 – The E3 Genomics Pathways Program: Building a Sustainable Workforce in Medical Genetics and Genomics

Learning Objectives
At the conclusion of this session, participants should be able to:

• Utilize genomic analysis tools to support interpretation and clinical workflows
• Evaluate workforce and infrastructure models that support sustainable genomic practice
• Apply standardized frameworks to improve consistency and quality in genomic analysis

Presentations

• Rajarshi Ghosh, PhD, MS, FACMG
• Xinming Zhuo, PhD, FACMG
• STELLAR-AIM: State-of-the-Art Genetic Differential Diagnosis by AI Using Knowledge Extraction From Literature and Metabolomic, Genomic, and Phenotypic Data
  Christopher Yates
• A Semi-Quantitative Framework Curating Mechanism of Pathogenicity in Monogenic Conditions: A Consensus Effort of the Gene Curation Coalition
  Marina T. DiStefano, PhD, FACMG
• The AnVIL Clinical Resource: Empowering Investigators on NHGRI’s Cloud Infrastructure
  Matthew S. Lebo, PhD, FACMG
• Improving Variant Classification for Genomic Medicine Through Evidence Calibration
  Anne O'Donnell-Luria, MD, PhD, FACMG
• Patient-Centered, Multidisciplinary, Centralized, Longitudinal Clinical and Genomic Follow-Up: Development and Evaluation in the Undiagnosed Diseases Network (UDN)
  Emily Glanton, MS
• The E3 Genomics Pathways Program: Building a Sustainable Workforce in Medical Genetics and Genomics
  Yekaterina Unnikumaran, MS, MEd, ACMG

Polygenic Scores and Embryo Screening: Navigating the Clinical and Ethical Applications

Description
This session will explore the clinical utility and ethical considerations of polygenic scores, with a focus on polygenic embryo screening (PES). Presentations will cover the scientific foundations of polygenic scores, including data from large-scale research programs involving children and adults, as well as the statistical properties underlying PES—highlighting both its potential and its limitations.

The session will also examine the ethical and social implications of PES, including perspectives from patients and reproductive specialists, and will address the evolving commercial landscape. The discussion will provide a balanced view of the opportunities and challenges associated with this emerging area of genomic medicine.

ACMG-Designated Ethics Credit

Learning Objectives
At the conclusion of this session, participants should be able to:

• Examine the science behind polygenic scores for common diseases and traits
• Identify key points of tension and evolving perspectives regarding clinician and patient attitudes toward PES
• Evaluate claims about the accuracy, efficacy, and appropriate use of polygenic embryo screening

Presentations

• Welcome and Overview
  Huda B. Al-Kouatly, MD, FACMG
  Thomas Jefferson University
• The Science Behind Polygenic Scores
  Casey J. Brewer, PhD, FACMG
• Polygenic Embryo Screening: Statistical Properties
  Todd Lencz, PhD
• Ethical and Social Implications of Polygenic Embryo Screening
  Gabriel Lazaro-Munoz, PhD, JD
• Evolving Landscape of Polygenic Embryo Screening
  Laura Hercher, MA, MS, CGC
• Audience Questions, Comments, and Debate
  Panel Discussion and Q&A

Education and Research Strategies

Demystifying Neurology in Genetic Diagnosis: A Practical Approach for Geneticists

Description
As the role of genetics in neurological disease expands, so does the need for geneticists to evaluate neurological signs and symptoms. Features such as hypotonia, seizures, movement abnormalities, and developmental regression are often early indicators of an underlying genetic disorder.

This session demystifies neurology through a case-based approach, demonstrating how to incorporate brain MRI, EEG, and key elements of the neurological exam into diagnostic reasoning. Understanding whether hypotonia is central or peripheral, identifying characteristic EEG signatures, and recognizing MRI patterns such as leukodystrophies can enhance gene prioritization, variant interpretation, and diagnostic confidence.

Precise phenotyping is essential for selecting appropriate testing strategies, annotating variants in context, and applying frameworks such as ACMG/AMP guidelines—particularly in rare or complex cases where subtle neurological findings may be critical to diagnosis.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Apply components of the neurological exam to refine phenotyping in patients with suspected genetic disorders
• Identify the significance of MRI patterns in genetic diagnosis
• Incorporate EEG findings effectively into the diagnostic process

Presentations

• Welcome and Overview
  Maya Chopra, MD
• MRI in Genetic Diagnosis: Recognizing Patterns
  Andrea L. Gropman, MD, FACMG
• The Role of EEG in Genetic Diagnosis
  Wei-Liang Chen, MD, FACMG
  University of Washington
• Interactive Case-Based Discussion: Applying Neurology in Genetic Diagnosis
  Lisa Emrick, MD, FACMG
• Mastering the Neurological Exam: Central vs. Peripheral Hypotonia, Spasticity, and Movement Disorders
  Bharatendu Chandra, MBBS, FACMG
• Panel Discussion and Q&A

Leading the Field, Coming Out in Front

Description
This session will feature insights from leaders in medical genetics—including clinicians, a laboratory scientist, and a genetic counselor—who will share the skills and strategies that have shaped their careers.

