Multiple endocrine neoplasia type 2 (MEN2) is a dominantly inherited condition with defined correlations between the genetic variant and clinical presentations. The location of pathogenic variants in the RET gene is a significant determinant of disease presentation and is associated with variable gene activation. Heterozygous pathogenic variants in codon 634 result in earlier onset of medullary thyroid carcinoma and higher incidence of phaeochromocytoma. Here we describe a consanguineous family with MEN2A that includes two children homozygous for the established pathogenic variant p. Cys634Trp. Both parents and a sibling were confirmed to being heterozygotes. Previous reports of biallelic or multiple RET variants have been limited to weakly activating variants. We present the first report of individuals homozygous for the highly activating RET p. Cys634Trp pathogenic variant and discuss disease severity and onset in this rare occurrence.

2型多发性内分泌肿瘤（MEN2）是遗传性疾病，在遗传变异和临床表现之间具有明确的相关性。RET基因中致病变异的位置是疾病表现的重要决定因素，并且与可变基因激活相关。634密码子的杂合致病变体导致甲状腺髓样癌的早期发作和嗜铬细胞瘤的发生率更高。在这里，我们描述了一个MEN2A的近亲家庭，其中包括两个为确定的致病性变体p纯合的孩子。Cys634Trp。父母和同胞均被确认为杂合子。以前有关双等位基因或多种RET的报道变体仅限于弱激活变体。我们提出了高度激活的RET p纯合的个体的第一个报告。Cys634Trp致病变异，并讨论这种罕见情况下的疾病严重程度和发作。