Case Report: Chung-Jansen Syndrome Associated with a Novel PHIP Deletion and Lysosomal Storage–Like Features

Background: Chung–Jansen syndrome (CHUJANS, OMIM #617991) is a rare neurodevel-opmental disorder caused by heterozygous pathogenic variants in the PHIP gene. Core clinical features include developmental delay, intellectual disability, behavioral abnor-malities, childhood-onset overweight or obesity and dysmorphic features. Case presentation: We report a case of a girl diagnosed with CHUJANS, who presented with global developmental delay, hypotonia, minor facial anomalies, and early failure to thrive followed by childhood-onset obesity. Biochemical and radiological investigations revealed abnormalities suggestive of a lysosomal storage disorder (LSD), including per-sistent urinary glycosaminoglycan excretion, transiently decreased lysosomal enzyme activities, and dysostosis multiplex–like skeletal features. Comprehensive genetic testing excluded primary and secondary LSDs and identified a novel de novo heterozygous in-frame deletion in PHIP, classified as an ACMG class IV/V variant. Longitudinal follow-up demonstrated gradual developmental progress with emerging behavioral difficulties and progressive nephromegaly. Conclusion: This case report describes a novel de novo PHIP in-frame deletion associ-ated with a typical CHUJANS syndrome phenotype and additional LSD–like features not previously reported in this condition; whether these findings are secondary to PHIP dys-function or represent an independent process remains unclear and warrants further in-vestigation.