The session will highlight key leadership topics such as problem solving, negotiation, prioritization, motivation, and building collaborative relationships. It will also explore the evolving roles of genetic professionals, particularly in the context of genetic testing performed by other specialties. Attendees will gain practical perspectives to support their day-to-day work and professional development.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Describe strategies to build and maintain high-performing teams
• Analyze different types of organizations and the relationship between leadership and organizational culture
• Explain key concepts for successful negotiation and problem-solving

Presentations

• Welcome and Overview
  Aya A. Abu-El-Haija, MD, MPH, FACMG
• The Differing View When Flying at Different Altitudes
  Wendy K. Chung, MD, PhD, FACMG
• Tick Talk Win: Time and Negotiation Power
  Aya A. Abu-El-Haija, MD, MPH, FACMG
• Following Your North Star: The Importance of Vision and Focus in Medical Genetics Leadership
  Bruce R. Korf, MD, PhD, FACMG
• Genomic Medicine Implementation in Health Systems: Leadership Opportunities for Genetic Professionals
  David H. Ledbetter, PhD, FACMG
  Florida State University
• Small Choices and Big Impact: Evolution of a Genetic Counselor Leader
  Sara Pirzadeh-Miller, MGC
• Panel Discussion and Q&A

Uniting Science, Standards, and Policy: Collaborative Approaches for Accelerating Pharmacogenomics Adoption

Description
Adverse drug events, including adverse drug reactions (ADRs), are the third leading cause of death in the United States. Genetic variation influences responses to many commonly prescribed medications, and pharmacogenomic (PGx) testing has been shown to reduce ADRs and improve treatment efficacy. Despite this, adoption remains limited and access varies widely.

Barriers include lack of training across medical specialties, heterogeneity in PGx testing, limited representation in clinical guidelines, inconsistent payer coverage, and low patient awareness. Improving adoption requires coordinated, collaborative efforts to address these challenges and strengthen policies that support broader access.

This session will introduce ClinPGx initiatives, including the Clinical Pharmacogenetics Implementation Consortium (CPIC) gene–drug guidelines, and highlight collaborative efforts to improve evidence evaluation, standardize testing, and expand access, coverage, and public awareness. Attendees will also learn how genetics professionals can engage in and contribute to these efforts.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Describe how ClinPGx resources, including CPIC guidelines, have advanced pharmacogenomics implementation worldwide, and identify strategies to address heterogeneity in PGx testing through standardization and stakeholder alignment
• List key considerations for implementing a clinical pharmacogenetics program within an electronic health record (EHR)
• Recognize opportunities to engage in federal and state advocacy to promote broader adoption of pharmacogenomic testing

Presentations

• Welcome and Overview
  Peter J. Hulick, MD, FACMG
• Advancing Pharmacogenomics Worldwide Through the Clinical Pharmacogenetics Implementation Consortium
  Roseann S. Donnelly, PharmD
• Standardizing Pharmacogenomics: A Multistakeholder Approach to Implementation and Access
  Sara Rogers, PharmD
• Electronic Health Record Considerations for Clinical Pharmacogenomics
  Peter J. Hulick, MD, FACMG
• Engaging in Federal and State Advocacy to Improve Adoption of Pharmacogenomic Testing
  Michelle L. McClure, PhD
• Panel Discussion and Q&A

Ethical, Legal, Social Issues (ELSI), Public Health and Policy

Hot Topics in Washington, DC and Impacts to Medical Genetics

Description
Throughout the first year of the current Administration, significant policy changes have impacted genetic science and medicine, with additional changes anticipated. This session will examine the most current and pressing policy developments affecting medical genetics and genomics, along with ACMG’s actions over the past year to address these challenges in alignment with its strategic priorities.

Topics will include federal legislation, agency rulemaking, regulatory oversight, and health equity considerations. Speakers will provide insight into how genetics professionals are navigating this rapidly evolving policy landscape, highlight anticipated future developments, and discuss ways institutions and individuals can engage to educate policymakers, discourage harmful policies, and advocate for positive change.

ACMG-Designated Ethics Credit

Learning Objectives
At the conclusion of this session, participants should be able to:

• Describe current federal legislative and regulatory initiatives impacting genetic services
• Examine the implications of recent federal actions affecting clinical and laboratory genetics
• Evaluate advocacy strategies that professionals can use to influence genetics-related policy
• Summarize actions taken by ACMG to support the field of medical genetics and advocate for its members

Presentations

• Welcome and Overview
  Michelle L. McClure, PhD
• A Year in Review: Significant Government Actions That Impacted the Field of Medical Genetics
  Marco L. Leung, PhD, FACMG
• The Current Policy Landscape: Where Do We Go From Here and What’s on the Horizon
  Michelle L. McClure, PhD
• ACMG in Action: Aligning Achievements With Strategic Priorities
  Mira Irons, MD, FACMG
• Why Advocacy Matters and How Individuals Can Help
  Susan D. Klugman, MD, FACMG
• Panel Discussion and Q&A

Health Services and Implementation

2026 ACMG Presidential Plenary Session- The Future of Expanded Newborn Genomic Screening: Promise and Practice

Description
Newborn screening remains one of the most successful public health initiatives. As genomic technologies advance and genetically informed therapies continue to emerge, new opportunities are arising to expand the scope and impact of newborn screening.

