title: RET germline mutation in codon 791 in a family representing 3 generations from age 5 to age 70 years: should thyroidectomy be performed?
abstract: OBJECTIVE
  To describe a kindred with a rare RET germline mutation in codon 791 and discuss potential management strategies.
  
  
  METHODS
  We present clinical and biochemical data as well as results of mutation analysis in our study subjects and provide an overview of related published reports.
  
  
  RESULTS
  Multiple endocrine neoplasia type 2 (MEN 2) is a familial cancer syndrome characterized by the development of medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia or adenoma. Germline mutations in RET are responsible for this autosomal dominant syndrome. Familial MTC is a variant of MEN 2A and can be caused by RET mutations in codon 791. Deaths from gene carriers with mutations in these codons have not yet been reported. In general, gene carriers with these RET mutations have late-onset MTC. Because only a few kindreds with this specific mutation have been identified and no long-term follow-up data are available, management of these patients can be a challenge. We illustrate the difficulties with decisions about not only when to perform thyroidectomy in these patients but also whether thyroidectomy should even be considered in such gene carriers with a benign course. Our reported kindred included four carriers with a codon 791 RET germline mutation, one of whom had the rare concomitant occurrence of acromegaly and MEN 2A. The 70-year-old mother had acromegaly and hyperparathyroidism but normal serum calcitonin levels and normal findings on thyroid ultrasound examination. She refused pentagastrin testing and any surgical intervention. The 37-year-old daughter had hypothyroidism, a small thyroid gland, and negative results of pentagastrin stimulation testing of calcitonin. The 18-year-old grandson also had a negative pentagastrin test result and normal thyroid ultrasound findings. The 5-year-old granddaughter had normal results of thyroid ultrasonography. In all patients, we recommended thyroidectomy.
  
  
  CONCLUSIONS
  Prospective studies are needed to clarify which patients with codon 791 RET germline mutation should undergo thyroidectomy.
authors.affiliation: Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
authors.forename: Volker F H
authors.initials: VF
authors.lastname: Brauer
authors.forename: Gerhard H
authors.initials: GH
authors.lastname: Scholz
authors.forename: Susanne
authors.initials: S
authors.lastname: Neumann
authors.forename: Tobias
authors.initials: T
authors.lastname: Lohmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Paschke
authors.forename: Christian A
authors.initials: CA
authors.lastname: Koch
mesh_terms: D000172:Acromegaly / Q000150:complications; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003062:Codon; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D018813:Multiple Endocrine Neoplasia Type 2a / Q000150:complications / Q000235:genetics* / Q000601:surgery*; D015513:Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013965:Thyroidectomy
chemical_list: D003062:Codon; D015513:Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases