Page 53 - Clinical variability in Noonan syndrome with emphasison ear and eye

OCULAR MANIFESTATIONS OF NOONAN SYNDROME: A PROSPECTIVE STUDY OF 25 PATIENTS
Figure 2. Limited ocular motility of patient 19.
Abduction deficit ODS in (A) maximal gaze to the right, and (B) maximal gaze to the left.
Intraocular pressure
Intraocular pressure was measured and relatively low (< 10 mm Hg) intraocular pressure was found in five of 23 examined patients (22%). None of the patients were found to have ocular hypertension or glaucoma.
Genotype
Genetic analyses were performed in 23 patients. Mutations were found in 22 patients (Table 1): 19 patients had a PTPN11 mutation (76%). The three other patients revealed, respectively, a SOS1 mutation, a BRAF mutation and a KRAS mutation. Within the PTPN11 gene mutations, the c.922A>G was the most common mutation occurring in six patients. Patient numbers 4 and 5, and 12 and 13 were sister and brother pairs. The c.236A>G changes were found within these two families (Table 1).
Ocular phenotype-genotype correlation
In the three single mutations described in our cohort, respectively SOS1, BRAF and KRAS mutation, different ocular manifestations as compared to PTPN11 mutations were found. The patient with the BRAF mutation (Patient 19) had poor vision, infantile sensory nystagmus, strabismus and bilateral optic nerve hypoplasia. He was the only patient in our NS cohort who was severely visually impaired. The patient with the KRAS mutation (Patient 22) had the highest hypertelorism index (En-En/Zy-Zy), and the patient with the SOS1 mutation (Patient 14) showed the highest number of prominent corneal nerves and severe ptosis with a relatively good levator muscle function. In patients with PTPN11 mutations, a variety of all different ocular abnormalities was found (Table 1).
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