Carney–Stratakis Syndrome (CSS) — Disease Characteristics Research Report

1. Disease information

Overview / definition

Carney–Stratakis syndrome (CSS) is a rare hereditary tumor-predisposition syndrome defined by the dyad of paraganglioma (PGL) and/or pheochromocytoma (PCC) together with gastrointestinal stromal tumor (GIST), typically a KIT/PDGFRA-wildtype, succinate dehydrogenase (SDH)-deficient GIST. (khurana2019paragangliomasincarney–stratakis pages 1-2, pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2)

Synonyms / alternative names include “Carney–Stratakis dyad,” “dyad of paraganglioma and GIST,” and “hereditary GIST–paraganglioma syndrome.” (khurana2019paragangliomasincarney–stratakis pages 1-2, pasini2008clinicalandmolecular pages 1-2)

Evidence type: The syndrome definition and genotype–phenotype associations are derived from aggregated disease-level resources (reviews, guidelines) and from small family series/case reports due to rarity. (pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2)

Key identifiers (requested: OMIM/Orphanet/ICD/MeSH/MONDO)

Using the available tools in this run, I was not able to directly retrieve authoritative database identifiers (OMIM, Orphanet, MeSH, ICD-10/11, MONDO) for CSS; therefore these identifiers are not reported here to avoid uncited or incorrect mapping.

2. Etiology

Primary causes

Genetic (germline) SDH complex loss-of-function is the established cause of classic CSS. Multiple sources describe CSS as autosomal dominant with incomplete penetrance and as being caused by germline heterozygous loss-of-function pathogenic variants in SDH subunit genes, especially SDHB, SDHC, SDHD. (pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2, pasini2008clinicalandmolecular pages 4-6)

Abstract-supported definition (example quote): Lobato et al. state, “Carney-Stratakis syndrome (CSS) is an autosomal dominant rare syndrome, with incomplete penetrance, characterized by the association of paragangliomas and/or pheochromocytomas and gastrointestinal stromal tumors (GISTs).” (lobato2023threecasesof pages 1-2)

Risk factors

• Family history / inherited SDHx pathogenic variants are the main risk factors; CSS cases can still occur with limited family history due to incomplete penetrance and variable expressivity. (khurana2019paragangliomasincarney–stratakis pages 1-2, pasini2008clinicalandmolecular pages 4-6)
• Parent-of-origin effects are noted in SDH-related paraganglioma syndromes (especially SDHD) and can obscure family history patterns (more prominent in the broader SDH-PGL literature than in CSS-specific cohorts). (pitsava2021carneytriadcarneystratakis pages 3-4)

Protective factors / gene–environment interactions

No protective factors or gene–environment interactions specific to CSS were identified in the retrieved sources.

3. Phenotypes (clinical spectrum)

Core phenotypes

CSS manifests as combinations of: 1) Paragangliomas (PGLs) and/or pheochromocytomas (PCCs), often multicentric/multifocal. (khurana2019paragangliomasincarney–stratakis pages 1-2, pasini2008clinicalandmolecular pages 1-2) 2) Gastrointestinal stromal tumors (GISTs) that are SDH-deficient and usually KIT/PDGFRA-wildtype; in CSS, GISTs are frequently multifocal and preferentially gastric. (khurana2019paragangliomasincarney–stratakis pages 3-4, pasini2008clinicalandmolecular pages 1-2, khurana2019paragangliomasincarney–stratakis pages 2-3)

Khurana et al. emphasize that CSS has “greater relative frequency of PGL over GISTs,” and that “PGLs in CSS are multicentric and GISTs are multifocal.” (khurana2019paragangliomasincarney–stratakis pages 1-2)

Phenotype characteristics

• Age of onset: CSS and SDH-deficient GISTs are enriched in younger patients; in the landmark CSS genetic series, affected individuals were young (e.g., earlier series average age reported as ~23 years). (pasini2008clinicalandmolecular pages 1-2)
• GIST anatomy and pathology: SDH-deficient GISTs are described as predominantly gastric, often epithelioid or mixed morphology, multinodular/plexiform growth, multiple tumors, lymphovascular invasion, and occasional lymph node metastasis. (khurana2019paragangliomasincarney–stratakis pages 3-4, kim2024pathologicdiagnosisand pages 3-4, kim2024pathologicdiagnosisand pages 1-3)
• PGL/PCC: PGLs are neuroendocrine tumors of neural crest origin and are commonly in head/neck or retroperitoneal regions; CSS can present with unusual locations (e.g., bladder PGL described in a CSS case report). (shi2022bladderparagangliomagastrointestinal pages 1-2)

