# Analysis of retrospective natural history data collected from patients with SYNGAP1-related disorders: a preliminary examination of the Citizen database

## TL;DR

This study analyzes data from 65 patients with SYNGAP1-related disorder to understand its natural history and clinical features.

## Contribution

The study provides preliminary insights into SRD using the Citizen database, highlighting developmental delays and seizure types.

## Key findings

- Growth parameters in SRD children were normal, but developmental delays and language reversion were observed.
- Seizures, particularly absence, atonic, and myoclonic types, were the main cause of hospitalizations.
- No dominant SYNGAP1 allele change was found, suggesting genetic heterogeneity in the patient population.

## Abstract

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

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 change in SYNGAP1 was found, indicating no dominant variant in this patient population. Growth parameters of SRD children appeared normal in terms of height, weight, and head circumference. Developmental data were 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 seizures were the most common types.

Citizen data provide important insights into the natural course of SRD. Our findings not only provide utility in clinical practice of SRD but also contribute valuable insights to guide the development of SRD clinical trials. Limitations to our analysis include sparsity of standardized clinical scales data, crude statistical methodology, and bias induced by patients with older ages of diagnoses.

The online version contains supplementary material available at 10.1186/s13023-025-03918-7.