Scott, Matt, Misko, Albert, Liu, Lyric Yang and Sverdlov, Alex (2025) Analysis of retrospective natural history data collected from patients with SYNGAP1-related disorders: a preliminary examination of the Ciitizen database. Orphanet journal of rare diseases : OJRD.

Abstract

Background: SYNGAP1-related disorder (SRD) is a rare neurodevelopmental disorder caused by genetic mutations and variants. One major challenge is the characterization of the SRD, which requires assessment of several outcomes. We considered natural history data from the Ciitizen database on 65 patients with SRD. Eight data domains have been explored: demographics, genetics, growth parameters, standardized clinical scales, developmental skills, neurological examinations, hospitalizations, and seizures. Exploratory analysis tools such as visualization, summary statistics, and non-parametric statistical modeling were utilized.

Results: Age at SRD diagnosis (median [IQR]=3 [2, 5] years; [min, max]=[1, 17] years) was similar by sex. No evidence of a high frequency allele in SYNGAP1 was found, indicating no dominant mutation in this patient population. Growth parameters of SRD children appeared normal across height, weight, and head circumference. Developmental data was indicative of delayed development and language reversion. Standardized assessment data were largely sparse. Neurological exam data demonstrated ataxia and muscle tone issues. Hospitalization data highlighted substantial healthcare burden, largely due to seizures. Absence, atonic, and myoclonic where the most common types of seizures.

Conclusion: Ciitizen data provides important insights into the natural course of SRD. This information can provide utility in clinical practice and inform the design of clinical trials in SRD. Limitations to our analysis include sparsity of standardized clinical scales data, crude statistical methodology, and bias induced by patients with older ages of diagnoses.

Item Type:	Article
Date Deposited:	07 Oct 2025 00:45
Last Modified:	07 Oct 2025 00:45
URI:	https://oak.novartis.com/id/eprint/53080