This Presidential Plenary, led by ACMG President Dr. Mira Irons, will highlight clinical advances, ethical considerations, and federal perspectives on the future of expanded newborn genomic screening.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Describe the scientific and clinical advances enabling expanded newborn genomic screening
• Evaluate the ethical, legal, and societal issues associated with genomic screening in newborns
• Discuss current implementation challenges and opportunities, including national initiatives
• Identify strategies for integrating genomic screening into clinical and public health practice

Presentations

• Welcome and Introduction
  Mira Irons, MD, FACMG
• ACMG Foundation Awards Presentations
  Nancy J. Mendelsohn, MD, FACMG
• Facing a New and Changing World: Stronger Together
  Mira Irons, MD, FACMG
• Clinical Implementation of Expanded Newborn Genomic Screening in the NHS
  David Bick, MD, FACMG
• From Promise to Practice: Genomic Sequencing in Newborn Screening – The BEACONS Study
  Ingrid A. Holm, MD, MPH, FACMG
• Ethical and Societal Considerations in Newborn Genomic Screening
  Aaron Goldenberg, PhD, MA, MPH
• Audience Questions and Discussion
  Panel Discussion and Q&A
• Closing Remarks
  Mira Irons, MD, FACMG

Late Breaking Open Forum: Expanded Newborn Genomic Screening—What’s Next?

Description
Continue the conversation from the Presidential Plenary in this attendee-driven, late-breaking session focused on the future of expanded newborn genomic screening. This interactive forum will provide time for audience questions, dialogue, and shared perspectives on clinical promise, ethical considerations, and real-world implementation challenges.

Join colleagues and leaders for an open exchange focused on what comes next—and how the genetics community can prepare for the evolving landscape of newborn genomic screening.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Describe emerging scientific and clinical developments shaping expanded newborn genomic screening
• Evaluate ethical, legal, and societal considerations associated with newborn genomic screening, including consent, equity, and follow-up responsibilities
• Discuss implementation barriers and practical strategies to support responsible integration of newborn genomic screening into clinical and public health practice

Presentations

• Discussion Session
  Mira Irons, MD, FACMG

Beyond the Genetics Clinic: Frontline Perspectives on Integrating Genomics in Specialty Care

Description
The limited growth and capacity of the medical genetics workforce, combined with increasing demand for genetic testing and follow-up care, has created a significant gap in access to genetic services. This gap underscores the need for alternative care models that expand access and integrate genetics into broader clinical practice.

This session will explore the role of non-genetics specialty providers in delivering point-of-care genetics within their clinical settings, highlighting both benefits and challenges from frontline perspectives. Through discussion with clinicians actively incorporating genetics into their practice, the session aims to identify opportunities to support sustainable care models, develop innovative strategies, and inform future training approaches and resources.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Compare implementation strategies across specialty clinics integrating genetic services into practice
• Identify advantages of integrating genetic services into specialty care settings
• Compare career paths of specialty care providers offering point-of-care genetics

Presentations

• Welcome and Overview
  Nathaniel Robin, MD, FACMG
• Cardiovascular Panelist
  Pankaj Arora
• Immunology/Rheumatology Panelist
  James Verbsky
• Ophthalmology Panelist
  Natario Couser, MD, FACMG
• Genomic Medicine in Kidney Care
  Natalie Vena
• Panel Discussion and Q&A

R. Rodney Howell Symposium - Delivering Pharmacogenomics at Scale: Implementation Strategies That Work

Description
Pharmacogenomics (PGx) promises improved medication outcomes through genetic testing and optimized prescribing. Robust evidence, consensus guidelines, and successful institutional implementations demonstrate its clinical value. However, significant barriers remain in scaling these successes for broad, system-wide adoption.

This session will highlight solutions from leaders in the field who have successfully addressed these challenges. Topics will include multidisciplinary care models, scalable education programs, electronic health record (EHR) and informatics design, and clinical decision support strategies to support widespread implementation of pharmacogenomics.

ACMG-Designated Ethics Credit

Learning Objectives
At the conclusion of this session, participants should be able to:

• Identify barriers that commonly impede large-scale genomic medicine initiatives
• Describe needs and challenges associated with pharmacogenomic laboratory test development and updates
• Describe innovative education strategies to improve healthcare practitioner competency in genomics
• Design effective clinical decision support and EHR-based approaches to increase adherence to practice guidelines
• Compare clinical care models that can scale pharmacogenomics across health systems

Presentations

• Welcome and Overview
  Philip E. Empey, PharmD, PhD
• Measuring What Matters: Defining and Tracking Success in Pharmacogenomics Programs
  Deepak Voora
• Developing and Updating Clinical Pharmacogenomics Tests: Challenges and Opportunities
  Sherin Shaaban, MD, PhD, FACMG
• Building the Foundation: Scalable Education Strategies for Pharmacogenomics Integration
  Philip E. Empey, PharmD, PhD
• Making Pharmacogenomics Actionable: From Guidelines to Clinical Decision Support
  Cyrine Haidar, PharmD
• Keeping Up With the Science: Managing Change in Pharmacogenomics Practice
  Henry M. Dunnenberger
• Panel Discussion and Q&A

TED-Style Talks: Advancing Genomics Engagement

Description
This session brings together three perspectives on expanding engagement in genomics. Dr. Shoumita Dasgupta will discuss mentorship in genomic education, emphasizing the importance of engaging learners holistically and authentically to broaden participation and support a future in genomic medicine that serves all patients.

