Title: Expanding Phenotypes of Female Heterozygotes in X-Linked Neurogenetic Conditions

Tuesday, October 21 | 2:00pm-3:00pm ET

Historically categorized as either "X-linked recessive" or "X-linked dominant," X-linked neurogenetic conditions have long been considered male-predominant. However, emerging research and clinical evidence reveal that female heterozygotes—once thought to be largely unaffected—can experience significant symptoms due to variability in X-inactivation (lyonization). This paradigm shift is reshaping how these conditions are understood, diagnosed, and managed.

Join us for a one-hour webinar exploring the evolving clinical phenotypes of females with X-linked neurogenetic disorders. Through expert-led presentations featuring clinical cases, neuroimaging, genetic insights, and updated terminology, this session will provide valuable updates for clinicians, researchers, and genetic counselors.

Featured Presentations:

• Kuntal Sen, MD, FACMG: Foundations of X-linked inheritance, lyonization, and inclusive terminology in genetics
• Andrea Gropman, MD, FAAP, FACMG, FANA, FCNS: Neuroimaging and clinical spectrum of Ornithine Transcarbamylase (OTC) deficiency in females
• Stephen Chrzanowski MD, PhD: Duchenne Muscular Dystrophy in female carriers and lessons from newborn screening
• Nishitha Pillai, MD: Diagnosis and management of X-linked Adrenoleukodystrophy (X-ALD) in females
• Jirair Bedoyan, MD, PhD, FACMG: Phenotypic variability in PDHA1-related Pyruvate Dehydrogenase Complex deficiency

Learning Objectives

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

1. Discuss the mechanisms leading to variable penetrance and phenotype in heterozygotes with X-linked conditions.
2. Explain the different phenotypes and data from multi-modal imaging in OTC heterozygotes.
3. Summarize presentations in X-ALD females, pathophysiology, diagnostic/management strategies and emerging therapies.
4. List DMD diagnostic strategies, clinical manifestations and appropriate management in DMD heterozygote females.
5. Summarize presentations in PDHA1 females, pathophysiology, diagnostic/management strategies.

CME AMA PRA Category 1^TM, & CME Other

Accreditation

The American College of Medical Genetics and Genomics is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation
The American College of Medical Genetics and Genomics designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Claiming your Educational Credits

Complete the activity and carefully complete the evaluation form. The deadline to claim educational credits is within 30 days from the date of the activity. Educational credit requests after this date will not be accepted.

Learner Data Consent

ACMG Education reports learner data to respective agency boards and you will be asked for consent during the evaluation process. Your compliance with deadlines and completing evaluations are part of the process in meeting learner needs and ACMG’s education mission.