A La Greca, D Dawes, M Albuja-Cruz, C Raeburn, L Axell, L Ku, C Klein, C Marshall, L Fishbein
{"title":"一个家族的 MEN2 表型与种系杂合子罕见 RET K666N 变异有关。","authors":"A La Greca, D Dawes, M Albuja-Cruz, C Raeburn, L Axell, L Ku, C Klein, C Marshall, L Fishbein","doi":"10.1530/EDM-24-0009","DOIUrl":null,"url":null,"abstract":"<p><strong>Summary: </strong>Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by germline-activating pathogenic variants in the RET proto-oncogene. MEN2A is the most common subtype, with a risk for medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT), whereas MEN2B is less common and associated with MTC and PHEO along with mucosal neuromas. Little is known about the specific RET germline heterozygous variant K666N. This variant has been described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. There is one case of MTC and bilateral PHEO. The RET K666N variant is not stratified yet by the American Thyroid Association, and data are limited on pathogenicity; therefore, appropriate screening and treatment of asymptomatic RET K666N carriers are unclear. Here, we report a family with a heterozygous germline RET K666N variant. The proband was identified when she experienced cardiogenic shock and multi-organ failure after an elective hysterectomy and subsequently was found to have PHEO, with genetic testing revealing the RET K666N germline variant. Patient consent was obtained through IRB protocol COMIRB #15-0516.</p><p><strong>Learning points: </strong>The specific RET germline heterozygous variant K666N is rare and described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. Our proband is much younger and has PHEO, MTC, and PHPT. The RET K666N germline variant appears to be a low penetrance variant for MEN2.</p>","PeriodicalId":37467,"journal":{"name":"Endocrinology, Diabetes and Metabolism Case Reports","volume":null,"pages":null},"PeriodicalIF":0.7000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378119/pdf/","citationCount":"0","resultStr":"{\"title\":\"MEN2 phenotype in a family with germline heterozygous rare RET K666N variant.\",\"authors\":\"A La Greca, D Dawes, M Albuja-Cruz, C Raeburn, L Axell, L Ku, C Klein, C Marshall, L Fishbein\",\"doi\":\"10.1530/EDM-24-0009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Summary: </strong>Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by germline-activating pathogenic variants in the RET proto-oncogene. MEN2A is the most common subtype, with a risk for medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT), whereas MEN2B is less common and associated with MTC and PHEO along with mucosal neuromas. Little is known about the specific RET germline heterozygous variant K666N. This variant has been described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. There is one case of MTC and bilateral PHEO. The RET K666N variant is not stratified yet by the American Thyroid Association, and data are limited on pathogenicity; therefore, appropriate screening and treatment of asymptomatic RET K666N carriers are unclear. Here, we report a family with a heterozygous germline RET K666N variant. The proband was identified when she experienced cardiogenic shock and multi-organ failure after an elective hysterectomy and subsequently was found to have PHEO, with genetic testing revealing the RET K666N germline variant. Patient consent was obtained through IRB protocol COMIRB #15-0516.</p><p><strong>Learning points: </strong>The specific RET germline heterozygous variant K666N is rare and described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. Our proband is much younger and has PHEO, MTC, and PHPT. The RET K666N germline variant appears to be a low penetrance variant for MEN2.</p>\",\"PeriodicalId\":37467,\"journal\":{\"name\":\"Endocrinology, Diabetes and Metabolism Case Reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.7000,\"publicationDate\":\"2024-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378119/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Endocrinology, Diabetes and Metabolism Case Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1530/EDM-24-0009\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"Q4\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrinology, Diabetes and Metabolism Case Reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1530/EDM-24-0009","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/1 0:00:00","PubModel":"Print","JCR":"Q4","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
MEN2 phenotype in a family with germline heterozygous rare RET K666N variant.
Summary: Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by germline-activating pathogenic variants in the RET proto-oncogene. MEN2A is the most common subtype, with a risk for medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT), whereas MEN2B is less common and associated with MTC and PHEO along with mucosal neuromas. Little is known about the specific RET germline heterozygous variant K666N. This variant has been described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. There is one case of MTC and bilateral PHEO. The RET K666N variant is not stratified yet by the American Thyroid Association, and data are limited on pathogenicity; therefore, appropriate screening and treatment of asymptomatic RET K666N carriers are unclear. Here, we report a family with a heterozygous germline RET K666N variant. The proband was identified when she experienced cardiogenic shock and multi-organ failure after an elective hysterectomy and subsequently was found to have PHEO, with genetic testing revealing the RET K666N germline variant. Patient consent was obtained through IRB protocol COMIRB #15-0516.
Learning points: The specific RET germline heterozygous variant K666N is rare and described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. Our proband is much younger and has PHEO, MTC, and PHPT. The RET K666N germline variant appears to be a low penetrance variant for MEN2.
期刊介绍:
Endocrinology, Diabetes & Metabolism Case Reports publishes case reports on common and rare conditions in all areas of clinical endocrinology, diabetes and metabolism. Articles should include clear learning points which readers can use to inform medical education or clinical practice. The types of cases of interest to Endocrinology, Diabetes & Metabolism Case Reports include: -Insight into disease pathogenesis or mechanism of therapy - Novel diagnostic procedure - Novel treatment - Unique/unexpected symptoms or presentations of a disease - New disease or syndrome: presentations/diagnosis/management - Unusual effects of medical treatment - Error in diagnosis/pitfalls and caveats