Highlights

Website activated!
In August, after a volunteer effort by Wynn Thomas, we were able to put ring20usa.com online. The website is able to receive donations (and we are already in the midst of our 2024 giving campaign)

Scientific Achievements
One paper was published this year, trying to bring to light the current difficulties with diagnosing this rare syndrome.


Inside This Issue
1  Continuing Articles across Pages
1  Instructions for Using this Template
4  Inserting and Editing Pictures

Welcome to our Newsletter

This is our first newsletter, and we hope to put one out at a minimum of once a year. Ring 20 USA, inc is a nonprofit that was created in December 2023. We actually had a successful season of giving last year, and have been receiving gifts this year as well.

Regarding giving, the officers of the nonprofit are committed to paying all administrative expenses themselves, so that 100% of giving will go to fund research and education of Ring 20 syndrome.

You are receiving this newsletter because you either gave in the past, or have a connection to Ring 20 syndrome.

Ring 20 Syndrome One Parent’s Perspective

The time spent with my daughter, who happens to have Ring 20, has covered a wide scope of emotions. We have experienced great joy as well as extreme sadness and every emotion in between those two as mother and daughter. For the first 71⁄2 years of her life, my daughter was strong, athletic, active and shy. Our family, my husband, son and daughter, had a social, busy lifesyle which included sports and school activities. Then things began to change in the spring of 1988 when we noticed our daughter “losing focus” on the soccer field and not responding to our requests. She was a fierce competitor in soccer and on the swim team, winning many awards for her athletic accomplishments. Once at swim practice she was zipping down the lane, turned and then returned in slow motion. In one soccer game she was on defense when she just stopped challenging any opponent. We called to have her come to the side with no success. These were some of the first signs of what we now know, decades later, is Ring 20 syndrome.

Between the spring of 1988 and the fall of 1989 doctors tested her for diabetes which was negative , prescribed inhalers for asthma which she used but didn’t result in positive results and had EEGs which were negative. We knew that physical activity brought on the syndrome. My husband was able to get a stationary bike into the EEG room. My daughter rode for less than 10 minutes and went into seizure. From that point on we knew her diagnosis was epilepsy. The official diagnosis was atypical partial complex seizures. I always said that “atypical” was the most important word in her diagnosis,

From that point on my daughter was prescribed every known epilepsy drug for her diagnosis. Some had no relief whatsoever. Others caused dizziness, double vision, hallucinations, nausea, mood swings, lack of or increased appetite,and/or a severe negative affect on her cognitive ability. Every time a new drug comes on the market, my daughter has opted to try it. The trials are wearing on the patient and the family. We attempt a trial when we can free our calendars as best we can. When my daughter was school age we waited for a summer or winter recess to start the trial. Life then revolves around administering doses of the new medicine, noting changes, if any, in symptoms. There’s often a need to devote extra attention to nurturing, nursing and bolstering my daughter’s self worth due to depression during these times. Throughout many trials, the best combination of epileptic medicine for my daughter has been Depakote and Trileptal.

We have spent many overnight stays in hospitals for EEG scans. We also had a stay in the hospital to start the Ketogenic Diet. This proved to be an unsuccessful treatment, as well. The diet was extremely difficult for my daughter to follow through the 3 month trial. She is strong and always perseveres through hard challenges. It also affected our family life dramatically. We needed to prepare minute portions of food in precise measurements that we didn’t eat. Who eats slabs of butter and cream with one bean?! The meals were strange. Then we ate without her so that she wouldn’t see us having a normal meal. This changed our family dynamics because we always have and still do eat together as a family.

once our daughter entered high school, friends began joining school teams, getting their driver’s licenses, dating and my daughter became isolated at home just when teenagers were spreading their wings. Who could she take her sadness and ire out on? Her family. Teen years through mid twenties were rough years emotionally for her and us. After graduation from high school, we eventually found a 2 year vocational school in PA for kids with disabilities. It was about 3 hours from our home. It was the first time my daughter opted to live on her own. It proved to be a growing experience for my daughter to live with peers having a wide variety of medical issues. After her time away from family, she chose to come home. Luckily, we have room for her and truly love having her with us. We know she is safe, taking her meds, traveling with us, getting to doctors regularly and socializing with our family and her friends who know and understand her diagnosis well. Those same people are a great support system for us. I know I can share anything with them. My husband is my best support and we have a strong love that has been a successful marriage for over 50 years. We are blessed.

Over time we have learned that having dogs in our home calms my daughter during seizures and any anxious periods. Their presence in her life is the best of all medicines. She also is able to have lessons at a therapeutic horse farm where she grooms and rides her favorite horse, Betty. This is an essential part of her well being.

I tell my friends and family that Becca has taught me more than anyone on Earth. She has ensured that I became a more patient individual. This not only helped Becca, but the students I teach as well as everyone in my family. Her fund of knowledge for nature and animals is limitless. She has opened my eyes to the wonder of nature that I didn’t stop to completely enjoy earlier. Our love for one another is strong and supportive. We are blessed to have her in our lives.

