Clinical phenotypes and cochlear implant outcomes in patients with PTPN11-associated noonan spectrum disorders: Insights from a genetically screened cohort

OBJECTIVES: We characterized the clinical features of PTPN11-related deafness and evaluated the outcomes of cochlear implantation in affected patients. METHODS: Whole-exome sequencing and bioinformatic analyses were performed in a cohort of 467 individuals with congenital sensorineural hearing loss to identify potential genetic etiologies. Four patients harboring PTPN11 variants were reviewed for their clinical characteristics and post-implantation auditory rehabilitation outcomes. RESULTS: PTPN11 variants were identified in four patients (Cases 1-4). A missense variant c.1391G > C (p.Gly464Ala) in exon 12 was detected in Case 1 and the recurrent variant c.836A > G (p.Tyr279Cys) in exon 7 was identified in Case 2. Both patients were diagnosed with Noonan syndrome with multiple lentigines. Missense variants c.1510A > G (p.Met504Val) in exon 13 and c.923A > G (p.Asn308Ser) in exon 8 were found in Cases 3 and 4, respectively; both were diagnosed with Noonan syndrome. Cases 1, 2, and 4 underwent cochlear implantation and demonstrated favorable postoperative auditory and speech outcomes. CONCLUSION: Our study provides a comprehensive characterization of auditory, speech and systemic phenotypes in PTPN11-related Noonan spectrum disorders and demonstrates that cochlear implantation is highly effective for severe-to-profound hearing loss. These findings emphasize the value of early genetic diagnosis and emphasize the importance of coordinated, interdisciplinary management.