You are leaving Medscape Education
Cancel Continue
Log in to save activities Your saved activities will show here so that you can easily access them whenever you're ready. Log in here CME & Education Log in to keep track of your credits.



Exploring the Spectrum of Rett Syndrome: Diagnosis, Symptom Burden, and Care

  • Authors: Constance L. Smith-Hicks, MD, PhD; Alan K. Percy, MD; Jeffrey Neul, MD, PhD
  • CME / ABIM MOC Released: 3/7/2023
  • Valid for credit through: 3/7/2024
Start Activity

  • Credits Available

    Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 1.00 ABIM MOC points

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for neurologists, pediatricians, primary care physicians (PCPs), and other clinicians who treat patients with Rett syndrome.

The goal of this activity is for learners to be better able to assess for and diagnose Rett syndrome and to increase their knowledge of clinical data on therapies being studied for the management of Rett syndrome.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Presenting symptoms frequently associated with Rett syndrome
    • Diagnostic criteria for Rett syndrome
    • Clinical data on emerging treatments for the management of Rett syndrome
    • Current approaches to treating specific symptoms of Rett syndrome
  • Demonstrate greater confidence in their ability to
    • Assess and diagnose Rett syndrome


Medscape, LLC requires every individual in a position to control educational content to disclose all financial relationships with ineligible companies that have occurred within the past 24 months. Ineligible companies are organizations whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.

Disclosures for additional planners can be found here.


  • Constance L. Smith-Hicks, MD, PhD

    Associate Professor of Neurology
    Johns Hopkins University School of Medicine
    Kennedy Krieger Institute
    Baltimore, Maryland


    Participation by Dr. Constance L. Smith-Hicks does not constitute or imply endorsement by the Johns Hopkins University or the Johns Hopkins Hospital and Health System.

    Constance L. Smith-Hicks, MD, PhD, has no relevant financial relationships.

  • Alan K. Percy, MD

    Professor of Pediatrics, Neurology, Neurobiology, Genetics, and Psychology-Emeritus
    Sarah Katherine Bateh Endowed Professorship for Rett Syndrome-Emeritus
    University of Alabama at Birmingham
    Birmingham, Alabama


    Alan K. Percy, MD, has the following relevant financial relationships:
    Consultant or advisor for: ACADIA Pharmaceuticals Inc.; Neurogene
    Contracted researcher for: ACADIA Pharmaceuticals Inc.

  • Jeffrey Neul, MD, PhD

    Professor of Pediatrics
    Division of Neurology, Pharmacology, and Special Education
    Annette Schaffer Eskind Chair
    Vanderbilt Kennedy Center
    Vanderbilt University Medical Center
    Nashville, Tennessee


    Jeffrey Neul, MD, PhD, has no relevant financial relationships.


  • Pakinam Aboulsaoud, PharmD

    Senior Medical Education Director, Medscape, LLC


    Pakinam Aboulsaoud, PharmD, has no relevant financial relationships.

  • Megan Breuer, PhD

    Medical Writer, Medscape, LLC


    Megan Breuer, PhD, has the following relevant financial relationships:
    Consultant/advisor for: Paratek Pharmaceuticals, Inc. (former)
    Owns stock in (publicly traded): Bristol Myers Squibb Company; Johnson and Johnson; Paratek Pharmaceuticals, Inc.; Vertex Pharmaceuticals Incorporated

Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC


    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.

Accreditation Statements

In support of improving patient care, Medscape, LLC is jointly accredited with commendation by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

    For Physicians

  • Medscape, LLC designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Aggregate participant data will be shared with commercial supporters of this activity.

    Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page. To receive AMA PRA Category 1 Credit™, you must receive a minimum score of 70% on the post-test.

Follow these steps to earn CME/CE credit*:

  1. Read about the target audience, learning objectives, and author disclosures.
  2. Study the educational content online or print it out.
  3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. We encourage you to complete the Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate, but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period, you can print out the tally as well as the certificates from the CME/CE Tracker.

*The credit that you receive is based on your user profile.


