Endocrine Abstracts

JOINT1683

Introduction: DICER1 syndrome (DS) is a genetic condition that predisposes individuals to benign and malignant neoplasms. It is caused by pathogenic variants of the DICER1 gene, inherited in an autosomal dominant manner, with low penetrance. The DICER1 protein promotes the maturation of microRNAs, which regulate post-transcriptional mRNA expression.

Objective: To describe the clinical, biochemical and genetic characteristics of a group of pediatric patients with DS diagnosed and followed in the endocrine service at a single tertiary center

Methods: A retrospective descriptive study was conducted. Molecular studies consisted of exonic sequencing of the DICER1 gene in peripheral blood leukocytes and tumor tissue. The variables analyzed were: age at diagnosis, sex, inheritance, associated pathology, and clinical characteristics of endocrine involvement.

Results: Seventeen patients were included, 12 girls (70%). The median age was 13. 8 years (range 1. 9-16. 2). The median follow-up time was 3 years (IQR 0. 67-5). Sixteen patients had pathogenic variants in the germline (94%). The family study was performed in 14 patients, of which 10/7 families were hereditary and 4 were de novo. The associated pathologies were: thyroid gland involvement (n = 16; 94%), ovarian Sertoli-Leydig cell tumor (n = 5; 29%), uterine cervical rhabdomyosarcoma (n = 3; 18%), cystic nephroma (n = 3; 18%), anaplastic renal sarcoma (n = 1; 6%), pulmonary cyst (n = 1; 6%), lymph node sarcoidosis (n = 1; 6%) Regarding thyroid pathology, the first clinical manifestations were: cervical mass (n = 10; 62. 5%) and ultrasound finding (n = 6; 37. 5%). The histological diagnoses were: multinodular goiter (MNG) (n = 13; 81. 2%), papillary thyroid carcinoma, follicular subtype (n = 5; 31. 2%), and follicular adenoma (n = 2; 12. 5%). All patients had normal thyroid function and negative antithyroid antibodies. Regarding ovarian Sertoli-Leydig cell tumors, the clinical manifestations in prepubertal patients (n = 2) were abdominal distension and mass, and in pubertal patients (n = 3), menstrual cycle alteration (n = 3) and clinical-biochemical signs of virilization (n = 1). Histology in prepubertal patients was undifferentiated, and in pubertal patients, it was moderately differentiated. In 4 cases, the location was unilateral. All with associated thyroid pathology. Uterine rhabdomyosarcoma presented with gynecological bleeding (n = 3) and was associated with Sertoli-Leydig cell tumor (n = 1) and thyroid pathology (n = 3).

Discussion: According to the literature, DS presented during childhood and adolescence, with predominance in girls and a familial inheritance pattern. Thyroid involvement was the most frequent. Sertoli-Leydig cell tumors in prepubertal patients showed histological features of worse prognosis. Lymph node sarcoidosis was not previously reported in association with DS. The diagnosis of DS is crucial for patient follow- up and detection of affected family members.