Page 98 - Clinical variability in Noonan syndrome with emphasison ear and eye

CHAPTER 6
Despite the limited number of implanted patients described in this case series, it is the largest number of implanted patients with a mutation in PTPN11 described in the literature. In 2009, Scheiber et al. reported two patients with NS. They received their CI at the ages of 2 and 4 years. These patients had missense mutations c.922A>G and c. 853T>C, both in the PTPN11 gene. Both of the patients presented with an absent development of speech and language. After implantation, the two-year-old child had a PTA of 25 dB HL and the four year old child was at 43 dB HL. Speech recognition scores were not presented (21). The four NS patients presented in our case series show comparable or better sound-field thresholds with CI.
In 2013, Ho-Suk Chu et al. described a girl with NSML that was implanted at the age of 5. The patient had a mutation in PTPN11, which was a missense mutation c. 1381G>A. One year after implantation, the patient was able to respond to loud sounds. However, she was not able to deliver meaningful communication. This is in contrast with the results in the current study. However, the minimal benefit described by Ho-Suk Chu et al. in 2013 was possibly caused by concomitantly acquired cerebral palsy, which might have limited her ability to develop language (22).
NS and NSML are allelic disorders that are caused by a different heterozygous missense mutation in the same gene. Because of the underling RAS-MARK pathway dysregulation, NS and NSML have numerous overlapping phenotypical features. However, both syndromes are heterogeneous. All of the patients described until now with NS and NSML using a CI had a mutation in the PTPN11 gene. In addition, out of all of the patients diagnosed with NS and NSML in our clinic, only patients with a mutation in the PTPN11 gene had severe to profound hearing loss and thus received a CI (Table 1).
Clinical recommendations and future studies
Not much is known about the phenotype-genotype correlation of hearing impairment in NS and NSML patients. Studies that show the pattern of hearing impairment over time would be useful. All of the patients presented in this study had a congenital onset of hearing impairment. One of the patients with NS seemed to have had a progression of hearing impairment over time. However, frequent otitis media might have played a role. The patient with NSML showed a severe progression in the first year of her life. Sensorineural hearing impairment is a feature that appears frequently in patients with NS and NSML. Therefore, otological and audiological examinations should be performed regularly.
There are some important phenotypic features to take into account in the work-up to cochlear implantation, including temporal bone abnormalities, bleeding disorders, and
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