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Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation.
Br J Dermatol 2019; 180(6):1438-1448BJ

Abstract

BACKGROUND

Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and are based on limited 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

Overall, 129 patients with NS were enrolled, including 65 patients with PTPN11-NS, 34 patients with PTPN11-NS with multiple lentigines (NSML), and 30 patients with NS who had a mutation other than PTPN11. Easy bruising was the most frequent dermatological finding in PTPN11-NS, present in 53·8% of patients. Multiple lentigines and café-au-lait macules (n ≥ 3) were present in 94% and 80% of cases of NSML linked to specific mutations of PTPN11, respectively. 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

The cutaneous phenotype of NS with a PTPN11 mutation is generally mild and nonspecific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities.

Authors+Show Affiliations

Department of Dermatology, Saint-Eloi Hospital, Competence Centre for Rare Skin Diseases, Montpellier, France. University of Montpellier, Montpellier, France. INSERM U1058, Montpellier, France.Department of Paediatric Dermatology, Femme-Mère-Enfant Hospital, University of South Réunion, Saint-Pierre Réunion, France. Department of Dermatology, University of Rennes, Rennes, France.Department of Paediatric Dermatology, Robert-Debré Hospital, AP-HP, Paris, France.Department of Dermatology, L'Archet 2 Hospital, Nice, France. University of Nice, Nice, France.Department of Paediatric Dermatology, Pellegrin University Hospital of Bordeaux, Bordeaux, France.Department of Clinical Genetics, Sud Hospital, Rennes, France. University Hospital of Rennes, Rennes, France.University of Montpellier, Montpellier, France. Department of Medical Information, Epidemiological and Clinical Research Unit, La Colombière Hospital, Montpellier, France.Department of Clinical Genetics, Robert-Debré Hospital, AP-HP, Paris, France. University of Paris-Diderot, Paris, France.Department of Dermatology, Saint-Eloi Hospital, Competence Centre for Rare Skin Diseases, Montpellier, France. University of Montpellier, Montpellier, France.Department of Clinical Genetics, Arnaud de Villeneuve Hospital, Montpellier, France.Department of Dermatology, Brabois Hospital, Nancy, France. University of Nancy, Nancy, France.Department of Clinical Genetics, Robert-Debré Hospital, AP-HP, Paris, France. University of Paris-Diderot, Paris, France.Department of Clinical Genetics, Arnaud de Villeneuve Hospital, Montpellier, France.University of Nice, Nice, France. Department of Clinical Genetics, L'Archet 2 Hospital, Nice, France.University of Montpellier, Montpellier, France. Department of Paediatric Cardiology, Arnaud de Villeneuve Hospital, Montpellier, France.Department of Paediatric Dermatology, Reference Centre for Rare Skin Diseases, Necker-Enfants Malades Hospital, AP-HP, Paris, France.Department of Clinical Genetics, Femme-Mère-Enfant Hospital, University of South Réunion, Saint-Pierre Réunion, France.University of Montpellier, Montpellier, France. Department of Paediatric Endocrinology, Arnaud de Villeneuve Hospital, Montpellier, France.Department of Clinical Genetics, Pellegrin University Hospital of Bordeaux, AP-HP, Paris, France.Department of Dermatology, La Timone Hospital, AP-HM, Marseille, France. University of Marseille, Marseille, France.Department of Dermatology, Larrey Hospital, Reference Centre for Rare Skin Diseases, Toulouse, France. University of Toulouse, Toulouse, France.University of Montpellier, Montpellier, France. Department of Medical Information, Epidemiological and Clinical Research Unit, La Colombière Hospital, Montpellier, France.Department of Dermatology, CH, Perpignan, Perpignan, France.Department of Dermatology, Saint-Eloi Hospital, Competence Centre for Rare Skin Diseases, Montpellier, France.University of Marseille, Marseille, France. Department of Clinical Genetics, La Timone Hospital, AP-HM, Marseille, France.Department of Clinical Genetics, Arnaud de Villeneuve Hospital, Montpellier, France.Department of Clinical Genetics, Arnaud de Villeneuve Hospital, Montpellier, France.University of Marseille, Marseille, France. Department of Clinical Genetics, La Timone Hospital, AP-HM, Marseille, France.University of Paris-Diderot, Paris, France. Department of Genetic Biochemistry, Robert-Debré Hospital, AP-HP, Paris, France.Department of Clinical Genetics, Arnaud de Villeneuve Hospital, Montpellier, France.Department of Clinical Genetics, Arnaud de Villeneuve Hospital, Montpellier, France. INSERM U1183, Montpellier, France.Department of Clinical Genetics, Robert-Debré Hospital, AP-HP, Paris, France. University of Paris-Diderot, Paris, France.University of Paris-Diderot, Paris, France. Department of Genetic Biochemistry, Robert-Debré Hospital, AP-HP, Paris, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30417923

