RET proto-oncogene testing in infants presenting with Hirschsprung disease identifies 2 new multiple endocrine neoplasia 2A kindreds.

BACKGROUND

Multiple endocrine neoplasia 2A (MEN 2A) is a genetic syndrome manifesting as medullary thyroid carcinoma (MTC), hyperparathyroidism, and pheochromocytoma. Multiple endocrine neoplasia 2A results from mutations in the RET proto-oncogene. Hirschsprung disease (HSCR) is a rare manifestation of MEN 2A and has been described in known MEN 2A families.

METHODS

Here we describe 2 MEN 2A families that were only identified after the diagnosis of HSCR.

RESULTS

Kindred 1: A boy presented in infancy with HSCR. Genetic screening revealed a C609Y mutation, which is consistent with MEN 2A. Evaluation of his sister, father, and grandmother revealed the same mutation. All 3 had thyroidectomies demonstrating C-cell hyperplasia. The grandmother had a microscopic focus of MTC. Kindred 2: An infant boy and his sister were diagnosed with HSCR as neonates. Genetic testing demonstrated a C620R gene mutation consistent with MEN 2A. Total thyroidectomies revealed metastatic MTC in the father and C-cell hyperplasia in both children.

CONCLUSIONS

Hirschsprung disease can be the initial presentation of MEN 2A. We strongly recommend that genetic screening be performed in patients presenting with HSCR, looking for the known RET mutations associated with MEN 2A. If a mutation consistent with MEN 2A is detected, genetic screening of all first-degree relatives in the kindred is recommended.