Suggested HPO terms (non-exhaustive)

• Paraganglioma: HP:0002666
• Pheochromocytoma: HP:0002667
• Gastrointestinal stromal tumor: HP:0031275 (term name varies by HPO version; use nearest GIST term)
• Gastrointestinal hemorrhage (if present): HP:0002239
• Abdominal pain: HP:0002027
• Gastrointestinal neoplasm (broad): HP:0007378

Note: Exact HPO IDs for “GIST” should be verified against the current HPO release when implementing.

4. Genetic / molecular information

Causal genes (CSS)

Classic CSS is most consistently linked to germline loss-of-function variants in: - SDHB (HGNC:10681) - SDHC (HGNC:10682) - SDHD (HGNC:10683)

These genes encode subunits of mitochondrial complex II (SDH), and germline disruption predisposes to the CSS dyad. (pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2, pasini2008clinicalandmolecular pages 4-6)

SDHA is frequently mutated in SDH-deficient GIST overall, but recent review synthesis indicates SDHA germline cases more often present as isolated SDH-deficient GIST rather than classic CSS; co-occurrence with PGL is described as rare. (schipani2023sdhagermlinemutations pages 8-9)

Pathogenic variants (representative examples)

In the landmark CSS series, Pasini et al. studied 11 patients and reported that in eight (from seven unrelated families) GISTs were caused by germline mutations in SDHB, SDHC, or SDHD, with autosomal-dominant inheritance and incomplete penetrance. (pasini2008clinicalandmolecular pages 1-2)

Reported variants from the Pasini cohort include (examples; not exhaustive): - SDHB: c.72+1G>T, c.423+1G>C, c.45_46insCC, large deletions. (pasini2008clinicalandmolecular pages 4-6, pasini2008clinicalandmolecular pages 1-2) - SDHC: c.43C>T (p.Arg15X), c.405+1G>A (splice), and later a germline SDHC exon 3 deletion reported in a 2023 case series. (pasini2008clinicalandmolecular pages 4-6, lobato2023threecasesof pages 1-2) - SDHD: c.57delG. (pasini2008clinicalandmolecular pages 1-2)

Inheritance pattern and penetrance

CSS is described as autosomal dominant with incomplete penetrance, supported by unaffected mutation carriers in pedigrees (e.g., SDHB/SDHC splice variants inherited from clinically unaffected mothers). (pasini2008clinicalandmolecular pages 4-6, pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2)

Quantitative penetrance estimates are more available for SDHx carrier cohorts broadly (PPGL predisposition) than for CSS specifically. For example, SDH-related syndromes have subunit-specific penetrance features; one synthesis notes SDHB has lower penetrance but higher metastatic risk, while SDHD often has higher penetrance and head/neck predominance. (pitsava2021carneytriadcarneystratakis pages 3-4)

Variant type and mechanism

Most CSS variants are consistent with loss of function (splice-site, nonsense, frameshift, or large deletion), consistent with tumor-suppressor biology and frequent “second-hit” loss of the wild-type allele (LOH) in tumors. (pasini2008clinicalandmolecular pages 4-6)

5. Environmental information

No consistent non-genetic environmental triggers, lifestyle determinants, or infectious agents specific to CSS were identified in the retrieved literature. CSS is primarily genetic. (pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2)

6. Mechanism / pathophysiology

Core causal chain (from germline SDHx loss to tumors)

1) Germline SDHx loss-of-function → reduced SDH (mitochondrial complex II) activity in susceptible tissues. (pasini2008clinicalandmolecular pages 1-2, khurana2019paragangliomasincarney–stratakis pages 2-3) 2) Succinate accumulation (oncometabolite) due to impaired conversion of succinate to fumarate. (pitsava2021carneytriadcarneystratakis pages 3-4, khurana2019paragangliomasincarney–stratakis pages 2-3) 3) Pseudohypoxia: succinate inhibits prolyl hydroxylases, stabilizing HIF-1α, driving hypoxia-like transcriptional programs. (khurana2019paragangliomasincarney–stratakis pages 2-3) 4) Epigenetic reprogramming: succinate inhibits TET/JmjC demethylases, promoting DNA/histone hypermethylation and altered differentiation programs. (pitsava2021carneytriadcarneystratakis pages 3-4, khurana2019paragangliomasincarney–stratakis pages 2-3) 5) Downstream signaling changes in SDH-deficient GIST can include VEGF/IGF2 upregulation and activation of PI3K/AKT and MAPK signaling as summarized in a 2024 mini-review. (kim2024pathologicdiagnosisand pages 3-4)

