ESPE Abstracts

Purpose: Multiple endocrine neoplasia (MEN) is a rare, autosomal dominantly inherited cancer syndrome caused by a mutation in MEN1 or RET gene. Identification of the genetic causes of the MEN is critical because genotype provides information on timing of prophylactic surgery in patients with MEN type 2 who have clinically silent tumors. Therefore, this study investigated clinical phenotype and molecular characteristics of children with MEN in a single academic center.

Method: This study included eight children with MEN from seven unrelated families who were diagnosed prior to the age of 18 years between March 2008 and March 2019. Clinical and endocrine characteristics were analyzed by retrospective chart review. Molecular analysis of the MEN1 or RET gene was performed according to the clinical phenotype and family history.

Results: Eight patients from seven families were genetically confirmed with MEN, including MEN type 1 (n = 1), MEN type 2A (n = 6), and MEN type 2B (n = 1). Seven patients had family members with MEN, while only one patient with MEN type 2B occurred sporadically by a de novo mutation in RET. A 10-year-old girl presented with hypoglycemia due to pancreatic insulinoma, and finally diagnosed with MEN type 1. The patient harbored a known heterozygous mutation of c.852-2A>G in MEN1, which was inherited from her father. A 6-year-old boy with MEN type 2B initially manifested tongue neuroma and underwent prophylactic thyroidectomy because of the highest risk mutation at codon 918 in RET. Six patients with MEN type 2A had family members of mutation in RET and were diagnosed by genetic screening during asymptomatic period. A heterozygous mutation at 634th codon was identified in unrelated 4 families with MEN type 2A: c.1900T>C (p.C634R) in 3 families and c.1901G>A (p.C634Y) in one family. The remaining one patient with MEN type 2A harbored a heterozygous mutation of c.1891G>T (p.D631Y) in RET. Three children underwent prophylactic thyroidectomy, and the other patients with RET p.C634R mutation were recommended to undergo prophylactic thyroidectomy.

Conclusions: The RET gene mutation at codon 634 was the most prevalent in our patients. Genetic screening should be considered in children with family history of MEN for early diagnosis and treatment of hereditary endocrine tumors. Patients with any of the genetic syndromes require lifelong tumor surveillance to facilitate early tumor detection and treatment of associated neoplasms.