Dermatological manifestations in Noonan syndrome: A prospective multicentric study of 129 mutation‐positive patients

Summary

Background

Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and based on little dermatological expertise.

Objectives

To describe the dermatological manifestations of NS, compare them with the literature findings, and test for dermatological phenotype‐genotype correlations with or without the presence of PTPN11 mutations.

Methods

We performed a large, 4‐year, prospective, multicentric, collaborative dermatological and genetic study.

Results

One hundred and twenty‐nine patients were enrolled, including 65 with PTPN11‐NS, 34 with PTPN11‐NS with multiple lentigines (NSML), and 30 without PTPN11‐NS. Easy bruising was the most frequent dermatological finding in PTPN11‐NS, present in 53.8%. Multiple lentigines and café‐au‐lait macules (≥3) were present in, respectively, 94% and 80% of NSML linked to specific mutations of PTPN11. Atypical forms of NSML could be associated with NS with RAF1 or NRAS mutations. In univariate analysis, patients without a PTPN11 mutation showed (i) a significantly higher frequency of keratinization disorders (P=0.001), including keratosis pilaris (P=0.005), ulerythema ophryogenes (P=0.0001) and palmar and/or plantar hyperkeratosis (P=0.06, trend association), and (ii) a significantly higher frequency of scarce scalp hair (P=0.035) and scarce or absent eyelashes (P=0.06, trend association) than those with PTPN11 mutations.

Conclusions

Cutaneous phenotype of NS with a PTPN11 mutation is generally mild and non‐specific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities.

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