GO and CL term suggestions (mechanism anchoring)

• GO:0006121 mitochondrial electron transport, succinate to ubiquinone
• GO:0006099 tricarboxylic acid cycle
• GO:0001666 response to hypoxia
• GO:0071559 response to hypoxia-inducible factor (or related HIF terms depending on GO version)
• GO:0006325 chromatin organization; GO:0043044 ATP-dependent chromatin remodeling (as downstream)
• CL (cell types relevant to lesions):
• Chromaffin cell (adrenal medulla) / paraganglionic cells (CL term mapping should be validated)
• Interstitial cells of Cajal (cell-of-origin for GIST; CL mapping requires validation)

7. Anatomical structures affected

Primary organs / structures

• Stomach (predominant site for SDH-deficient GIST). (khurana2019paragangliomasincarney–stratakis pages 3-4, kim2024pathologicdiagnosisand pages 1-3)
• Paraganglia along the paravertebral axis; adrenal medulla for PCC. (khurana2019paragangliomasincarney–stratakis pages 1-2, khurana2019paragangliomasincarney–stratakis pages 2-3)

UBERON term suggestions

• Stomach: UBERON:0000945
• Adrenal gland: UBERON:0002369 (adrenal medulla is a substructure)
• Paraganglion: UBERON mapping should be validated for “paraganglion” specific class

Subcellular localization

SDH is localized to the mitochondrial inner membrane (complex II); dysfunction is therefore a mitochondrial metabolic defect. (khurana2019paragangliomasincarney–stratakis pages 2-3)

8. Temporal development

Onset and course

CSS often presents in childhood/adolescence/young adulthood, particularly for SDH-deficient GIST, and can show multifocal tumors and metastatic potential but with variable/indolent clinical courses in some cases. (khurana2019paragangliomasincarney–stratakis pages 3-4, pasini2008clinicalandmolecular pages 1-2)

9. Inheritance and population

Epidemiology

CSS is rare; no robust prevalence/incidence estimates were retrieved in the available texts for this run.

Sex ratio

Reviews describe CSS as affecting both genders (in contrast to Carney triad, which has female predilection). (pitsava2021carneytriadcarneystratakis pages 3-4)

Tumor risk statistics (from SDHB carrier surveillance cohorts; not CSS-specific)

A surveillance series summarized in a 2019 SDH-deficient GIST management review reported that among 65 asymptomatic SDHB mutation carriers undergoing annual abdominal MRI-based surveillance, 25% developed SDHB-related cancers within 6 years, and 16.6% had an asymptomatic tumor detected on the first surveillance scan. (neppala2019currentmanagementof pages 6-7)

10. Diagnostics

Pathology and immunohistochemistry

Loss of SDHB immunohistochemical staining is a validated surrogate marker of SDH deficiency and helps distinguish SDH-deficient GIST (including CSS-associated tumors) from KIT/PDGFRA-mutant GIST. (gaal2011sdhbimmunohistochemistrya pages 6-8)

A representative example of this real-world diagnostic pattern is shown in Gaal et al. Figure 1 panel (a): a CSS-associated GIST demonstrates negative SDHB staining in tumor cells, with endothelial cells serving as internal positive control. (gaal2011sdhbimmunohistochemistrya media 9958076a)

Molecular testing

• CSS workup commonly includes tumor and germline testing of SDHx genes by NGS, with copy-number analysis (e.g., MLPA) when sequencing is negative but suspicion remains. A 2023 case series illustrates that NGS/MLPA may be negative in clinically consistent CSS, highlighting genetic heterogeneity and potential underdiagnosis; they also report an SDHC exon 3 deletion not previously reported. (lobato2023threecasesof pages 1-2)
• In CSS-associated tumors, GISTs typically lack common KIT/PDGFRA driver mutations. (pasini2008clinicalandmolecular pages 1-2)