Dr. Rebecca Ahrens-Nicklas will share her experience implementing personalized gene-editing therapies, highlighting the multidisciplinary collaboration required to advance complex genomic treatments. Sharon Terry will conclude by sharing her personal journey into genomics and emphasizing the power of collaboration in advancing the field and shaping the future of genomic medicine.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Identify methods to promote and sustain interest in genomics through effective mentorship
• Summarize the complexities involved in delivering personalized genomic therapies and strategies to address these challenges
• Illustrate the impact of collaboration in advancing genomic research and clinical care

Presentations

• Welcome and Introduction
  Ross A. Rowsey, PhD, FACMG
• Mentorship Matters: Harnessing Authentic Connection to Cultivate Tomorrow’s Leaders in Genomic Medicine
  Shoumita Dasgupta, PhD
• It Takes a Village to Advance Genomic Therapies
  Rebecca C. Ahrens-Nicklas, MD, PhD, FACMG
• Beyond Borders and Bias: Genomics for Health in the Hands of Those Who Need It
  Sharon F. Terry, MA

Laboratory Genetics and Genomics

Advances in Genomics with AI: From Patient Selection to Variant Analysis and Beyond

Description
Artificial intelligence (AI) has significantly advanced genomics, with applications such as facial analysis for genetic disorders, patient selection using electronic health records, and variant prioritization. These approaches streamline genomic analysis and support more efficient clinical workflows.

AI and large language models (LLMs) in natural language processing can annotate genetic variants by integrating phenotypic data and gene–disease relationships, enabling more precise and personalized care. These tools also support deep phenotyping, improving patient selection and genome interpretation. For example, recent work has demonstrated rapid genome analysis with turnaround times as short as 13.5 hours using automated systems.

Despite these advances, validation of AI tools remains complex, with limited guidance on best practices. This session will explore AI applications across the genomic workflow—from patient selection to variant analysis and reporting—while addressing validation strategies and considerations for equitable access. Panelists will discuss current capabilities and future directions of AI in precision medicine.

ACMG-Designated Ethics Credit

Learning Objectives
At the conclusion of this session, participants should be able to:

• Discuss the technical aspects, limitations, and future directions of AI methods in identifying patients for genomic testing and prioritizing clinically relevant variants
• Explore the application of AI tools in clinical practice across inpatient and outpatient settings, including best practices for validation, benchmarking, and implementation
• Recognize and evaluate the potential impact of AI on promoting equitable access to genomic medicine

Presentations

• Welcome and Overview
  Katarzyna A. Ellsworth, PhD, FACMG
• Harnessing AI for Early Identification of Rare Genetic Diseases
  Kym M. Boycott, MD, PhD, FRCPC, FCCMG
  University of Ottawa, Canada
• Leveraging AI Tools in Genomics to Improve Equitable Access to Care
  Ian M. Campbell, MD, PhD, FACMG
• AI-Driven Approaches to Variant Prioritization and Analysis
  Vaidehi Jobanputra, PhD, FACMG
• Best Practices in the Development and Validation of AI Tools in Genomics
  Kyle Farh
• Panel Discussion and Q&A

Beyond Uncertainty: Using Functional Assays for Clinical Variant Classification

Description
Reclassifying variants of uncertain significance (VUS) remains a major challenge in clinical genetics. Multiplexed Assays of Variant Effect (MAVEs) are emerging technologies that can assess the function of thousands of genetic variants simultaneously, providing powerful data to support variant interpretation.

This interactive session will introduce participants to functional data generated by MAVEs, demonstrate how to locate and evaluate clinical resources containing these data, and provide guidance on applying them within the ACMG/AMP variant classification framework. Through hands-on case examples, attendees will gain practical experience integrating functional evidence into real-world variant interpretation.

