Identification of three clinical neurofibromatosis 1 subtypes: Latent class analysis of a series of 1351 patients. (1st March 2022)

• Record Type: Journal Article
• Authors: Bergqvist, C.; Fertitta, L.; Ezzedine, K.; Jannic, A.; Zehou, O.; Ferkal, S.; Combemale, P.; Barbarot, S.; Mazereeuw‐Hautier, J.; Sbidian, E.; Wolkenstein, P.
• Other Names: Adamski Henri investigator.; Baumann‐Morel Clarisse investigator.; Bellanné Christine investigator.; Bieth Eric investigator.; Bousquet Pascal investigator.; Brandt Christian investigator.; Balguerie Xavier investigator.; Castelnau Pierre investigator.; Chaix Yves investigator.; Chevrant‐Breton Jacqueline investigator.; Collet Evelyne investigator.; Cuny Jean‐François investigator.; Chastagner Pascal investigator.; Chandeclerc Marie‐Lorraine investigator.; Cheuret Emmanuel investigator.; Cintas Pascal investigator.; Dollfus Helene investigator.; Derancourt Christian investigator.; Drouin‐Garraud Valérie investigator.; d'Incan Michel investigator.; De Leersnyder Hélène investigator.; Dereure Olivier investigator.; Doumar Diane investigator.; Fabre Nicolas investigator.; Ferraro Vincenza investigator.; Francannet Christine investigator.; Faivre Laurence investigator.; Fellmann Florence investigator.; Feugier Nathalie investigator.; Gaillard Dominique investigator.; Goldenberg Alice investigator.; Guyant‐Marechal Lucie investigator.; Guillot Bernard investigator.; Guillamo Jean‐Sebastien investigator.; Hadj‐Rabia Smaïl investigator.; Hamel‐Teillac Dominique investigator.; Kemlin Isabelle investigator.; Lacour Jean‐Philippe investigator.; Laithier Veronique investigator.; Lesavre Nathalie investigator.; Lyonnet Stanislas investigator.; Maincent Kim investigator.; Maradeix Sophie investigator.; Machet Laurent investigator.; Mansat Eva investigator.; Meyer Nicolas investigator.; Mozelle Monique investigator.; Celine Moret Jean Christophe Moreno investigator.; Puzenat Eric investigator.; Parfait Béatrice investigator.; Pinson Stéphane investigator.; Pasmant Eric investigator.; Rodriguez Diana investigator.; Stalder Jean‐François investigator.; Schweitzer Elisabeth investigator.; Thalamas Claire investigator.; Thauvin Christel investigator.; Vidaud Dominique investigator.; Vidaud Michel investigator.; Verloes Alain investigator.; Zeller Jacques investigator.;
• Is Part Of: Journal of the European Academy of Dermatology and Venereology. Volume 36:Number 5(2022)
• Page Start: 739
• Page End: 743
• Publication Date: 2022-03-01
• Subjects: Dermatology -- Periodicals; Sexually transmitted diseases -- Periodicals; 616.5
• DOI: 10.1111/jdv.17974
• Languages: English
• ISSNs: 0926-9959

Abstract

Abstract: Background: Neurofibromatosis 1 (NF1) is one of the most common inherited disorders characterized by mutations in the tumour suppressor gene NF1 . Its clinical manifestations are highly variable and unpredictable. A specific NF1 mutation does not predict the severity or complications of the disease. Objective: The objective of this study was to build an empirical classification scheme without any a priori hypotheses to identify the underlying NF1 subtypes that best explain the observed heterogeneity. Methods: We performed latent class analysis (LCA) of 1351 consecutive NF1 patients aged >17 years seen between 2002 and 2014. Data and phenotypic features were collected prospectively on a standardized form. Results: The median age was 36.8 (17–81) years. A three‐class model showed the best fit: 706 (52%) belonged to the LC1 'Cutaneous neurofibromas' class having preferentially cutaneous neurofibromas (99%), plexiform neurofibromas (63%) and blue‐red macules (29%); 593 (44%) belonged to the LC2 'Subcutaneous neurofibromas' class characterized by the presence of at least 10 subcutaneous neurofibromas (21%) and a familial form (77%) and 52 (4%) belonged to the LC3 'Dysmorphic phenotype' class characterized by dysmorphic features (78%) and learning difficulties (87%). Patients in LC1 had a higher likelihood of developing scoliosis (RR = 1.7, 95% confidence interval (CI) [1.2–2.4]). Patients in LC2 were more likely to be men (RR = 1.4, 95% CI [1.1–1.7]). Patients in LC3 were at higher risk of having an optic pathway glioma (RR = 4.8, 95% CI [1.9–11.8]) and epilepsy (RR = 4.5, 95% CI [1.8–11.6]). Conclusion: Our findings invite the performance of a larger cohort study to test whether the various latent classes reflect different underlying genetic modifiers of these phenotypic traits.