Biochemical testing (PPGL)

Biochemical evaluation for catecholamine excess (e.g., plasma metanephrines/normetanephrines) is used in real-world CSS/PCC evaluation and perioperative planning (α-blockade). (lobato2023threecasesof pages 1-2)

Imaging

Cross-sectional imaging (CT/MRI) and functional imaging (e.g., PET/CT) are used for tumor localization and staging in CSS cases and broader SDHx syndromes. (lobato2023threecasesof pages 1-2, khurana2019paragangliomasincarney–stratakis pages 2-3)

Differential diagnosis

Key distinctions include: - Carney triad (PGL + GIST + pulmonary chondroma), often associated with SDHC promoter hypermethylation and female predominance, and frequently non-hereditary/mosaic rather than classic autosomal dominant inheritance. (pitsava2021carneytriadcarneystratakis pages 3-4) - Sporadic KIT/PDGFRA-mutant GIST (typically SDHB-positive by IHC). (gaal2011sdhbimmunohistochemistrya pages 6-8)

11. Outcome / prognosis

No CSS-specific survival rates were identified in retrieved sources. SDH-deficient GIST can metastasize (including nodal metastasis) yet may have relatively indolent behavior compared with other GIST subsets, with clinical course varying substantially. (khurana2019paragangliomasincarney–stratakis pages 3-4, kim2024pathologicdiagnosisand pages 3-4)

12. Treatment

Surgical management (current standard)

For localized CSS-associated tumors, complete surgical resection is a primary approach, particularly because SDH-deficient GIST is often not responsive to standard KIT-directed tyrosine kinase inhibitors. (shi2022bladderparagangliomagastrointestinal pages 1-2, neppala2019currentmanagementof pages 1-2)

Systemic therapy considerations

• Imatinib: SDH-deficient GISTs are generally described as poorly responsive, which is clinically important in CSS because these tumors are frequently KIT/PDGFRA-wildtype. (khurana2019paragangliomasincarney–stratakis pages 4-4, neppala2019currentmanagementof pages 1-2)
• Anti-angiogenic TKIs (e.g., sunitinib, regorafenib, pazopanib) and other systemic options are discussed in reviews for SDH-deficient tumors, but evidence remains limited and often extrapolated from broader SDH-deficient GIST/PPGL experiences. (khurana2019paragangliomasincarney–stratakis pages 3-4, schipani2023sdhagermlinemutations pages 8-9)

Surveillance / follow-up (real-world implementation)

For completely resected SDH-deficient GIST, a commonly cited follow-up framework includes physical exams and cross-sectional abdominal/pelvic imaging every 3–6 months for 5 years, then annually, as summarized in a management review discussing guideline-consistent practices. (neppala2019currentmanagementof pages 6-7)

Relevant clinical trials

• Guadecitabine (SGI-110) DNMT inhibitor for SDH-deficient tumors: Phase II trial NCT03165721 (ClinicalTrials.gov; first posted 2017; start date 2017-08-16; primary completion 2020-02-24) evaluated guadecitabine in wt/SDH-deficient GIST and SDH-mutant PPGL strata; the study was terminated due to low accrual. URL: https://clinicaltrials.gov/study/NCT03165721 (NCT03165721 chunk 1, NCT03165721 chunk 2)
• Natural history / biospecimen study: NCT03739827 (recruiting; sponsor NCI; primary completion 2028-05-31) includes “SDH deficient GIST” and “Paraganglioma,” enrolling germline variant carriers and relatives to collect biospecimens, imaging, and longitudinal clinical data. URL: https://clinicaltrials.gov/study/NCT03739827 (NCT03739827 chunk 1)

Suggested MAXO terms

• Surgical resection: MAXO:0000011 (surgery; verify exact child term)
• Genetic counseling: MAXO:0000075 (verify)
• Tumor surveillance / screening: MAXO:0000127 (verify)
• α-adrenergic blockade for PCC: MAXO mapping should be validated

13. Prevention

Primary prevention is not established for CSS because it is an inherited tumor predisposition syndrome. Secondary/tertiary prevention relies on genetic counseling, cascade testing, and surveillance imaging/biochemical monitoring for early tumor detection and management in SDHx variant carriers. (neppala2019currentmanagementof pages 6-7, lobato2023threecasesof pages 1-2)

14. Other species / natural disease

No naturally occurring CSS analog in non-human species was identified in retrieved sources.

