Page 76 - Clinical variability in Noonan syndrome with emphasison ear and eye

CHAPTER 5
Burgt (3,19). In most patients DNA analysis was available. Because most of the patients were seen by otorhinolaryngologists, speech and hearing centers and pediatricians elsewhere, data were collected on both external ear anomalies and hearing impairment after written informed consent. Clinical geneticists, pediatricians or otorhinolaryngologists described the external ear anomalies. Forty-four patients were seen by an otorhinolaryngologist and in 38 of them audiological tests were performed. The other six patients were seen by otorhinolaryngologists with complaints of otitis media and other otorhinolaryngological complaints. In this group no audiological tests were done because they had no complaints of hearing impairment. We included 97 patients for the analysis of external ear anomalies and the 44 patients seen by an otorhinolaryngologist for the analysis of HI. HI is defined as a high-frequency pure tone average (PTA) (average of 1, 2 and 4 kHz) of more than 20dB. In most patients with HI analysis, pure-tone audiometry and speech audiometry were performed. In children, depending on the age, pure-tone audiometry, visual reinforcement audiometry (VRA), Brainstem Evoked Response Audiometry (BERA), Auditory Steady State Responses (ASSR), and/or impedance audiometry were used for audiological evaluation. The results of the hearing tests were collected retrospectively and were performed in different medical centers. In the Netherlands audiological investigations are performed in Speech and Hearing Centers and in otorhinolaryngology departments and 44 patients went to these centers and departments. We assume that in the six patients without audiological examinations, there were no clinical signs of HI.
Results
Genotype
NS was clinically diagnosed and DNA analysis was performed in 80 patients. Mutations were found in 71 patients. In 48 patients a mutation was found in PTPN11, in 10 patients in SOS1, in five patients in RAF1 and in a further five patients in SHOC2. Unusually, we found KRAS in one patient, MAP2K2 in another patient and A2ML1 in a further patient. In 9 patients DNA analysis was performed and no mutation was found. All of them were screened for the PTPN11 gene and six of them were screened for other NS gene mutations. In our cohort of 97 patients, in 71 (73%) a mutation in one of the NS-genes confirmed the diagnosis of NS. The exact genotypes and the number of patients with HI are summarized in Table 1.
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