Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is an autosomal dominant syndrome caused by heterozygous pathogenic germline variants in the fumarate hydratase (FH) gene. It is characterized by cutaneous and uterine leiomyomas and an increased risk of developing renal cell carcinoma (RCC), which is usually adult-onset. HLRCC-related RCC tends to be aggressive and can metastasize even when the primary tumor is small. Data on children and adolescents are scarce. Herein, we report two patients from unrelated Dutch families, with HLRCC-related RCC at the ages of 15 and 18 years, and a third patient with an FH mutation and complex renal cysts at the age of 13. Both RCC’s were localized and successfully resected, and careful MRI surveillance was initiated to monitor the renal cysts. One of the patients with RCC subsequently developed an ovarian Leydig cell tumor. A review of the literature identified 10 previously reported cases of HLRCC-related RCC in patients aged younger than 20 years, five of them presenting with metastatic disease. These data emphasize the importance of recognizing HLRCC in young patients to enable early detection of RCC, albeit rare. They support the recommendations from the 2014 consensus guideline, in which genetic testing for FH mutations, and renal MRI surveillance, is advised for HLRCC family members from the age of 8–10 years onwards.

中文翻译：

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年轻的FH突变携带者中的肾细胞癌：病例系列和文献综述。

遗传性平滑肌瘤病和肾细胞癌（HLRCC）是由富马酸水合酶（FH）基因中杂合的致病种系变异引起的常染色体显性综合征。它的特征是皮肤和子宫平滑肌瘤，以及发展成成人的肾细胞癌（RCC）的风险增加。与HLRCC相关的RCC倾向于具有侵略性，即使原发肿瘤很小也可以转移。关于儿童和青少年的数据很少。在此，我们报告了两名来自荷兰无关家庭的患者，他们患有HLRCC相关的RCC，年龄分别为15和18岁，第三名患有FH突变和复杂的肾囊肿在13岁时都定位并成功切除了两个RCC，并开始了仔细的MRI监视以监测肾囊肿。一名RCC患者随后患上了卵巢Leydig细胞瘤。文献综述确定了10例先前报道的20岁以下患者中与HLRCC相关的RCC病例，其中5例患有转移性疾病。这些数据强调了在年轻患者中识别HLRCC的重要性，以便尽早发现RCC（尽管很少见）。他们支持2014年共识指南中的建议，在该指南中，建议从8-10岁开始对HLRCC家庭成员进行FH突变的基因检测和肾脏MRI监测。