Largely preserved vestibular function despite severe-to-profound hearing loss in Noonan syndrome spectrum disorders.

PURPOSE: Noonan syndrome spectrum disorders (NSSDs) are RASopathies in which hearing impairment is common, whereas vestibular function has rarely been investigated systematically. This study aimed to evaluate auditory and vestibular function in patients with NSSDs and severe-to-profound hearing loss undergoing preoperative assessment for cochlear implantation. METHODS: Three patients who were clinically diagnosed with Noonan syndrome and later genetically classified within the NSSDs framework underwent comprehensive auditory and vestibular evaluations, including auditory brainstem responses, behavioral audiometry, caloric testing, and cervical/ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs), when feasible for age and cooperation. Genetic testing identified pathogenic PTPN11 variants. RESULTS: All three patients had severe-to-profound hearing loss. Pathogenic PTPN11 variants were detected—p.Glu139Asp in two patients and p.Tyr279Cys in one, the latter typically associated with Noonan syndrome with multiple lentigines (NSML), although lentigines were absent due to young age. Vestibular function was largely preserved in one patient and mildly impaired in two patients. oVEMP testing was successfully completed in only one case, whereas it could not be completed in the two infant cases because of limited cooperation. Imaging studies revealed no inner ear malformations or enlargement of the vestibular aqueducts. CONCLUSION: In this case series of pediatric patients with PTPN11-related NSSDs and severe-to-profound hearing loss, vestibular function was largely preserved or only partially impaired. These findings demonstrate a dissociation between auditory and vestibular function and suggest that differential vulnerability to molecular signaling abnormalities among sensory organs may be involved.