Background: Germline missense mutations of the RET protooncogene cause a clinical spectrum called multiple endocrine neoplasia (MEN) type 2. A strong genotype-phenotype correlation results in major implications for the clinical approach. More information on less common mutations is needed to advance specific guidance. Patients and Methods: We report individualized patient information on 36 carriers of the intracellular RET gene mutation S891A from three centers and clustered data of 38 former patients reported in the literature in nine additional studies. Results: S891A mutation accounts for up to 5% of all patients to date reported with RET mutations and 16% of those hitherto reported with intracellular mutations. S891A mutation caused medullary thyroid cancer (MTC) in 69.4%, pheochromocytoma in 2.8%, and parathyroid hyperplasia in 8.3% of the 36 patients of this case series and in 63.5, 4.1, and 4.1%, respectively, for the entire groups of 74 patients. The youngest age of onset for MTC in this group was 17 yr (median, 46 yr; range, 17-80 yr), for pheochromocytoma 46 yr (median, 46 yr), and for parathyroid hyperplasia 17 yr (median, 20 yr, range, 17-46 yr). Persistence of MTC was described in 14.3% of patients with available follow-up. Additional findings included corneal nerve thickening in three of 74 patients (4.1%). Conclusion: This intracellular mutation can initiate the full spectrum of MEN2a, initiates MTC at an early age, and causes recurrence and death if undertreated. We recommend stringent adherence to established guidance in MEN2a in this rare mutation.
The clinical spectrum of multiple endocrine neoplasia type 2a caused by the rare intracellular RET mutation S891A / K.M. Schulte, A. Machens, L. Fugazzola, A. McGregor, S. Diaz Cano, L. Izatt, S. Aylwin, N. Talat, P. Beck Peccoz, H. Dralle. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - 95:9(2010 Sep), pp. E92-E97.
|Titolo:||The clinical spectrum of multiple endocrine neoplasia type 2a caused by the rare intracellular RET mutation S891A|
BECK PECCOZ, PAOLO LUIGI MARIA (Penultimo)
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
|Data di pubblicazione:||set-2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1210/jc.2010-0375|
|Appare nelle tipologie:||01 - Articolo su periodico|