This session is designed for clinicians and laboratory professionals seeking practical tools and resources to incorporate emerging functional data into clinical practice.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Examine different classes of MAVEs implemented in clinical practice
• Identify clinical resources containing structured MAVE data for use in clinical settings
• Evaluate emerging guidance on translating functional data into evidence within the ACMG/AMP variant classification framework
• Apply MAVE-derived functional data to real-world cases to support variant reclassification decisions
• Assess limitations and potential pitfalls of using MAVE data to ensure accurate and responsible interpretation

Presentations

• Welcome and Overview
  Andrew B. Stergachis, MD, PhD, FACMG
• Panelist: Hands-On Case Examples
  Pankhuri Gupta, MGC
• Examine Different Classes of MAVEs That Have Been Implemented Into Clinical Practice
  Abbye E. McEwen, MD, PhD, MS
• Identify Emerging Clinical Resources of Structured MAVE Data That Can Be Used in Clinical Practice
  Melissa J. Landrum, PhD
• Examine Emerging ClinGen Guidance on Translating Functional Data Into Functional Evidence Within the ACMG/AMP Variant Classification Framework
  Lea M. Starita, PhD
• Hands-On Workshop: Applying Functional Data in a Real-World Variant Interpretation Scenario
  Rehan M. Villani
• Panel Discussion and Q&A

Dilemmas of Omic Technologies for Molecular Diagnosis of Rare Disease
Description
Omic technologies beyond short-read genomes—including long-read sequencing, transcriptomics, epigenomics, and metabolomics—are increasingly used to diagnose rare genetic conditions when standard testing is inconclusive. As these technologies transition from research to clinical settings, they introduce unique technical, clinical, ethical, and logistical challenges.

This interactive session will feature expert speakers presenting case-based debates on implementation dilemmas. Topics will include ethical considerations in returning results and managing incidental findings; technical challenges in pipeline analysis and defining disease thresholds; clinical reporting frameworks and result validation; and logistical barriers in results disclosure.

Each speaker will provide background context followed by pro/con perspectives on complex issues related to novel omic technologies. The session will begin with a technology overview and conclude with a panel discussion, offering practical insights for laboratories, clinical geneticists, and genetic counselors.

ACMG-Designated Ethics Credit

Learning Objectives
At the conclusion of this session, participants should be able to:

• Identify factors influencing the return of multi-omics results to rare disease research participants and strategies to enhance clinical translation
• Describe the translational process and implementation considerations for RNA sequencing as a CAP/CLIA-certified clinical diagnostic assay, including logistical challenges of long-read genomic and epigenomic testing
• Compare and evaluate ethical principles and challenges related to returning omics results to research participants

Presentations

• Introduction and Background
  Chloe Reuter, MS
• Beyond Short Reads: Practical Challenges in Implementing Long-Read Genomic and Epigenomic Testing
  Emily G. Farrow, PhD, MGC, FACMG
• Implementing Transcriptome RNA Sequencing in Rare Disease Diagnosis Within CAP/CLIA Standards
  Pengfei Liu, PhD, FACMG
• Practical and Ethical Considerations for Return of Multi-Omics Research Results to Rare Disease Patients
  Rachel Ungar, PhD
• Drawing the Line: Ethical Boundaries in Omic Result Disclosure
  Ellen F. Macnamara, MMSc
• Panel Discussion, Audience Q&A, and Closing Remarks
  Panel Discussion and Q&A

Genetic Counselor Forum - Consanguinity: Counseling, Laboratory and Ethical Considerations in the Genomic Era

Description
Genetic testing and counseling for individuals with consanguineous backgrounds require careful cultural and analytical sensitivity. The expansion of exome sequencing (ES) and genome sequencing (GS) has introduced new challenges in laboratory reporting within this context. In 2022, the ACMG Laboratory Quality Assurance Committee revised guidance on the interpretation and reporting of large regions of homozygosity (ROH) and suspected consanguinity or uniparental disomy. While ROHs have been widely discussed in the context of SNP array technology, their application to ES and GS remains less clearly defined, and laboratory practices continue to vary.

ROHs can support diagnosis by identifying candidate recessive disorders consistent with a patient’s phenotype, yet their utility in ES/GS is still evolving. Clinicians also face challenges in genetic counseling, particularly when consanguinity is undisclosed or involves complex social circumstances, such as minor parents or family planning decisions.

This session will address laboratory, clinical, ethical, and cultural considerations related to consanguinity, including case-based examples that highlight counseling and reporting dilemmas. Strategies for culturally sensitive communication and equitable access to genetic services will also be discussed.

ACMG-Designated Ethics Credit

Learning Objectives
At the conclusion of this session, participants should be able to:

• Review consanguinity and its relevance in genetics practice, including risk evaluation and testing options for consanguineous couples
• Apply ACMG technical standards for interpreting and reporting large regions of homozygosity and suspected consanguinity or uniparental disomy in genomic testing
• Examine challenges related to informed consent, privacy, and potential stigmatization, and apply culturally sensitive counseling strategies to support equitable access to genetic services

Presentations

• Welcome and Overview
  Klaas J. Wierenga, MD, MS, FACMG
• Introduction to Consanguinity
  Klaas J. Wierenga, MD, MS, FACMG
• Genetic Counseling in the Setting of Consanguinity
  Aaliya Ahmad, MS
• Laboratory Considerations for the Reporting of Consanguinity
  Catherine W. Rehder, PhD, FACMG
• Ethical and Social Implications of Consanguinity
  Aaron Goldenberg, PhD, MA, MPH
• Future Directions and Evolving Topics in the Setting of Consanguinity
  Madison Lake
• Panel Discussion and Q&A

Laboratory Diagnostic Challenges: Constitutional and Neoplastic Cases in Molecular, Cytogenomic, and Biochemical Genetics Specialties

Description
This session provides attendees with the opportunity to present cases with challenging diagnostic results or innovative approaches to fellow clinical laboratorians, fostering knowledge sharing and best practices. Cases from multiple diagnostic specialties—including molecular genetics, cytogenomics, and biochemical genetics—are welcome, spanning both constitutional and somatic contexts.