15. Model organisms

The retrieved sources for this run did not provide explicit descriptions of CSS-specific model organisms (e.g., SDHx mouse models reproducing the dyad phenotype). Mechanistic descriptions strongly implicate mitochondrial metabolism and epigenetic dysregulation in SDH-deficient tumors, but dedicated model-system evidence should be curated from additional experimental literature beyond the documents retrieved here. (pitsava2021carneytriadcarneystratakis pages 3-4, khurana2019paragangliomasincarney–stratakis pages 2-3)

High-level synthesis (2023–2024 emphasis)

Recent case-based and pathology-focused literature reinforces that CSS should be considered when encountering SDH-deficient, KIT/PDGFRA-wildtype gastric GIST and/or PGL/PCC, and that SDHx testing should include deletion/duplication analysis when sequencing is negative. (lobato2023threecasesof pages 1-2, kim2024pathologicdiagnosisand pages 3-4)

A 2024 mini-review summarizes modern diagnostic practice for molecularly diverse GIST, emphasizing that ancillary testing (IHC, NGS) is essential because some epithelioid/mixed tumors may lose canonical KIT/DOG1 signals, and that SDH-deficient GIST (including CSS-associated) behaves as a distinct subgroup with TKI resistance. (kim2024pathologicdiagnosisand pages 3-4)

Summary table

Table: This table condenses the key definitional, genetic, mechanistic, and diagnostic facts about Carney–Stratakis syndrome for rapid knowledge-base entry. It highlights the SDHx basis of the syndrome, classic tumor dyad, hallmark pathology, and the most relevant 2023–2024 sources.

Key visual evidence

• SDHB-negative immunohistochemistry pattern in CSS-associated GIST (diagnostic hallmark): (gaal2011sdhbimmunohistochemistrya media 9958076a)

References

1. (khurana2019paragangliomasincarney–stratakis pages 1-2): Arushi Khurana, Lin Mei, Anthony C. Faber, Steven C. Smith, and Sosipatros A. Boikos. Paragangliomas in carney–stratakis syndrome. Hormone and Metabolic Research, 51:437-442, Jun 2019. URL: https://doi.org/10.1055/a-0918-8340, doi:10.1055/a-0918-8340. This article has 6 citations and is from a peer-reviewed journal.

2. (pasini2008clinicalandmolecular pages 1-2): Barbara Pasini, Sarah R McWhinney, Thalia Bei, Ludmila Matyakhina, Sotirios Stergiopoulos, Michael Muchow, Sosipatros A Boikos, Barbara Ferrando, Karel Pacak, Guillaume Assie, Eric Baudin, Agnes Chompret, Jay W Ellison, Jean-Jacques Briere, Pierre Rustin, Anne-Paule Gimenez-Roqueplo, Charis Eng, J Aidan Carney, and Constantine A Stratakis. Clinical and molecular genetics of patients with the carney–stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits sdhb, sdhc, and sdhd. European Journal of Human Genetics, 16:79-88, Aug 2008. URL: https://doi.org/10.1038/sj.ejhg.5201904, doi:10.1038/sj.ejhg.5201904. This article has 581 citations and is from a domain leading peer-reviewed journal.

3. (lobato2023threecasesof pages 1-2): Eduardo C Lobato, Felipe F Castro, Lucas S Santana, Ibere C Soares, Gustavo F C Fagundes, and Madson Q Almeida. Three cases of carney-stratakis syndrome: a genetically heterogeneous disease. JCEM Case Reports, Nov 2023. URL: https://doi.org/10.1210/jcemcr/luad139, doi:10.1210/jcemcr/luad139. This article has 2 citations.

4. (pasini2008clinicalandmolecular pages 4-6): Barbara Pasini, Sarah R McWhinney, Thalia Bei, Ludmila Matyakhina, Sotirios Stergiopoulos, Michael Muchow, Sosipatros A Boikos, Barbara Ferrando, Karel Pacak, Guillaume Assie, Eric Baudin, Agnes Chompret, Jay W Ellison, Jean-Jacques Briere, Pierre Rustin, Anne-Paule Gimenez-Roqueplo, Charis Eng, J Aidan Carney, and Constantine A Stratakis. Clinical and molecular genetics of patients with the carney–stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits sdhb, sdhc, and sdhd. European Journal of Human Genetics, 16:79-88, Aug 2008. URL: https://doi.org/10.1038/sj.ejhg.5201904, doi:10.1038/sj.ejhg.5201904. This article has 581 citations and is from a domain leading peer-reviewed journal.

