Join us for Part Three of our captivating webinar series: "Advancements in Genomic Medicine: Navigating Health and Equity." 

📅 September 12, 2024

⏰ 12 pm – 2:00 pm ET

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What's New in Neurotherapeutics? Review of Select Treatments Approved for Rare Neurological Disorders

September 12, 2024 | 12:00 – 1:00 pm ET

Description:

An array of novel genetic therapies for monogenic neurological disorders have been recently approved by the Food and Drug Association (FDA) and European Union (EU) including anti-sense oligonucleotides, gene replacement and small molecules; in addition to several therapies that are currently in trial. This has led to changing natural histories and hope for patients living with these conditions, which were previously considered to be degenerative and life-limiting. Clinical trials and drug approvals for neurogenetic conditions have several unique caveats including novel biomarkers and endpoints such as specific motor and neurodevelopmental exam scales, seizure burden, neuroimaging, and electroencephalogram characteristics. An expert panel of neurogeneticists, neurologists and medical geneticists will discuss select therapies which were recently approved by the FDA and EU. This discussion will be covered under 4 presentations each focusing on a different neurological phenotype. The disorders and therapies were selected to provide a broad overview of the diversity of neurotherapeutics, and this discussion will help the audience to appreciate the pre-clinical and clinical research that led to the emergence of new treatments. The speaker will describe presenting clinical symptoms and diagnosis of these conditions through case presentation before discussing the mechanism of action, indications, and safety profile of the therapies.

• What’s New in Therapeutics of Genetic Epilepsies – This presentation will focus on new therapies approved for monogenic epilepsies. Dr. Kuntal Sen will review cyclic PMP infusion as the first treatment for Molybdenum Cofactor Deficiency type A, Daybue (trofinetide) for Rett syndrome and intraventricular enzyme replacement therapy for Batten disease/neuronal ceroid lipofuscinosis.

• What’s New in Therapeutics of Neuromuscular Disorders – This presentation will focus on new therapies approved for spinal muscular atrophy (SMA) and other monogenic neuromuscular disorders. Dr. Wendy Chung will review the three different therapies for SMA - Evrysdi (risdiplam), Spinraza (Nusinersen) and Zolgensma (onasemnogene abeparvovec-xioi). 

• What’s New in Therapeutics of Leukodystrophies – This presentation will focus on new therapies approved for monogenic white matter diseases. Dr. Adeline Vanderver will review SKYSONA/ elivaldogene autotemcel in treatment of X-linked Adrenoleukodystrophy (X-ALD), stem cell/ CD34+ cells (Libmeldy) therapy for metachromatic leukodystrophy (MLD) and repurposing strategies of janus kinase inhibitors in Aicardi Goutieres Syndrome (AGS). 

• What’s New in Therapeutics of Genetic Movement Disorders – This presentation will focus on new therapies approved for monogenic movement disorders. Dr. Sho Yano will review SKYCLARYS (omaveloxolone) in the treatment of Friedreich’s ataxia and Upstaza (eladocagene exuparvovec) for aromatic L-amino acid decarboxylase (AADC) deficiency. 

Target Audience

All healthcare professionals interested in the diagnosis, management, treatment, and prevention of genetic conditions and increasing their understanding of the genetic basis of common, chronic health problems affecting both children and adults will find the programming applicable to their practice. The ACMG Annual Meeting is targeted for the following professionals:

• Medical and clinical geneticists; genetic counselors; pediatric, obstetric, and maternal-fetal specialists; and all medical practitioners who are providing comprehensive diagnostic, management, and counseling services for patients with, or at risk for, genetically influenced health problems.
• Laboratory directors and technicians who conduct genetic testing.
• Researchers involved in the discovery of genetic disorders and treatments.
• Clinical, laboratory and research trainees of genetics and all biomedical sciences.
• Any healthcare and public health professionals who have an interest in medical and clinical genetics and genomics.
• Advocates for patients with genetic conditions and their families.

Agenda

Presentation followed by live Q&A. 