Each case presentation will be 10–15 minutes in length and limited to up to 10 slides. Presentations should include key phenotypic and laboratory findings in a narrative format, allowing for audience engagement in diagnostic reasoning and problem solving.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Apply structured approaches to interpret rare results across multiple clinical laboratory specialties
• Analyze case presentations from phenotype through test result interpretation, including differential diagnosis discussions
• Recognize and explain the clinical significance of testing results in rare and complex cases

Presentations

• Session Leads
  Devin Oglesbee, PhD, FACMG
  Yassmine Akkari, PhD, FACMG
• Case 1
  Maryam Abedi, PhD, MS
  Columbia University
• Case 2
  Fen Guo, PhD, FACMG
• Case 3
  John Murdoch, PhD
• Case 4
  Christina G. Tise, MD, PhD, FACMG
• Case 5
  Swetha Ramadesikan, PhD
• Case 6
  Mickey Kuo, MD, FACMG

Platform 5 - New Laboratory Techniches (Long read, OGM, RNA, PRS)

Description
Platform presentations represent the highest-ranking abstract submissions, selected by the Abstract Review Committee for oral presentation. Each platform presentation consists of a 13-minute presentation followed by a 2-minute question-and-answer period.

• O49 – WAFL: A Comprehensive, Multi-Omic Computational Workflow for Rare Disease Diagnostics Using Long-Read Sequencing
• O53 – Two Years of Clinical Long-Read Sequencing: Yes We Can Phase That—and Yes, It Is Reimbursable
• O55 – High-Throughput Functional Characterization of Splicing Variants in Inherited Retinal Degenerations Using a Multiplexed Assay Platform
• O35 – Challenges of RNA Sequencing Data Interpretation for the Reclassification of Genomic Variants of Uncertain Significance
• O58 – Increased Diagnostic Yield With Optical Genome Mapping in Pediatric Rare Disease Setting: 1-Year Clinical Experience at the Greenwood Genetic Center
• O33 – An LDL-C Polygenic Risk Score Enables Early Identification of Individuals at High Risk for Hypercholesterolemia Who May Otherwise Be Missed

Learning Objectives
At the conclusion of this session, participants should be able to:

• Evaluate novel laboratory technologies for diagnostic and clinical utility
• Interpret complex genomic findings generated by advanced sequencing methods
• Apply new techniques to enhance diagnostic yield and variant resolution

Presentations

• Alaa Koleilat, PhD, MS, FACMG
• Adelaide Fierti, MS
• WAFL: A Comprehensive, Multi-Omic Computational Workflow for Rare Disease Diagnostics Using Long-Read Sequencing
  Tanaya Jadhav
• Two Years of Clinical Long-Read Sequencing: Yes We Can Phase That—and Yes, It Is Reimbursable
  Emily G. Farrow, PhD, MGC, FACMG
• High-Throughput Functional Characterization of Splicing Variants in Inherited Retinal Degenerations Using a Multiplexed Assay Platform
  Kinga M. Bujakowska
• Challenges of RNA Sequencing Data Interpretation for the Reclassification of Genomic Variants of Uncertain Significance
  Matheus Wilke, MD, PhD
• Increased Diagnostic Yield With Optical Genome Mapping in Pediatric Rare Disease Setting: 1-Year Clinical Experience at the Greenwood Genetic Center
  Nikhil S. Sahajpal, PhD
• An LDL-C Polygenic Risk Score Enables Early Identification of Individuals at High Risk for Hypercholesterolemia Who May Otherwise Be Missed
  Sarah Hanks

Platform 8 - Rapid WGS and Newborn Screening

Description
Platform presentations represent the highest-ranking abstract submissions, selected by the Abstract Review Committee for oral presentation. Each platform presentation consists of a 13-minute presentation followed by a 2-minute question-and-answer period.

• O46 – Diagnostic Yield of Rapid Genome Sequencing in Critically Ill Infants With Cardiac Indications
• O62 – Comprehensive Reanalysis Increases the Diagnostic Yield of Rapid Genome Sequencing in Infantile Epilepsy
• O27 – Diagnostic Yield and Clinical Utility of Rapid Genome Sequencing in an Unrestricted NICU Cohort
• O32 – BeginNGS: Updates on Advancing Newborn Screening by Genome Sequencing Trial With Federated Learning Models
• O41 – Genomic and Clinical Correlation of G6PD Deficiency Identified by the GUARDIAN Expanded Genomic Newborn Screening Study
• O42 – Challenging Paradigms to Advance Rare Disease Screening and Early Diagnosis: Development of a Targeted Metabolomics Panel to Expand Newborn Screening

Learning Objectives
At the conclusion of this session, participants should be able to:

