Cutaneous lesions and other non-endocrine manifestations of Multiple Endocrine Neoplasia type 1 syndrome.

Background: Multiple Endocrine Neoplasia type 1 is a rare genetic syndrome mainly caused by mutations of gene and characterized by a combination of several endocrine and non-endocrine manifestations. The objective of this study was to describe cutaneous lesions and other non-endocrine manifestations of in a cohort of patients with familial (F) and sporadic (S) , compare the prevalence of these manifestations between the two cohorts, and investigate the correlation with mutation status.

Methods: We collected phenotypic and genotypic data of 185 patients with F- and S- followed from 1997 to 2022. The associations between F- and S- or mutation-positive and mutation-negative patients and non-endocrine manifestations were determined using chi-square or Fisher's exact tests or multivariate exact logistic regression analyses.

Results: The prevalence of angiofibromas was significantly higher in F- than in S- in both the whole (p < 0.001) and index case (p = 0.003) cohorts. The prevalence of lipomas was also significantly higher in F- than in S- (p = 0.009) and in mutation-positive than in mutation-negative (p = 0.01) index cases. In the whole cohort, the prevalence of lipomas was significantly higher in mutation-positive compared to mutation-negative patients (OR = 2.7, p = 0.02) and in F- than in S- (p = 0.03), only after adjustment for age. No significant differences were observed for the other non-endocrine manifestations between the two cohorts. Hibernoma and collagenoma were each present in one patient (0.5%) and meningioma and neuroblastoma in 2.7% and 0.5%, respectively. Gastric leiomyoma was present in 1.1% of the patients and uterine leiomyoma in 14% of women. Thyroid cancer, breast cancer, lung cancer, basal cell carcinoma, melanoma, and colorectal cancer were present in 4.9%, 2.7%, 1.6%, 1.6%, 2.2%, and 0.5% of the whole series, respectively.

Conclusions: We found a significantly higher prevalence of angiofibromas and lipomas in F- compared with S- and in mutation-positive compared to mutation-negative patients. In patients with one major endocrine manifestation of , the presence of cutaneous lesions might suggest the diagnosis of and a possible indication for genetic screening.