Abstracts

Rationale: There is limited information currently in the literature regarding this ultra-rare form of epilepsy. This research aims to elicit possible connections between genetic mosaicism and phenotypic presentations, which could help inform clinical practice.


Methods: This study was conducted in association with Ring 20 Research and Support UK CIO, an international charity organisation supporting patients with r20 syndrome and their families. A patient-orientated survey was undertaken by each participant or their caregiver, exploring topics including demographics, diagnostic challenges, genetic basis, seizure types, associated symptoms, and treatments. This survey was completed with participants present via an online structured interview format.

The survey questions included closed-question multiple choices, open-ended free-text and Likert scales. Participants were recruited via advertisement via the Ring 20 Research and Support UK group. The interviews were conducted over a 4-month period (August – November 2023) with participants internationally.


Results: A total of 84 respondents undertook this survey across 19 countries. The demographics are illustrated in Table 1, with a skewed distribution.The average age of epilepsy onset in this cohort was 6.45 (SD = 3.82, 0 – 16, 95% CI: 0.84) which was normally distributed (Shapiro-Wilk W = 0.977, p > 0.05), with an age range of 0 to 16 years. 2 participants aged 0 years had in utero testing to confirm diagnosis. The average age of R20 syndrome diagnosis was 9.74 (SD = 6.89, 0 – 37, 95% CI: 1.50). On average, participants had a delay of 3.31 years in R20 syndrome diagnosis from seizure onset (p< 0.05, two-tailed paired T test).

This study demonstrated an average of 34.38% (SD = 22.9%, n = 62, 0 - 100%, 95% CI: 5.87) percentage of R20 mosaicism, which was not normally distributed (Shapiro-Wilk W = 0.95, p < 0.05). The percentage of mosaicism inversely correlates with the age of seizure onset (rs = -0.08, n = 62, p >0.05, Spearman’s correlation) and with the interval in years to R20 diagnosis (rs = -0.03, n = 62, p >0.05). However, these inverse relationships were not statistically significant.

On average, participants are currently on 2 (SD = 1.2, 0 – 5, 95% CI: 0.31) antiepileptic drugs (AEDs) and previously tried 5 (SD = 4.2, 0 – 18, 95% CI: 0.91) number of AEDs. There was a statistically significant positive correlation in the percentage of mosaicism and number of AEDs required (H = 52.40, n = 62, 0 – 5, p< 0.05, Kruskal-Wallis test).


Conclusions: To our knowledge, this is the largest study using a survey collecting demographic and clinical data pertaining to patients with Ring 20 syndrome. An inverse correlation between percentage of r20 mosaicism and age of seizure onset and length of r20 diagnosis from seizure onset is seen, but further studies are required to illustrate statistical significance. Interestingly, a statistically significant positive relationship between degree of mosaicism and number of AEDs could help drive clinical practice of initiating patients with higher percentages of r20 mosaic lineages on an increased number of AEDs from baseline rather than a slow up-titration for improved seizure control.


Funding: N/A