Exploring the Spectrum of Rett Syndrome: Diagnosis, Symptom Burden, and Care

Authors: Constance L. Smith-Hicks, MD, PhD; Alan K. Percy, MD; Jeffrey Neul, MD, PhDFaculty and Disclosures

CME / ABIM MOC Released: 3/7/2023

Valid for credit through: 3/7/2024



  1. Fu C, et al. Consensus guidelines on managing Rett syndrome across the lifespan. BMJ Pediatr Open. 2020;4:e000717.
  2. Inuzuka LM, et al. MECP2-related conditions in males: a systematic literature review and 8 additional cases. Eur J Paediatr Neurol. 2021;34:7-13.
  3. The Human Protein Atlas: MECP2. Updated December 7, 2022. Accessed February 7, 2023.
  4. Collins BE, et al. Rett syndrome and MECP2 duplication syndrome: disorders of MeCP2 dosage. Neuropsychiatr Dis Treat. 2022;18:2813-2835.
  5. Banerjee A, et al. Towards a better diagnosis and treatment of Rett syndrome: a model synaptic disorder. Brain. 2019;142:239-248.
  6. Ip JPK, et al. Rett syndrome: insights into genetic, molecular and circuit mechanisms. Nat Rev Neurosci. 2018;19:368-382.
  7. Neul JL, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010;68:944-950.
  8. Kyle SM, et al. Rett syndrome: a neurological disorder with metabolic components. Open Biol. 2018;8:170216.
  9. Nielsen JB, et al. A 77-year-old woman and a preserved speech variant among the Danish Rett patients with mutations in MECP2. Brain Dev. 2001;23(suppl 1):S230-S232.
  10. Fu C, et al. Multisystem comorbidities in classic Rett syndrome: a scoping review. BMJ Pediatr Open. 2020;4:e000731.
  11. Percy AK. Progress in Rett syndrome: from discovery to clinical trials. Wien Med Wochenschr. 2016;166:325-332.
  12. Fonzo M, et al. Evidence-based physical therapy for individuals with Rett syndrome: a systematic review. Brain Sci. 2020;10:410.
  13. Killian JT, et al. Caretaker quality of life in Rett syndrome: disorder features and psychological predictors. Pediatr Neurol. 2016;58:67-74.
  14. Zoghbi HY. Rett syndrome: what do we know for sure? Nat Neurosci. 2009;12:239-240.
  15. Ivy AS, et al. Rett syndrome: a timely review from recognition to current clinical approaches and clinical study updates. Semin Pediatr Neurol. 2021;37:100881.
  16. Percy AK, et al. Rett syndrome diagnostic criteria: lessons from the natural history study. Ann Neurol. 2010;68:951-955.
  17. Gold WA, et al. Rett syndrome: a genetic update and clinical review focusing on comorbidities. ACS Chem Neurosci. 2018;9:167-176.
  18. Chahrour M, et al. The story of Rett syndrome: from clinic to neurobiology. Neuron. 2007;56:422-437.
  19. Cosentino L, et al. Rett syndrome before regression: a time window of overlooked opportunities for diagnosis and intervention. Neurosci Biobehav Rev. 2019;107:115-135.
  20. Patrizi A, et al. Chronic administration of the N-methyl-D-aspartate receptor antagonist ketamine improves Rett syndrome phenotype. Biol Psychiatry. 2016;79:755-764.
  21. Smith-Hicks CL, et al. Randomized open-label trial of dextromethorphan in Rett syndrome. Neurology. 2017;89:1684-1690.
  22. A study to evaluate ketamine for the treatment of Rett syndrome. Accessed February 12, 2023.
  23. Kaufmann WE, et al. ANAVEX2-73 (blarcamesine), a sigma-1 receptor agonist, ameliorates neurologic impairments in a mouse model of Rett syndrome. Pharmacol Biochem Behav. 2019;187:172796.
  24. Study of ANAVEX2-73 in patients with Rett syndrome. Accessed February 12, 2023.
  25. ANAVEX2-73 study in pediatric patients with Rett syndrome (EXCELLENCE). Accessed February 12, 2023.
  26. Glaze DG, et al. A double-blind, randomized, placebo-controlled clinical study of trofinetide in the treatment of Rett syndrome. Pediatr Neurol. 2017;76:37-46.
  27. Glaze DG, et al. Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome. Neurology. 2019;92:e1912-e1925.
  28. Neul JL, et al. Design and outcome measures of LAVENDER, a phase 3 study of trofinetide for Rett syndrome. Contemp Clin Trials. 2022;114:106704.
  29. Bassuk AG. Gene therapy for Rett syndrome. Genes Brain Behav. 2022;21:e12754.
  30. Safety and efficacy of TSHA-102 in adult females with Rett syndrome (REVEAL adult study). Accessed February 15, 2023.
« Return to: Exploring the Spectrum of Rett Syndrome: Diagnosis, Symptom Burden, and Care
  • Print