Carney triad can be (rarely) associated with germline succinate dehydrogenase defects

  title={Carney triad can be (rarely) associated with germline succinate dehydrogenase defects},
  author={Sosipatros Alexandros Boikos and Paraskevi Xekouki and Elena Fumagalli and Fabio Rueda Faucz and Margarita J Raygada and Eva Szarek and Evan R. Ball and S. Y. Kim and Markku Miettinen and Lee J Helman and J. Aidan Carney and Karel Pacak and Constantine A. Stratakis},
  journal={European Journal of Human Genetics},
Carney triad, the association of paragangliomas/pheochromocytomas, gastrointestinal stromal tumors and pulmonary chondromas, is a sporadic condition that is significantly more frequent in females; its genetic etiology remains unknown. Carney triad is distinct from the dyad of paragangliomas/pheochromocytomas and gastrointestinal stromal tumors, known as Carney–Stratakis syndrome, which is inherited in an autosomal- dominant manner and is almost always caused by succinate dehydrogenase subunit… 

A case of Carney triad complicated by renal cell carcinoma and a germline SDHA pathogenic variant

This is the first reported case of an SDHA pathogenic variant in a patient with Carney triad complicated by RCC, and it is likely indicated the SDHA variant would not be causative of the R CC, but could still predispose to the development of neoplasias.

SDHC Methylation Pattern in Patients With Carney Triad

The finding of SDHC promoter hypermethylation in the non-neoplastic gastric wall favors the hypothesis of postzygotic somatic mosaicism as the biological background of Carney triad, and offers an explanation of the multifocality of gastrointestinal stromal tumors of the stomach occurring in this scenario.

The Case of the Index Patient of Carney Triad: A Clinical Puzzle With an Epigenetic Solution

The index patient of the syndrome recently died of the disorder 50 years after resection of her first tumor, and the etiology of Carney triad, which had defied elucidation, was finally emerging.

Carney’s triad in an adult male from a tertiary care center in India: a case report

This report aims to highlight the various manifestations of Carney’s triad with emphasis on management of wild-type succinate-dehydrogenase-deficient gastrointestinal stromal tumor and proposes more conservative modalities of resection.

Pheochromocytoma and paraganglioma: implications of germline mutation investigation for treatment, screening, and surveillance.

PGL/PCC are more commonly associated with a germline mutation than any other cancer type, therefore, all individuals with these types of tumors should undergo genetic risk evaluation.

Conventional Risk Stratification Fails to Predict Progression of Succinate Dehydrogenase–deficient Gastrointestinal Stromal Tumors: A Clinicopathologic Study of 76 Cases

SDH-deficient GISTs account for approximately 8% of gastrointestinal stromal tumors and are associated with a high rate of distant metastasis, regardless of conventional risk category.

Gastrointestinal stromal tumors caused by novel germline variants in SDHB and KIT: a report of two cases and literature review

These cases highlight the diverse clinical presentations of patients with germline variants and raise several important points about the diagnosis and management of these patients, in particular: mutation in the SDH family of genes should be suspected in KIT and PDGFRA wild-type tumors; germline testing should be considered in patients with multiple GISTs or those who present with disease at a young age.

Germline c.1A>C heterozygous pathogenic variant in SDHA reported for the first time in a young adult with a gastric gastrointestinal stromal tumour (GIST): a case report

All patients diagnosed with WT GISTs should be referred to a hereditary cancer genetic counseling unit regardless of the age at presentation or the absence of a suspicious family history, as this is the first published report in which the c.1A > C; p.(Met1?) pathogenic variant in the SDHA is associated with a GIST.



The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney–Stratakis syndrome): molecular genetics and clinical implications

The findings were consistent with a common genetic aetiology of these two tumours in CT, and have clinical implications for patients with GISTs that are cKIT‐ and PDGFRA‐mutation negative: these tumours are usually resistant to treatment with currently available tyrosine kinase inhibitors and may be part of a syndrome such as CT or CSS.

Carney triad versus Carney Stratakis syndrome: two cases which illustrate the difficulty in distinguishing between these conditions in individual patients

The difficulty in distinguishing between Carney triad and Carney Stratakis syndrome due to the rarity of the individual components makes it difficult to differentiate confidently between the two conditions.

Genetics of carney triad: recurrent losses at chromosome 1 but lack of germline mutations in genes associated with paragangliomas and gastrointestinal stromal tumors.

Investigating the possibility that patients with CT and/or their tumors may harbor mutations of the SDHB, SDHC, SDHD, KIT, and PDGFRA genes and identifying any other genetic alterations in CT tumors concluded that CT is not due to SDH-inactivating or KIT- andPDGFRA-activating mutations.

Aberrant DNA hypermethylation of SDHC: a novel mechanism of tumor development in Carney triad.

Analysis of DNA methylation patterns in CpG islands in proximity to the gene loci of all four SDH subunits suggests epigenetic inactivation of the SDHC gene locus with functional impairment of theSDH complex as a plausible alternate mechanism of tumorigenesis in CT.

Counseling patients with succinate dehydrogenase subunit defects: genetics, preventive guidelines, and dealing with uncertainty

This work presents the approach for counseling these families at risk for developing malignancies in the context of the current uncertainties, while striving to maintain patient autonomy.

Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations

WT GISTs, particularly those in younger patients, have defects in SDH mitochondrial complex II, and in a subset of these patients, GIST seems to arise from germline-inactivating SDH mutations.

Familial paraganglioma and gastric stromal sarcoma: a new syndrome distinct from the Carney triad.

It is suggested that a new syndrome exists with paraganglioma and gastric stromal sarcoma, a condition that is familial and distinct from the Carney triad.

Pituitary adenoma with paraganglioma/pheochromocytoma (3PAs) and succinate dehydrogenase defects in humans and mice.

Using Sdhb(+/-) mice, it is provided evidence that pituitary hyperplasia in SDHx-deficient cells may be the initial abnormality in the cascade of events leading to PA formation, and the existence of a new association that is termed 3PAs is confirmed.

Carney triad: a syndrome featuring paraganglionic, adrenocortical, and possibly other endocrine tumors.

  • J. Carney
  • Medicine
    The Journal of clinical endocrinology and metabolism
  • 2009
The Carney triad is a chronic, persistent, indolent but sometimes fatal disorder of unknown etiology.

SDHB immunohistochemistry: a useful tool in the diagnosis of Carney–Stratakis and Carney triad gastrointestinal stromal tumors

It is shown that Carney–Stratakis syndrome- and Carney-triad-associated GISTs are negative by immunohistochemistry for SDHB in contrast to KIT- or PDGFRA-mutated GIST’s and a majority of sporadic Gists.