Page 108 - Clinical variability in Noonan syndrome with emphasison ear and eye

CHAPTER 7
patients. Temporary hearing impairment was seen in 20 patients, due to otitis media with effusion. Possible underlying anomalies causing hearing impairment in Noonan syndrome described in literature are inner ear anomalies, including reduced numbers of spiral ganglion cells, dislocated endolymphatic sacs and vestibular aqueducts, and enlarged lateral semicircular canals. The combination of inner ear anomalies and conductive hearing impairment due to otitis media, may lead to mixed hearing impairment. Also chronic and multiple otitis media infections may lead to sensorineural hearing impairment. Congenital hearing impairment is a problem in Noonan syndrome, but hearing impairment may also show progression during life.
Sensorineural hearing impairment is found in Noonan syndrome and other RASopathies including Noonan syndrome with multiple lentigines. Counseling and special care make it possible for the majority of patients with a RASopathy and hearing impairment to function normally in adulthood. Cochlear implantations play an important role in patients with severe bilateral sensorineural hearing impairment. Therefore we have reported the outcome of five children with cochlear implants in Chapter 6. The case series describes four patients with Noonan syndrome and one with Noonan syndrome with multiple lentigines, all with a mutation in the PTPN11 gene. After cochlear implantation, the audiological results, including speech recognition, increased in all five patients. However in four of them it was not age appropriate due to severe hearing loss in the first years of life an intellectual disability. All the patients in our study, and the patients described in literature, are diagnosed with severe to profound hearing loss and with a mutation in the PTPN11 gene (21). Sensorineural hearing impairment is a feature that occurs on regular base in Noonan syndrome and other RASopathies including Noonan syndrome with multiple lentigines and therefore audiological and otological examinations should be performed in all patients.
Future prospects
Currently, we still use clinical features for the diagnosis of Noonan syndrome and other RASopathies and we support the clinical diagnosis with genetic testing and confirming germline mutations if available. Molecular testing of RASopathies is improving with next generation sequencing and new molecular studies are needed to discover more causative mutations in the nearby future.
Furthermore, research is necessary to better understand the RAS/MAPK pathway. By better understanding of the mechanisms that drive genotype to phenotype in the
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