• Implement rapid genomic sequencing in acute and newborn care settings
• Interpret rapid sequencing results to support timely clinical decisions
• Incorporate reanalysis and follow-up strategies to improve diagnostic outcomes

Presentations

• Kandamurugu R. Manickam, MD, MPH, FACMG
• Zachary A. Whitt, MD, FACMG
• Comprehensive Reanalysis Increases the Diagnostic Yield of Rapid Genome Sequencing in Infantile Epilepsy
  Jimmy NH. Nguyen
• Diagnostic Yield and Clinical Utility of Rapid Genome Sequencing in an Unrestricted NICU Cohort
  Emily Hrach, MGC
• BeginNGS: Updates on Advancing Newborn Screening by Genome Sequencing Trial With Federated Learning Models
  Rebecca M. Reimers, MD, MPH, FACMG
• Genomic and Clinical Correlation of G6PD Deficiency Identified by the GUARDIAN Expanded Genomic Newborn Screening Study
  Brenna M. Boyd, MGC, MA
• Challenging Paradigms to Advance Rare Disease Screening and Early Diagnosis: Development of a Targeted Metabolomics Panel to Expand Newborn Screening
  Sarah H. Elsea, PhD, FACMG
• Diagnostic Yield of Rapid Genome Sequencing in Critically Ill Infants With Cardiac Indications
  Lisa Mullen Salz, MS

Rewriting the Reference: Laboratory and Clinical Applications of the New Human Pangenome Reference

Description
The human pangenome represents a major advancement in genomic science, offering a more complete and inclusive reference built from hundreds of diverse genomes. Unlike the current reference genome, which lacks global genetic diversity, the pangenome enables more accurate variant interpretation and improved diagnostic outcomes—particularly for historically underrepresented populations.

Designed for both laboratory and clinical professionals, this session will provide an overview of the human pangenome, its clinical applications, and the ethical and practical considerations for implementation. Case examples will illustrate its diagnostic impact and role in advancing equity in genetic testing. The session will also review tools and resources developed by the Human Pangenome Reference Consortium and discuss integration into laboratory pipelines and clinical workflows.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Define the pangenome, explain how it overcomes limitations of the traditional reference genome, and assess its impact on variant interpretation and diagnostic accuracy across diverse populations
• Analyze ethical considerations and implications for genomic equity in the development and application of the pangenome
• Evaluate practical considerations for implementing the pangenome in laboratory pipelines and clinical workflows

Presentations

• Moderator
  Matthew S. Lebo, PhD, FACMG
• Panelist
  Katherine E. Bonini, MGC, MA
• Panelist
  Matthew Schultz, PhD
  Ambry Genetics
• Panelist
  Karen Miga, PhD
  University of California, Santa Cruz
• Panelist
  Eimear E. Kenny, PhD
• Panel Discussion and Q&A

The Laws of the Ring: Diagnostic Algorithm, Formation Mechanisms, and Clinical Consequences

Description
This session highlights recent advances in understanding and diagnosing ring chromosome disorders, a group of rare chromosomal abnormalities characterized by dynamic mosaicism and clinico-cytogenomic heterogeneity. Topics will include diagnostic yield from a multi-center U.S. study, insights from a newly developed online database, and genomic sequencing approaches to understanding ring structure and formation mechanisms.

The session will also address the clinical significance of acquired ring chromosomes in hematopoietic and solid tumors, and incorporate perspectives from patients and caregivers. Updates from ACMG, CCMG, and ICHRC “Points to Consider” for laboratory analysis and interpretation of constitutional ring chromosomes will be discussed. A panel discussion will provide an opportunity to exchange ideas and consider best practices for diagnosis, management, and collaborative research.

Jessica A. Cooley Coleman, PhD, MB(ASCP)CM, Laboratory Genetics and Genomics Fellow at Greenwood Genetic Center, will present on behalf of Barbara R. DuPont.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Analyze diagnostic challenges and clinical–cytogenomic correlations of constitutional ring chromosomes, including the use of long-read sequencing to detect breakpoints and understand ring formation
• Evaluate diagnostic and prognostic implications of acquired ring chromosomes in hematopoietic and solid tumors, incorporating perspectives from patients, caregivers, and advocacy groups
• Summarize updates from the ACMG working group regarding the “Points to Consider” document for human ring chromosomes

Presentations

• Welcome and Overview
  Peining Li, PhD, FACMG
• Constitutional Ring Chromosomes from a Multi-Center Study and a Newly Developed Online Database
  Barbara R. DuPont, PhD, FACMG
• Unraveling Ring Chromosome Complexity and Ring Formation Mechanisms Using Whole Genome Sequencing
  Mei Ling Chong, PhD
• Acquired Ring Chromosomes and Extrachromosomal DNA (ecDNA) in Hematopoietic and Solid Tumors
  Ying Zou, MD, PhD, FACMG
• Points to Consider in Laboratory Diagnosis/Interpretation and Clinical Management of Ring Chromosomes
  Elizabeth M. Spiteri, PhD, FACMG
• Panel Discussion and Q&A

Prenatal Genetics

Challenge the Experts - Pediatric and Prenatal Diagnostic Dilemmas (rare knowns and unknowns)

Description
This session features an interactive format in which attendees present cases to a panel of experts and an audience of geneticists for discussion of differential diagnosis, treatment, and counseling options. Three prenatal and three pediatric cases—ranging from rare known diagnoses to unknowns—will be selected for discussion.

