Neurodevelopmental Disorders and Rett Syndrome: An Update from the 2025 ANS Meeting

Neurodevelopmental disorders (NDDs) are a group of conditions with early onset that affect multiple domains of brain function, including cognition, motor abilities, behavior/communication, and seizure activity. Because patients may present with overlapping combinations of intellectual disability, motor impairment, autism spectrum features, and epilepsy, accurate recognition and coordinated management can be challenging.

This activity outlines the clinical framework used to evaluate NDDs, including the four core functional domains and common etiologies such as genetic, chromosomal, and acquired causes. It highlights developmental epileptic encephalopathies (DEEs) and their distinction from other epilepsy syndromes, emphasizing the relationship between seizures and broader developmental impairment. The activity also underscores the importance of carefully evaluating seizure-like events in patients with NDDs, as not all episodic behaviors represent epileptic seizures.

Rett syndrome is presented as a key example within the NDD spectrum. Core topics include its genetic basis involving MECP2 mutations, the typical age of onset, and the characteristic stages of the disorder, including early developmental slowing, regression, and later stabilization. Clinical features such as stereotyped hand movements, gait abnormalities, breathing irregularities, autonomic dysfunction, and seizure risk are highlighted, along with common diagnostic challenges and associated comorbidities.

The activity also addresses evolving therapeutic approaches, including the role of disease-specific treatment with trofinetide alongside symptomatic management and multidisciplinary care. Emphasis is placed on coordinated care involving neurology, primary care, rehabilitation specialists, and allied health professionals, as well as the importance of supporting patients with NDDs, including Rett syndrome, across the lifespan and during the transition from pediatric to adult care.

Learning Objectives:
Upon completion of this activity, participants should be able to:

• Recognize early clinical indicators across rare neurodevelopmental disorders to support timely referral and intervention
• Select and apply appropriate advanced diagnostic strategies to inform prognosis and guide patient management.
• Enhance confidence in therapeutic decision-making for patients with neurodevelopmental disorders.
• Incorporate multidisciplinary coordination into care planning to improve patient outcomes and quality of life.