5. (pitsava2021carneytriadcarneystratakis pages 3-4): Georgia Pitsava, Nikolaos Settas, Fabio R. Faucz, and Constantine A. Stratakis. Carney triad, carney-stratakis syndrome, 3pas and other tumors due to sdh deficiency. Frontiers in Endocrinology, May 2021. URL: https://doi.org/10.3389/fendo.2021.680609, doi:10.3389/fendo.2021.680609. This article has 54 citations.

6. (khurana2019paragangliomasincarney–stratakis pages 3-4): Arushi Khurana, Lin Mei, Anthony C. Faber, Steven C. Smith, and Sosipatros A. Boikos. Paragangliomas in carney–stratakis syndrome. Hormone and Metabolic Research, 51:437-442, Jun 2019. URL: https://doi.org/10.1055/a-0918-8340, doi:10.1055/a-0918-8340. This article has 6 citations and is from a peer-reviewed journal.

7. (khurana2019paragangliomasincarney–stratakis pages 2-3): Arushi Khurana, Lin Mei, Anthony C. Faber, Steven C. Smith, and Sosipatros A. Boikos. Paragangliomas in carney–stratakis syndrome. Hormone and Metabolic Research, 51:437-442, Jun 2019. URL: https://doi.org/10.1055/a-0918-8340, doi:10.1055/a-0918-8340. This article has 6 citations and is from a peer-reviewed journal.

8. (kim2024pathologicdiagnosisand pages 3-4): Younghoon Kim and Sung Hak Lee. Pathologic diagnosis and molecular features of gastrointestinal stromal tumors: a mini-review. Frontiers in Oncology, Nov 2024. URL: https://doi.org/10.3389/fonc.2024.1487467, doi:10.3389/fonc.2024.1487467. This article has 10 citations.

9. (kim2024pathologicdiagnosisand pages 1-3): Younghoon Kim and Sung Hak Lee. Pathologic diagnosis and molecular features of gastrointestinal stromal tumors: a mini-review. Frontiers in Oncology, Nov 2024. URL: https://doi.org/10.3389/fonc.2024.1487467, doi:10.3389/fonc.2024.1487467. This article has 10 citations.

10. (shi2022bladderparagangliomagastrointestinal pages 1-2): Yihang Shi, Li Ding, Chengqiang Mo, Yanji Luo, Shaoqing Huang, Shirong Cai, Yanzhe Xia, and Xinhua Zhang. Bladder paraganglioma, gastrointestinal stromal tumor, and sdhb germline mutation in a patient with carney-stratakis syndrome: a case report and literature review. Frontiers in Oncology, Oct 2022. URL: https://doi.org/10.3389/fonc.2022.1030092, doi:10.3389/fonc.2022.1030092. This article has 6 citations.

11. (schipani2023sdhagermlinemutations pages 8-9): Angela Schipani, Margherita Nannini, Annalisa Astolfi, and Maria A. Pantaleo. Sdha germline mutations in sdh-deficient gists: a current update. Genes, 14:646, Mar 2023. URL: https://doi.org/10.3390/genes14030646, doi:10.3390/genes14030646. This article has 24 citations.

12. (neppala2019currentmanagementof pages 6-7): Pushpa Neppala, Sudeep Banerjee, Paul T. Fanta, Mayra Yerba, Kevin A. Porras, Adam M. Burgoyne, and Jason K. Sicklick. Current management of succinate dehydrogenase–deficient gastrointestinal stromal tumors. Cancer and Metastasis Reviews, 38:525-535, Sep 2019. URL: https://doi.org/10.1007/s10555-019-09818-0, doi:10.1007/s10555-019-09818-0. This article has 62 citations and is from a peer-reviewed journal.

