A Novel Variant of ARID1B-Related CSS in a Rwandan patient: A Case Report

Abstract

INTRODUCTION: CSS (CSS) is a rare neurodevelopmental disorder characterized by developmental delay, intellectual disability, hypotonia, distinctive craniofacial dysmorphism, and hypoplasia or aplasia of the distal phalanges or nails, particularly of the fifth digits. Pathogenic variants involving genes encoding components of the Switch/Sucrose Non-Fermentable chromatin-remodeling complex especially ARID1B gene critical for embryonic development and gene regulation represent the most common molecular cause of the syndrome. Although advances in genomic technologies have improved recognition of CSS worldwide over the past 3 decades, reports from sub-Saharan Africa remain limited. CASE PRESENTATION: We report a male patient referred to Rwanda Military Teaching Hospital, Pediatric Department in Medical genetic unit for global developmental delay and feeding difficulties. Clinical examination revealed, hypotonia, developmental milestone delay, coarse facial appearance, sparse scalp hair, thick eyebrows, long eyelashes, broad nasal bridge, anteverted nostrils, low-set ears, micrognathia, and hypoplastic toenails. Results: Conventional cytogenetic analysis demonstrated a male karyotype (46, XY). Whole exome sequencing-based copy number variants analysis identified a 7.3 Mb interstitial deletion involving chromosome 6q25.3–q25.1 encompassing the ARID1B gene. The finding was confirmed by multiplex ligation-dependent probe amplification, establishing the diagnosis of CSS type 1. The patient was managed in multidisciplinary team approach including physiotherapy and speech therapy and he demonstrated clinical improvement. CONCLUSION: This report describes the first genetically confirmed case of CSS in Rwanda. It highlights the diagnostic utility of advanced molecular genetic testing in children with developmental delay and dysmorphic features and underscores the importance of expanding access to clinical genetic services in resource-limited settings to reduce diagnostic odyssey and timely patient management.