Page 78 - Clinical variability in Noonan syndrome with emphasison ear and eye

CHAPTER 5
Table 2. External anomalies in cohort of 97 patients
External ear anomalies
Low set ears Posteriorly rotated ears Thickened helices Protruding ears Dysplastic ears
Total external
ear anomalies
Number of PTPN11 patients (n=48)
69 (71%) 34 28 (28%) 11 18 (18%) 7 14 (14%) 8 4 (4%) 3 75 (77%) 39
SOS1 RAF1 (n=10) (n=5)
8 4 6 2 1 1 1 1 0 0 8 4
SHOC2 KRAS (n=5) (n=1)
4 0
3 0
3 0
0 0
0 0
4 0 80% 0%
MAP2K2 A2ML1 (n=1) (n=1)
1 0
0 0
0 0
0 0
0 0
1 0 100% 0%
External ear anomalies
81% 80% 80%
Information of the external ear anomalies was obtained from retrospective descriptions during visits to the clinical genetics, otorhinolaryngology and pediatric departments. External ear anomalies were described in 75 patients out of the total cohort of 97 patients (77%). These are summarized in Table 2. Low-set ears are the most frequent external anomaly, described in 69 patients (71%), followed by posteriorly rotated ears in 28 patients (29%), thickened helices in 18 patients (19%), protruding ears in 14 patients (14%) and dysplastic ears in 4 patients (4%). In 22 patients no external ear anomalies were described.
Hearing impairment
In total 44 patients had visited an otorhinolaryngology department (Table 3). SNHI was found in nine patients (20%, age 0-47 years). Four of the nine patients had severe congenital HI and in three patients progression of the HI was seen (Table 4). HI and mutation analysis of the patients with both SNHI and mixed HI (MHI) is shown in Table 4. Permanent conductive hearing impairment was measured in two patients with a PTPN11 mutation (age 11 and 17). They both had tympanic membrane perforation. It was noted that after tympanoplasty their conductive HI persisted. MHI was measured in two patients (age 17 and 25), one with a PTPN11 mutation and one without a known mutation. In this last patient without a mutation, DNA analysis for PTPN11, SOS1, RAF1, KRAS, BRAF and MAP2K2 was performed. Both of these patients had multiple OME infections in their medical history. The mutation analysis for 20 patients with temporary HI due to otitis media (resolved between age 2-47 years), are shown in Table 1. In total 33 patients with hearing impairment were found (34% of the total cohort). Four patients with severe congenital SNHI received cochlear implants (CI) with good results. The audiological results of the non-congenital SNHI are shown in Figure 1.
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