Learning Objectives

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

• Recognize presentations, diagnosis and indications for treatment in Rett syndrome, Batten disease and MoCD deficiency.
• Analyze the risks and benefits of treatment options and which treatment is most appropriate for SMA type 1, 2, and 3
• Recognize common clinical presentations, diagnostic tools and indications for treatment in ALD, MLD and AGS
• Discuss how therapies target the molecular pathways involved in Friedreich ataxia and AADC
• Review the endpoints in trials for neurogenetic disorders (motor and neurodevelopmental scales, seizure, EEG and MRI)

Adeline Vanderver, MD, Leukodystrophy Center 

Andrea Gropman, MD, FAAP, FACMG, FANA, Children's National Hospital

Kuntal Sen, MD, FACMG, Children's National Hospital

Loren Pena, MD, PhD, FACMG, University of Cincinnati

Sho Yano, MD, PhD, FACMG, National Institutes of Health

Wendy Chung, MD PhD, FACMG, Boston Children's Hospital

Dissecting Lateralized Overgrowth – Clinical and Molecular Diagnosis and Tumor Risk

September 12, 2024 | 1:00 – 2:00 pm ET

Description:

Lateralized overgrowth (LO) is characterized by asymmetric, increased growth or size of any part of the body and can be observed in defined overgrowth syndromes but can also occur as isolated lateralized overgrowth (ILO). For some of the well-described overgrowth syndromes including CDKN1C-related Beckwith-Wiedemann syndrome (BWS), PIK3CA-related overgrowth spectrum (PROS), AKT1-related Proteus syndrome (PS), and PTEN related hamartoma tumor syndrome (PHTS), an increased but heterogeneous tumor risk is known and, in some cases, periodic screening for neoplasms is recommended.

Historically, in children with ILO, there is a malignancy risk of approximately 5% for Wilms tumor and hepatoblastoma, however these cohorts did not molecularly distinguish mosaic syndromic cases from isolated cases.

Knowledge of underlying molecular causes of the various overgrowth syndromes has improved and genomic testing has become more readily available. Mosaicism and somatic variants play a significant role in the pathogenesis of certain overgrowth syndromes. Examples include mosaicism causing BWS and somatic variants or mosaicism in the genes of the PI3K/PTEN/AKT/TSC/mTORC1 signaling pathway, which can lead to distinct overgrowth conditions and may only be detected by deep sequencing of affected tissue. Recognizing individuals with specific overgrowth conditions caused by mosaicism can be challenging since the phenotypes can be more variable and significantly milder when compared to the classic forms of the disorders. We provide a clear approach for the evaluation of mosaicism or somatic variants in affected tissue in lateralized overgrowth with the goal to increase diagnostic accuracy. This in turn will improve the ability to develop more tailored tumor surveillance and help prevent unnecessary cancer screening, which can have adverse ramifications for the patients and their families.

Target Audience

All healthcare professionals interested in the diagnosis, management, treatment, and prevention of genetic conditions and increasing their understanding of the genetic basis of common, chronic health problems affecting both children and adults will find the programming applicable to their practice. The ACMG Annual Meeting is targeted for the following professionals:

• Medical and clinical geneticists; genetic counselors; pediatric, obstetric, and maternal-fetal specialists; and all medical practitioners who are providing comprehensive diagnostic, management, and counseling services for patients with, or at risk for, genetically influenced health problems.
• Laboratory directors and technicians who conduct genetic testing.
• Researchers involved in the discovery of genetic disorders and treatments.
• Clinical, laboratory and research trainees of genetics and all biomedical sciences.
• Any healthcare and public health professionals who have an interest in medical and clinical genetics and genomics.
• Advocates for patients with genetic conditions and their families.

Agenda

Presentation followed by live Q&A. 

Learning Objectives

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

1. Define diagnostic criteria of isolated lateralized overgrowth and distinguish from other overgrowth conditions.
2. Apply appropriate genetic testing strategy in patients with lateralized overgrowth.
3. Recognize phenotypic variability of lateralized overgrowth and integrate into the testing strategy.
4. Differentiate Proteus syndrome from other overgrowth syndromes.
5. Apply appropriate tumor risk and screening recommendations to individual patients with overgrowth conditions.

Angelika Erwin, MD, PhD, FACMG, Cleveland Clinic Cleveland

James Bennett, MD, PhD, FACMG, University of Washington

Jennifer Kalish, MD, PhD, FACMG, The Children's Hospital of Philadelphia

Julian Martinez-Agosto, MD, PhD, FACMG, University of California, Los Angeles
Matthew A. Deardorff, MD, PhD, FACMG, University of Southern California, Los Angeles