What do I hope for? Research studies that lead to a cure for Ring 20 so that my daughter and others living with Ring 20 can be rid of the daily seizures that hinder them from being all that I know they are capable of being. By Ann James

Ring 20 syndrome: A call to action

William D. James, Rudolf Roth, Mark Fitzgerald First published: 05 March 2024

https://doi.org/10.1111/epi.17941 (Epilepsia)

The Centers for Disease Control and Prevention (CDC) reports that 470 000 children have active epilepsy.1 Of those, at least 50% have a known or presumed genetic etiology.2 Given that the overall yield of whole exome sequencing is ~20% to 25%, even if all eligible patients were tested with next-generation sequencing (NGS) modalities, there would remain more than 175 000 children without a genetic diagnosis for their symptoms.

The National Society of Genetic Counselors recently developed a practice guideline that recommends genetic testing in all children and adults with unexplained epilepsies to help improve the number of patients who achieve a diagnosis.4 These guidelines rely heavily on NGS tests for any patients who do not have a clinical phenotype that warrants targeted testing. This recommendation is expected to improve the rates of diagnosis for many; however, certain patients with a potentially recognizable phenotype may be missed by NGS methods if the clinician does not consider these disorders specifically. Notably, most patients with a diagnosis of ring 20 syndrome [r(20)] cannot be diagnosed by NGS methodologies and must receive a karyotype in order to render the diagnosis correctly.

Structural changes in chromosomes may lead to epilepsy. r(20) was first described in 1977. To date, only ~200 cases have been reported.5 As opposed to other ring syndromes, two-thirds of patients with r(20) are of the mosaic type. The only method to diagnose these patients is via karyotype analysis.

The common presenting profile of a child with r(20) includes typical neurodevelopment until age 5 to 8 with no dysmorphia or birth injury and no family history of epilepsy, who begins to experience treatment-resistant seizures suddenly. Many have nonconvulsive status epilepticus, lasting minutes to hours. Nocturnal seizures, hallucinations, and seizures with impaired awareness are characteristic. Magnetic resonance imaging is normal. Electroencephalography findings include interictal mild slowing or bursts in the frontotemporal regions of sharply contoured theta activity, with a peak frequency of 5 Hz. Although this is the typical profile, variations in age at onset and neurodevelopment depend upon the degree of mosaicism.

The natural history and comorbidities of r(20) are not well described. There may be cognitive impairment, behavioral problems, and other dysfunctions that develop over time, either due to the disease itself or to seizure burden.

We suspect that the true incidence and prevalence of r(20) has yet to be determined given the underutilization of karyotype in current genetic testing paradigms. We recommend ordering karyotyping in a patient with intractable childhood-onset seizures for whom a genetic analysis with NGS methodologies has been unrevealing. This will close a practice gap using the current algorithm.

By remaining cognizant of r(20), clinicians can choose karyotype as the appropriate test in the proper clinical circumstance. In doing so, clinicians can ensure that children and families with r(20) can receive an accurate and timely diagnosis, preventing a protracted diagnostic odyssey for these patients.

REFERENCES

1. Zack MM, Kobau R. National and state estimates of the numbers of adults and children with active epilepsy — United States, 2015. MMWR Morb Mortal Wkly Rep. 2017; 66: 821– 825.

2. Thomas RH, Berkovic SF. The hidden genetics of epilepsy-a clinically important new paradigm. Nat Rev Neurol. 2014; 10(5): 283–292.

3. Sheidley BR, Malinowski J, Bergner AL, Bier L, Gloss DS, Mu W, et al. Genetic testing for the epilepsies: a systematic review. Epilepsia. 2022; 63: 375–387.

4. Smith L, Malinowski J, Ceulemans S, Peck K, Walton N, Sheidley BR, et al. Genetic testing and counseling for the unexplained epilepsies. J Genet Couns. 2023; 32: 266–280.

5. Peron A, Catusi I, Recalcati MP, Clazari L, Laizza L, Vignoli A, et al. Ring chromosome 20 syndrome: genetics, clinical characteristics, and overlapping phenotypes. Front Neurol. 2020; 11: 1–15.

2023 REVIEW

BECAME NONPROFIT

We applied for (and were accepted) for nonprofit status with the IRS

GIVING REPORT

Gifts in 2023 totaled $2160 and helped us get off to a great start. These gifts were given by 44 separate donors.

COLLABORATION MADE

Partnered with Ring20UK to form a collaborative team to get closer to a cure for Ring 20.

ONE CONFERENCE ATTENDED

Dr. James attended a conference on Rare Diseases sponsored by Ultragenyx. At this conference he developed relationships that helped in the formation of our nonprofit.

2024 HIGHLIGHTS

WEBSITE DEVELOPED

Our website went live in August and began receiving donations in September

GIVING REPORT

Gifts in 2024 have already exceeded 2023 and we are entering a matching giving campaign (gifts up to a total of $10,000 will be matched by a donor.

ONE CONFERENCE ATTENDED

Dr. Roth attended a Rare Drug Development Symposium sponsored by Global Genes and and Exchange Forum sponsored by Rare-X

RESEARCH REPORT

We are partnering with investigators on sampling blood of Ring 20 patients to look deeper at chromosomal abnormalities and analyzing data from GeneDx regarding long sequencing.

Additionally, we are working on writing papers about Ring 20 to increase knowledge of this rare disease in the literature.

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