Analysis of Noonan syndrome cases detected in cohorts of patients with hearing loss

Noonan syndrome (NS) is a multisystem disease caused by pathogenic variants in genes involved in the RAS/MAPK signaling pathway, with pathogenic/likely pathogenic variants of the PTPN11 gene being the main causative variants in this syndrome. The clinical picture of NS includes a wide range of pathologies, including: facial dysmorphism, growth retardation, heart defects, pigmentation and intellectual development disorders, cryptorchidism, and hearing loss. The incidence of severe congenital sensorineural hearing loss and deafness in the samples of patients with NS varies from 8.7% to 19.1%. With the advent of high-throughput sequencing methods, mutations of the PTPN11 gene have increasingly become detected in non-target samples of patients with nonsyndromic hearing loss. This paper describes a case of previously undiagnosed Noonan syndrome with multiple lentiginious, identified by cascade testing, including WES analysis, in a sample of Buryat patients with congenital hearing disorders. The article discusses similar cases of identification of pathogenic variants in the PTPN11 gene identified in samples of patients with nonsyndromic hearing loss/deafness.

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