Citation

Bessis, D, et al. "Dermatological Manifestations in Noonan Syndrome: a Prospective Multicentric Study of 129 Patients Positive for Mutation." The British Journal of Dermatology, vol. 180, no. 6, 2019, pp. 1438-1448.
Bessis D, Miquel J, Bourrat E, et al. Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation. Br J Dermatol. 2019;180(6):1438-1448.
Bessis, D., Miquel, J., Bourrat, E., Chiaverini, C., Morice-Picard, F., Abadie, C., ... Cavé, H. (2019). Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation. The British Journal of Dermatology, 180(6), pp. 1438-1448. doi:10.1111/bjd.17404.
Bessis D, et al. Dermatological Manifestations in Noonan Syndrome: a Prospective Multicentric Study of 129 Patients Positive for Mutation. Br J Dermatol. 2019;180(6):1438-1448. PubMed PMID: 30417923.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation. AU - Bessis,D, AU - Miquel,J, AU - Bourrat,E, AU - Chiaverini,C, AU - Morice-Picard,F, AU - Abadie,C, AU - Manna,F, AU - Baumann,C, AU - Best,M, AU - Blanchet,P, AU - Bursztejn,A-C, AU - Capri,Y, AU - Coubes,C, AU - Giuliano,F, AU - Guillaumont,S, AU - Hadj-Rabia,S, AU - Jacquemont,M-L, AU - Jeandel,C, AU - Lacombe,D, AU - Mallet,S, AU - Mazereeuw-Hautier,J, AU - Molinari,N, AU - Pallure,V, AU - Pernet,C, AU - Philip,N, AU - Pinson,L, AU - Sarda,P, AU - Sigaudy,S, AU - Vial,Y, AU - Willems,M, AU - Geneviève,D, AU - Verloes,A, AU - Cavé,H, Y1 - 2019/01/18/ PY - 2018/10/27/accepted PY - 2018/11/13/pubmed PY - 2018/11/13/medline PY - 2018/11/13/entrez SP - 1438 EP - 1448 JF - The British journal of dermatology JO - Br. J. Dermatol. VL - 180 IS - 6 N2 - BACKGROUND: Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and are based on limited 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: Overall, 129 patients with NS were enrolled, including 65 patients with PTPN11-NS, 34 patients with PTPN11-NS with multiple lentigines (NSML), and 30 patients with NS who had a mutation other than PTPN11. Easy bruising was the most frequent dermatological finding in PTPN11-NS, present in 53·8% of patients. Multiple lentigines and café-au-lait macules (n ≥ 3) were present in 94% and 80% of cases of NSML linked to specific mutations of PTPN11, respectively. 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: The cutaneous phenotype of NS with a PTPN11 mutation is generally mild and nonspecific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities. SN - 1365-2133 UR - https://www.unboundmedicine.com/medline/citation/30417923/Dermatological_manifestations_in_Noonan_syndrome:_a_prospective_multicentric_study_of_129_patients_positive_for_mutation L2 - https://doi.org/10.1111/bjd.17404 DB - PRIME DP - Unbound Medicine ER -