This marks our second full year as a nonprofit organization, and our third year for funding purposes.  I am changing the format of the newsletter this year to see if I can make it more email and webpage friendly.  If you are reading this, thank you for being a friend and/or active supporter of our organization.

Highlights for 2025

We published a meta-analysis of mosaic Ring 20 syndrome and the abstract for this paper will be attached to this newsletter.  (The full article is available by using the link provided).  We joined the Rare Epilepsy Network (REN) and Dr. James was selected to be on the Epilepsy Leadership Council of the American Epilepsy Society (AES).  We will be attending the AES annual meeting in December and manning a booth there (as well as helping with the REN table).  We have been helping with recruitment of some basic science investigations into Ring 20 and looking for ways to invest our time and your contributions. We have enhanced the website (ring20usa.com) and added Becca’s Ring 20 Basics. She wrote them so others would be able to give a few bullets if they were asked about what ring 20 is.

We continue to be closely aligned and collaborating with ring 20 UK and their group. We will collaborate on a paper designed to develop recommendations on the care of ring 20 patients with their board of scientific advisors (and hopefully it will be in the newsletter next year).

We are working to disseminate information on Ring 20, advocate in national organizations and the government for its recognition, research funding, and help families with affected family members.

Mosaic Ring 20 Syndrome A Meta-Analysis

Sarah Woodson, William D. James, Rudolf Roth, John S. Barbieri, Sherry Ershadi, Debby Cheng, and Mark P. Fitzgerald Neurol Genet 2025 (August issue)  https://doi.org/10.1212/NXG.0000000000200282  Abstract Background and Objectives  Ring 20 syndrome is a rare childhood-onset neurodevelopmental disorder caused by a postzygotic event leading to a structural change in the 20th chromosome. Next-generation sequencing (NGS) does not identify an abnormality in the most common mosaic form. Through a systematic review of the literature, we sought to identify clinically distinct characteristics that would trigger an order for a karyotype, which is the only definitive diagnostic test for this
condition.

Methods

A systematic literature review was performed reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. PubMed and Web of Science were searched from inception through January 8, 2025. Included studies reported on mosaic ring 20 syndrome. Two independent reviewers screened studies based on predefined criteria and extracted data from each study, which were quantitatively combined.

Results

A total of 70 publications reporting on 148 patients were included. Our review clearly reveals a distinct set of signs that should alert the informed neurologist to order a karyotype analysis at the first evaluation because it is currently the only method to properly diagnose this condition. Over 90% of cases which mention the seizure type describe multiply recurrent non convulsive status epilepticus. Patients generally do not have dysmorphia and are developing normally over the average of 7 years before seizure onset. The diagnosis of mosaic ring 20 syndrome should be considered in the setting of childhood-onset treatment-resistant epilepsy, particularly in the absence of focal abnormalities on brain MRI abnormalities, distinctive EEG findings, and pathogenic variants on short-read NGS.

Discussion

The diagnosis of mosaic ring 20 syndrome is via karyotype analysis. The current lag time from seizure onset to definitive diagnosis is 7.7 years. More widespread recognition of the distinctive clinical features of mosaic ring 20 syndrome should help shorten the diagnostic delay for affected individuals.

Becca’s Ring 20 Basics |A Patient’s Perspective

1. Rare type of seizure disorder
2. Cannot be cured by medicine
3. Does not cause me to convulse but may cause this in others
4. Causes staring
5. Problems thinking and responding
6. Sometimes talking and walking is difficult
7. Causes fatigue and depression
8. Causes short term memory loss
9. May cause social, learning and behavioral problems
Written by Becca James (this represents one patient’s perspective)

Conclusions of other papers of Significance this year

Long-term seizure and psychosocial outcomes of patients with ring chromosome 20 syndrome: A cohort study of 47 cases; Epilepsia; Volume66, Issue7, July 2025, p2444-53  Kentaro Tokumoto, Takuji Nishida, Hitoshi Ikeda, Hiroko Ikeda, Norihiko Kawaguchi, Satoshi Mizutani, Tokito Yamaguchi, Hideyuki Ohtani, Etsuko Yamazaki, Naotaka Usui, Katsumi Imai, Yushi Inoue

Key points

  • This retrospective cohort study of 47 patients investigated the outcomes ofseizure, cognitive function, comorbidities, and social living of patients with ring chromosome 20 syndrome.
  • In 30% of patients, seizures improved to a condition not or minimally disruptive to daily living.
    Favorable seizure outcome was significantly associated with lower mosaicism and higher lamotrigine use.
  • Fifty-seven percent of patients had intellectual disability, 17% had autism spectrum disorder, and 21% had psychiatric symptoms.
  • Social constraints in employment, independent living, driving, and marriage were common.

Response to vagus nerve stimulation in people with ring chromosome 20; Seizure: European Journal of Epilepsy; Volume 132, November 2025, Pages 13-19  Ariane Lajoie, David Dufresne, Chantelle Hrazdil, Émilie Riou, Kenneth A. Myers

Conclusion: While fewer than half of RC20 patients in this study reported a clear reduction in seizure frequency following VNS implantation, most reported benefits in other domains, including seizure severity, perceived cognitive function, behavior, and post-ictal recovery. Among those who did report seizure frequency reduction, the degree of improvement was highly variable. Some individuals achieved remarkable outcomes, including near-complete seizure control, while others experienced more modest yet still meaningful reductions.

Treasurer’s Report

In 2024, we received over $45,000 in donations – all of which will be applied to clinical or basic science research for Ring 20.  This was made possible by a few donors matching other donations. We also were awarded the Guidestar Bronze Seal of Transparency – demonstrating
our disclosure of information to prospective donors. In 2025, we have a team of donors that have agreed to double match donations – so every $1 in
donation should result in $3 going to research (up to $17,000 in funds will be double matched).

Looking to 2026

We hope to have a better network of families in North America that are tied into our organization. If you love to interact through social media and would like to use those skills to help Ring 20 USA, please let us know. Contact information is on the website.  We have several clinical and basic science projects that we are evaluating to see if we should help fund them – and hopefully get us closer to a cure.

Disclaimer

100% of the funds that are collected will go to clinical or basic science research – all administrative and meeting costs are covered by the leadership team.

Ring 20 USA, inc.
1530 Oconee Springs Blvd.
Statham, GA 30666