A homozygous RET K666N genotype with an MEN2A phenotype.

A homozygous RET K666N genotype with an MEN2A phenotype.

J Clin Endocrinol Metab. 2018 Feb 02;:

Authors: Jaber T, Hyde SM, Cote GJ, Grubbs EG, Giles WH, Stevens CA, Dadu R

Abstract
Context: Germline RET K666N mutation has been described as a pathogenic mutation with low disease penetrance for medullary thyroid cancer (MTC) without other features of MEN2A. We describe a patient with homozygous RET K666N mutation with MTC and bilateral pheochromocytoma (PHEO).
Case Description: A 59-year-old female was diagnosed with MTC after biopsy of two thyroid nodules. Coincident biochemical and radiologic testing was suspicious for bilateral PHEO, confirmed after bilateral adrenalectomy. There was no evidence for primary hyperparathyroidism (PHPT). She had a total thyroidectomy with neck dissection revealing bilateral MTC with lymph node metastases. Germline RET testing identified homozygous K666N mutations. Genetic testing of family members expectedly showed that both adult children harbor a heterozygous K666N mutation. Her 32-year-old son had an elevated calcitonin level and underwent thyroidectomy which identified MTC. Her 30-year-old daughter had a normal calcitonin level. Prophylactic thyroidectomy showed C-cell hyperplasia only. Three of seven other family members were tested and found to carry the mutation. All had normal calcitonin levels and none had biochemical evidence for PHEO or PHPT. Given the absence of PHEO in reported RET K666N families, our proband underwent genetic testing for causes of hereditary paragangliomas/PHEO. No additional mutations were identified.
Conclusions: This is the first reported case of a homozygous RET K666N mutation leading to coincident MTC and PHEO. Heterozygous presentation of RET K666N mutations have low penetrance for isolated MTC. We believe that the gene dosage associated with the homozygosity of this variant contributed to the occurrence of bilateral PHEO.

PMID: 29408964 [PubMed - as supplied by publisher]

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