医学
外显率
内科学
多发性内分泌肿瘤2型
预测性试验
队列
回顾性队列研究
多发性内分泌肿瘤
原发性甲状旁腺功能亢进
疾病
甲状腺癌
肿瘤科
甲状腺
胃肠病学
种系突变
突变
遗传学
表型
基因
生物
作者
Axelle Vuylsteke,Laurens Hannes,Hilde Brems,Koen Devis,Marleen Renard,Anne Uyttebroeck,Eric Legius,Brigitte Decallonne
出处
期刊:European journal of endocrinology
[Bioscientifica]
日期:2023-09-01
卷期号:189 (3): 402-408
标识
DOI:10.1093/ejendo/lvad126
摘要
The c.1998delinsTTCT variant in the RET gene (codon 666) is linked to medullary thyroid carcinoma in Belgium. We aimed to study the clinical phenotype and the age-dependent penetrance in predictive variant carriers.Retrospective study of index patients and predictive variant carriers, identified through familial cascade testing between 2001 and 2020.The total cohort comprised 119 patients: 15 index patients, 102 heterozygous, and 2 homozygous predictive variant carriers. Among heterozygous carriers, high suspicion of clinical disease was present in 25 patients at initial evaluation and in 3 patients during follow-up. No high suspicion of clinical disease was observed during surveillance in 56 patients, and 18 patients did not proceed to screening for clinical disease. Compared to index patients, surgically treated heterozygous predictive variant carriers had a lower presurgical basal calcitonin, a lower disease stage, less need for adjuvant therapy, and higher chances of remission. In heterozygous carriers, median age at developing high suspicion of disease is 52 years (range 7-75), with a predicted penetrance of 62% (9% SE) at the age of 70 years. Two patients were identified with pheochromocytoma and 1 patient with primary hyperparathyroidism. The 2 homozygous predictive variant carriers presented with higher disease severity at first clinical evaluation.The c.1998delinsTTCT variant in the RET gene is pathogenic and associated with a moderate risk for medullary thyroid carcinoma and rarely with other multiple endocrine neoplasia type 2A (MEN2A) manifestations. Active surveillance is a possible option in heterozygous gene carriers with a negative first clinical evaluation.
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