13. (gaal2011sdhbimmunohistochemistrya pages 6-8): José Gaal, Constantine A Stratakis, J Aidan Carney, Evan R Ball, Esther Korpershoek, Maya B Lodish, Isaac Levy, Paraskevi Xekouki, Francien H van Nederveen, Michael A den Bakker, Maureen O'Sullivan, Winand NM Dinjens, and Ronald R de Krijger. Sdhb immunohistochemistry: a useful tool in the diagnosis of carney–stratakis and carney triad gastrointestinal stromal tumors. Modern Pathology, 24:147-151, Jan 2011. URL: https://doi.org/10.1038/modpathol.2010.185, doi:10.1038/modpathol.2010.185. This article has 252 citations and is from a domain leading peer-reviewed journal.

14. (gaal2011sdhbimmunohistochemistrya media 9958076a): José Gaal, Constantine A Stratakis, J Aidan Carney, Evan R Ball, Esther Korpershoek, Maya B Lodish, Isaac Levy, Paraskevi Xekouki, Francien H van Nederveen, Michael A den Bakker, Maureen O'Sullivan, Winand NM Dinjens, and Ronald R de Krijger. Sdhb immunohistochemistry: a useful tool in the diagnosis of carney–stratakis and carney triad gastrointestinal stromal tumors. Modern Pathology, 24:147-151, Jan 2011. URL: https://doi.org/10.1038/modpathol.2010.185, doi:10.1038/modpathol.2010.185. This article has 252 citations and is from a domain leading peer-reviewed journal.

15. (neppala2019currentmanagementof pages 1-2): Pushpa Neppala, Sudeep Banerjee, Paul T. Fanta, Mayra Yerba, Kevin A. Porras, Adam M. Burgoyne, and Jason K. Sicklick. Current management of succinate dehydrogenase–deficient gastrointestinal stromal tumors. Cancer and Metastasis Reviews, 38:525-535, Sep 2019. URL: https://doi.org/10.1007/s10555-019-09818-0, doi:10.1007/s10555-019-09818-0. This article has 62 citations and is from a peer-reviewed journal.

16. (khurana2019paragangliomasincarney–stratakis pages 4-4): Arushi Khurana, Lin Mei, Anthony C. Faber, Steven C. Smith, and Sosipatros A. Boikos. Paragangliomas in carney–stratakis syndrome. Hormone and Metabolic Research, 51:437-442, Jun 2019. URL: https://doi.org/10.1055/a-0918-8340, doi:10.1055/a-0918-8340. This article has 6 citations and is from a peer-reviewed journal.

17. (NCT03165721 chunk 1): John Glod. A Phase II Trial of the DNA Methyl Transferase Inhibitor, Guadecitabine (SGI-110), in Children and Adults With Wild Type GIST,Pheochromocytoma and Paraganglioma Associated With Succinate Dehydrogenase Deficiency and HLRCC-associated Kidney Cancer. National Cancer Institute (NCI). 2017. ClinicalTrials.gov Identifier: NCT03165721

18. (NCT03165721 chunk 2): John Glod. A Phase II Trial of the DNA Methyl Transferase Inhibitor, Guadecitabine (SGI-110), in Children and Adults With Wild Type GIST,Pheochromocytoma and Paraganglioma Associated With Succinate Dehydrogenase Deficiency and HLRCC-associated Kidney Cancer. National Cancer Institute (NCI). 2017. ClinicalTrials.gov Identifier: NCT03165721

19. (NCT03739827 chunk 1): Natural History and Biospecimen Acquisition for Children and Adults With Rare Solid Tumors. National Cancer Institute (NCI). 2019. ClinicalTrials.gov Identifier: NCT03739827

20. (schipani2023sdhagermlinemutations pages 1-2): Angela Schipani, Margherita Nannini, Annalisa Astolfi, and Maria A. Pantaleo. Sdha germline mutations in sdh-deficient gists: a current update. Genes, 14:646, Mar 2023. URL: https://doi.org/10.3390/genes14030646, doi:10.3390/genes14030646. This article has 24 citations.

21. (florou2025areviewof pages 4-4): Vaia Florou, Michelle F. Jacobs, Ruth Casey, Denisse Evans, Becky Owens, Margarita Raygada, Sara Rothschild, and Samantha E. Greenberg. A review of genomic testing and sdh‐ deficiency in gastrointestinal stromal tumors: getting to the gist. Cancer Medicine, Feb 2025. URL: https://doi.org/10.1002/cam4.70669, doi:10.1002/cam4.70669. This article has 8 citations and is from a peer-reviewed journal.