BACKGROUND: Olfactory dysfunction (OD) is an underrecognized feature of CHARGE syndrome (CS), often associated with CHD7 mutations and structural anomalies of the olfactory system. This systematic review examines the burden, assessment methods, and clinical correlates of OD in CS.
METHODOLOGY: A systematic review was conducted in accordance with PRISMA guidelines and registered with PROSPERO (CRD420251040500). A comprehensive search of six databases up to May 2025 was performed. Two independent reviewers screened, extracted data, and assessed study quality. A narrative synthesis was performed.
RESULTS: From 1,643 records, 16 studies met inclusion criteria. Most were retrospective cohort studies and employed clinical diagnostic criteria for CS, with a subset reporting CHD7 mutation data. OD was most frequently identified radiologically. Psychophysical testing and self/parent reports were less common. Neurodevelopmental delays, feeding/swallowing issues, and reduced quality of life were reported in association with OD, but causal relationships remain unclear.
CONCLUSIONS: OD is highly prevalent in CS, often exceeding 80%, yet remains underrecognized. Radiologic imaging and electrophysiological techniques may be alternatives when psychophysical testing is not feasible. Future research should focus on validating paediatric-specific and developmentally appropriate olfactory assessments and integrating olfaction into quality-of-life frameworks. OD should be considered for inclusion in revised CHARGE diagnostic criteria.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)