Cardiac myxoma caused by fumarate hydratase gene deletion in patient with cortisol-secreting adrenocortical adenoma

Kentaro Suda, Hidenori Fukuoka, Yuto Yamazaki, Katsumi Shigemura, Miki Mukai, Yukiko Odake, Ryusaku Matsumoto, Hironori Bando, Michiko Takahashi, Genzo Iguchi, Masato Fujisawa, Masahiro Oka, Katsuhiko Ono, Kazuo Chihara, Hironobu Sasano, Wataru Ogawa, Yutaka Takahashi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Context: Germline mutations in fumarate hydratase (FH) gene are known to cause hereditaryleiomyomatosis and renal cell carcinoma (HLRCC) and are occasionally accompanied withcutaneous and uterine leiomyoma or cortisol-producing adrenocortical hyperplasia. However,the association between FH mutations and cardiac or adrenocortical tumors has remainedunknown. Here, we identified a novel deletion in FH, exhibiting cardiac myxoma and subclinicalCushing syndrome due to adrenocortical tumor.Case Description: A 44-year-old man was referred to our hospital for cardiac and adrenaltumor evaluation. He had a history of multiple painful, dermal papules and nodules diagnosedas cutaneous leiomyoma. The surgically resected cardiac tumor was diagnosed as myxoma.The adrenal tumor was clinically diagnosed as subclinical Cushing syndrome. Laparoscopicallyresected adrenal tumor was pathologically diagnosed as adrenocortical adenoma harboringunique histological findings similar to primary pigmented nodular adrenocortical disease(PPNAD). DNA analysis revealed a germline deletion in FH c0.737delT (p. Phe225Leufs*31)and loss of heterozygosity (LOH) in cardiac myxoma. As a functional analysis of FH in cardiacmyxoma, low FH protein expression with elevated 2-succinocysteine (2SC), a marker of FHdysfunction, was immunohistochemically detected. However, in adrenocortical tumor, LOH of FHwas not detected, and FH or 2SC expression was not altered.Conclusions: This is the first case of HLRCC complicated by cardiac myxoma. LOH of FH deletionand its dysfunction were identified in cardiac myxoma. The association between FH deletion andadrenocortical lesion, however, needs to be further clarified.

Original languageEnglish
Pages (from-to)1957-1962
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Issue number6
Publication statusPublished - 2020 Jun 1


  • Adrenocortical tumor
  • Cardiac myxoma
  • Fumarate hydratase
  • Gene mutation


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