Hereditary Neuroendocrine Tumors


Hereditary Paraganglioma (PGL) is characterized by slow-growing tumors derived from paraganglia tissue in the head and neck, thorax, abdomen, and pelvis. Pheochromocytomas (PCC) are a type of paraganglioma that is confined to the adrenal gland, a small hormone producing organ located on top of each kidney.

Research has shown that mutations in several genes (SDHB, SDHC, SDHD, SDHA, SDHAF2, and MAX) encoding subunits of succinate dehydrogenase (SDH), or mitochondrial complex II, are responsible for most cases.

We provide testing for the genes that are believed to be associated with paragangliomas and pheochromocytomas. SDHA, SDHB, SDHC, SDHD, SDHAF2, MAX, TMEM127, & VHL.

Type Gene OMIM Description
PGL1 SDHD 168000 Mutations have been identified in multigenerational families with primarily head and neck parasympathetic paragangliomas. SDHD mutations predispose to the development of multifocal paragangliomas. In patients with SDHD mutations, penetrance depends on whether the individual inherited the mutation from the mother or the father. The disease is not manifested when the mutation is inherited from the mother, but is highly penetrant when inherited from the father. Chromosome locus 11q23. Mutations account for 50% of patients with PGL.
PGL2 SDHAF2 613019 Mutations in SDHAF2, chromosome locus 11q12.2, has been identified in people with hereditary paraganglioma-pheochromocytoma. People with this condition have paragangliomas, pheochromocytomas, or both. Analysis recommended if no mutations observed in SDHD, SDHC, or SDHB genes.
PGL3 SDHC 602413 Found in families with head and neck parasympathetic paragangliomas. Inheritance of mutations does not demonstrate the parent of origin effect observed in families with SDHD mutations. Benign tumors observed with mutations of SDHC. Chromosome locus 1q21.
PGL4 SDHB 115310 Associated with paragangliomas in abdomen, pelvis, thorax, head and neck tumors. Mutations put patients at risk for malignant paragangliomas, renal cell carcinoma, and papillary thyroid cancer. Mutations account for 38-40% of patients with PGL. Chromosome locus 1p35–36.
PGL5 SDHA 614165 Mutations associated with Leigh syndrome. Only 3 mutations have been identified on chromosome 3q29.
PCC susceptibility MAX 171300

The MAX gene encodes a protein that regulates cell growth and division. Mutations in this gene were identified in 8.5 percent of patients with either bilateral PCC or early age of onset of PCC. Mutations account for 1% of patients with PGL. Chromosome locus 14q23. Analysis recommended if no mutations observed in SDHD, SDHC, or SDHB genes.

Purpose: Confirm a genetic basis for cancer/Identify at-risk family members

Methodology: Next-Generation Sequencing

Test Requisition: Sequencing Requisition

Specimen Requirements: 2-5 mL Blood-Lavender Top Tube

Panel CPT Codes: 81437 Panel Price: $3500.00

Turn-around-time: 6 weeks

Shipping Information


1. Astuti D, Douglas F, Lennard TWJ, Aligianis IA, Woodward ER, Evans DG, Eng C, Latif F, Maher ER 2001 Germline SDHD mutation in familial phaeochromocytoma. Lancet 357:1181–1182

2. Neumann HP, Pawlu C, Peczkowska M, Bausch B, McWhinney SR, Muresan M, Buchta M, Franke G, Klisch J, Bley TA, Hoegerle S, Boedeker CC, Opocher G, Schipper J, Januszewicz A, Eng C, European-American Paraganglioma Study Group 2004 Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA292:943-951

3. Young AL, Baysal BE, Deb A, Young Jr WF 2002 Familial malignant catecholamine-secreting paraganglioma with prolonged survival associated with mutation in the succinate dehydrogenase B gene. J Clin Endocrinol Metab 87:4101–4105

4. Gimenez-Roqueplo AP, Favier J, Rustin P, Rieubland C, Crespin M, Nau V, Khau Van Kien P, Corvol P, Plouin PF, Jeunemaitre X, COMETE Network 2003 Mutations in SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. Cancer Res 63:5615–5621

5. Schiavi F, Boedeker CC, Bausch B, Peczkowska M, Gomez CF, et al. European-American Paraganglioma Study Group 2005 Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene. JAMA 294:2057–2063

6. Gimenez-Roqueplo AP, Lehnert H, Mannelli M, Neumann H, Opocher G, Maher ER,et al. Phaeochromocytoma, new genes and screening strategies. Clin Endocrinol (Oxf). 2006 Dec;65(6):699-705.

7. Hensen EF, Bayley J. Recent advances in the genetics of SDH-related paraganglioma and pheochromocytoma. Fam Cancer. 2011 Jun;10(2):355-63.

8. Mu, W, et al. "Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generation sequencing panel testing". J Mol Diagn. 2016. 18(6):923-932.




Contact Information
Genetics Laboratory
University of Oklahoma Health Sciences Center
1122 NE 13 Street, Suite 1400, Oklahoma City, OK 73104
Phone: (405) 271-3589 |Fax: (405) 271-7117 Email: Dr. Shibo Li

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