Page 107 - Clinical variability in Noonan syndrome with emphasison ear and eye

one patient with a BRAF mutation and this patient showed the lowest visual acuity with optic nerve hypoplasia. Furthermore we found high prevalence of ptosis, including a marked asymmetry between the right and the left eye. In conclusion, we found an extensive variety of congenital ocular abnormalities in Noonan syndrome patients characterized by developmental anomalies of the eyelids and associated with other ocular abnormalities in childhood.
In Chapter 4 we collected data in a large Noonan syndrome cohort and included ophthalmologic and genetic data of 105 patients. Besides the incidence of ocular manifestations in a retrospective and large cohort, we were also interested if the international Noonan syndrome guidelines have been followed (16). We hypothesized to confirm the ocular findings from our prospective cohort. We found reduced vision in seven patients, five of them had a mutation in RAF1, SHOC2, or KRAS gene. We also found high percentages of external ocular manifestations, refractive errors (myopia, hyperopia, and astigmatism), amblyopia and strabismus. Less frequent ophthalmic manifestations were nystagmus, keratoconus and optic disk excavation. It was remarkable to see that, although it is strongly recommended to do a comprehensive ocular examination as soon as the patient is diagnosed with Noonan syndrome, nine patients never visited an ophthalmologist and in three other patients there was a delay of many years before they had their first ocular examination. In the guidelines, referral for an ophthalmology assessment is recommended at the point of diagnosis. Further management and follow-up should be as deemed appropriate by the ophthalmologist (16).
Hearing and ear manifestations
Hearing impairment was linked to Noonan syndrome for the first time in 1976 (17) and is described in several Noonan syndrome studies (18,19). External ear anomalies are described in Noonan syndrome, mostly as part of facial dysmorphism. In Chapter 5 we presented data on hearing impairment, external ear anomalies and genetic findings in 97 patients. The hearing impairment was divided into four categories: sensorineural hearing impairment, mixed hearing impairment, permanent conductive hearing impairment, and temporary hearing impairment. Nine patients had sensorineural hearing impairment, and four of them had severe congenital hearing impairment. In all four patients with severe congenital hearing impairment, a PTPN11 mutation was found. They all received cochlear implants with good results. Interestingly, the two Noonan syndrome patients previously mentioned in literature who received cochlear implants, were both diagnosed with a mutation in the PTPN11 gene (20). Permanent conductive hearing impairment and mixed hearing impairment were found in 2
DISCUSSION AND SUMMARY
105
7