Orrego John J, Chorny Joseph A
Endocrinol Diabetes Metab Case Rep. 2024 Dec 20;2024(4). doi: 10.1530/EDM-24-0073. Print 2024 Oct 1.
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition characterized by multiple cutaneous and uterine leiomyomas and renal cell cancer (RCC). HLRCC is caused by germline pathogenic/likely pathogenic (P/LP) variants in the fumarate hydratase (FH) gene on chromosome 1q42.3, encoding the mitochondrial enzyme responsible for the conversion of fumarate to malate in the Krebs cycle. 0.6-3.1% of individuals with pheochromocytoma/paraganglioma (PCC/PGL) carry a germline variant in the FH gene. Most of these patients have no personal or family history of HLRCC-associated manifestations, but some of them do. We described a female-to-male transgender with HLRCC who presented with large symptomatic uterine leiomyomas in the third decade of life and was diagnosed with a PCC 19 years after hysterectomy and with cutaneous leiomyomas and an aggressive form of RCC in the sixth decade of life. With the publication of this case and the review of the existent literature, and until more information becomes available, we would like to emphasize that clinicians should be aware of the possible connection between HLRCC and PCC/PGL, that genetic testing for susceptibly genes for PCC/PGL should include the FH gene and finally that patients with HLRCC should be screened for PCC/PGL.
HLRCC, an autosomal dominant condition caused by germline P/LP variants in the fumarate hydratase (FH) gene, is characterized by multiple cutaneous and uterine leiomyomas and RCC.0.6-3.1% of individuals with PCC/PGL carry a germline P/LP variant in the FH gene.Most of these patients have no personal or family history of HLRCC-associated manifestations, but some of them do.Preliminary evidence suggests that genetic testing for susceptibly genes for PCC/PGL should include the FH gene and that patients with HLRCC should be screened for PCC/PGL.Until more information becomes available, we suggest doing a full history, physical, family history, and screen for HLRCC-associated manifestations when there is an FH variant.Screening for PCC/PGL in patients with HLRCC could potentially include a baseline whole-body MRI and plasma fractionated metanephrines.
遗传性平滑肌瘤病和肾细胞癌（HLRCC）是一种常染色体显性疾病，其特征为多发性皮肤和子宫平滑肌瘤以及肾细胞癌（RCC）。HLRCC由位于1q42.3染色体上的延胡索酸水合酶（FH）基因的种系致病性/可能致病性（P/LP）变异引起，该基因编码负责在三羧酸循环中将延胡索酸转化为苹果酸的线粒体酶。0.6% - 3.1%的嗜铬细胞瘤/副神经节瘤（PCC/PGL）患者携带FH基因的种系变异。这些患者中的大多数没有HLRCC相关表现的个人或家族史，但其中一些人有。我们描述了一名患有HLRCC的女性向男性 transgender 患者，该患者在30岁时出现有症状的大型子宫平滑肌瘤，子宫切除术后19年被诊断为PCC，在60岁时被诊断为皮肤平滑肌瘤和侵袭性RCC。随着该病例的发表以及对现有文献的回顾，在获得更多信息之前，我们想强调临床医生应意识到HLRCC与PCC/PGL之间的可能联系，PCC/PGL易感基因的基因检测应包括FH基因，最后HLRCC患者应接受PCC/PGL筛查。
HLRCC是一种由延胡索酸水合酶（FH）基因的种系P/LP变异引起的常染色体显性疾病，其特征为多发性皮肤和子宫平滑肌瘤以及RCC。0.6% - 3.1%的PCC/PGL患者携带FH基因的种系P/LP变异。这些患者中的大多数没有HLRCC相关表现的个人或家族史，但其中一些人有。初步证据表明，PCC/PGL易感基因的基因检测应包括FH基因，HLRCC患者应接受PCC/PGL筛查。在获得更多信息之前，我们建议当存在FH变异时，进行全面的病史、体格检查、家族史检查以及HLRCC相关表现的筛查。对HLRCC患者进行PCC/PGL筛查可能包括基线全身MRI和血浆分馏甲氧基肾上腺素检测。