Presenters will have the opportunity to “challenge the expert” with their cases. Prenatal cases may include rare known or suspected genetic syndromes identified through ultrasound findings, with discussion of management and, when available, postnatal outcomes. Pediatric cases may include rare known conditions or previously undiagnosed cases.

Each presentation will be limited to 10 minutes, followed by 5 minutes of audience and expert discussion. Presenters are encouraged to focus on key clinical details, including pertinent positive and negative findings and prior testing results.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Present and discuss clinical cases from chief complaint through diagnosis
• Develop and contribute to differential diagnoses, recognizing key features of both common and rare disorders
• Evaluate diagnostic workups in the context of expert recommendations

Presentations

• Session Leads
  Chad Haldeman-Englert, MD, FACMG
  Keith A. Eddleman, MD, FACMG
• Prenatal Case 1
  Helene Martinovic-Bouriel
• Pediatric Case 1
  Amanda Toledo Hernandez, MD
• Prenatal Case 2
  Ena Arora
• Pediatric Case 2
  Henry J. Mroczkowski, MD, PhD, FACMG
• Prenatal Case 3
  Joselle O'Brien, MD, MA
• Pediatric Case 3
  Hector Mendez, MD, MS
• Expert Panelists
  Kim M. Keppler-Noreuil, MD, FACMG
  Karin J. Blakemore, MD, FACMG

Non-invasive Fetal Sequencing (NIFS) is coming: Are you ready?

Description
There are more than 7,000 known monogenic conditions, affecting approximately 1 in 50 individuals, with about 1 in 21 classified as rare. While some conditions may be detected prenatally through ultrasound findings or reproductive carrier screening, most are not identified until after birth, leading to delays in diagnosis, prolonged diagnostic odysseys, and missed opportunities for timely counseling regarding recurrence risks.

The diagnostic yield of exome and genome sequencing following invasive prenatal testing is now well established for fetal anomalies and is being explored in low-risk pregnancies. Emerging studies demonstrate that non-invasive fetal sequencing (NIFS) is feasible. As NIFS advances toward clinical implementation, important questions regarding reporting practices, informed consent, and equitable access must be addressed.

Learning Objectives
At the conclusion of this session, participants should be able to:

• Summarize the history and evolution of cell-free fetal DNA screening
• Describe current non-invasive fetal sequencing (NIFS) methodologies, including challenges, opportunities, and risks and benefits in both high- and low-risk prenatal settings
• Analyze key ethical considerations in the clinical use of NIFS

Presentations

• Welcome and Overview
  Ronald J. Wapner, MD, FACMG
• Cell-Free DNA Overview and Future Directions
  Neeta L. Vora, MD, FACMG
• Current NIFS Methodologies: Challenges and Opportunities
  Michael E. Talkowski
• Clinical Implementation of NIFS: Consent, Reporting Guidelines, and Results Return
  Jessica L. Giordano, MS
• Ethical Considerations of NIFS in Clinical Practice
  Marsha Michie
• Panel Discussion and Q&A

Reproductive Carrier Screening: Is It Time for Whole Genome Testing?

Description
Reproductive carrier screening is offered during pregnancy or preconception to assess the risk of having a child affected by autosomal recessive and X-linked genetic conditions. Carrier screening has evolved from testing for individual conditions, such as hemoglobinopathies and Tay-Sachs disease, to expanded panels assessing carrier status across hundreds to more than 1,000 genes.

In 2021, ACMG introduced a tiered framework recommending screening for 113 genetic conditions for all individuals, regardless of ancestry, based on carrier frequency and disease severity. This session will explore challenges in gene selection as new global population genomic data emerge, as well as opportunities presented by advancing genetic technologies. Ethical and clinical considerations in counseling individuals and couples, along with alternative screening models and their public health implications, will also be discussed.

ACMG-Designated Ethics Credit

Learning Objectives
At the conclusion of this session, participants should be able to:

• Summarize the process of selecting genes for carrier screening and assess how emerging population genomic data inform panel design
• Compare current technologies and evaluate the diagnostic yield of expanded reproductive carrier screening panels
• Identify and analyze ethical and clinical considerations in counseling individuals and couples identified as carriers

Presentations

• Welcome and Overview
  Mahmoud Aarabi, MD, PhD, FACMG
• What Genes to Screen: The Evolving Role of Carrier Frequency and Disease Severity
  Mahmoud Aarabi, MD, PhD, FACMG
• Technologies for Carrier Screening: Current and Future Considerations
  Honey Reddi, PhD, FACMG
• Carrier Screening 2026 – Advances, Controversies, and Counseling Dilemmas
  Susan D. Klugman, MD, FACMG
• Reproductive Carrier Screening in Australia: Lessons Learned
  Martin Delatycki
• Panel Discussion and Q&A