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HelpTest ID: HPGLP Hereditary Paraganglioma/Pheochromocytoma Panel, Varies
Ordering Guidance
Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.
Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. For more information see FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated
Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. Molecular Genetics: Inherited Cancer Syndromes Patient Information Sheet (T519)
3. If not ordering electronically, complete, print, and send a Oncology Test Request (T729) with the specimen.
Useful For
Evaluating patients with a personal or family history suggestive of a hereditary paraganglioma and pheochromocytoma (PGL/PCC) syndrome
Establishing a diagnosis of a hereditary PGL/PCC, allowing for targeted surveillance based on associated risks
Identifying genetic variants associated with increased risk for PGL/PCC, allowing for predictive testing and appropriate screening of at-risk family members
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 11 genes associated with hereditary paraganglioma and/or pheochromocytoma (PGL/PCC): FH, MAX, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, and VHL. For more information see Method Description and Targeted Genes and Methodology Details for Hereditary Paraganglioma/Pheochromocytoma Panel.
Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for hereditary PGL/PCC.
Method Name
Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.
Reporting Name
Hereditary PGL/PCC PanelSpecimen Type
VariesSpecimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Clinical Information
Paragangliomas (PGL)and pheochromocytomas (PCC) are rare neuroendocrine tumors that arise from autonomous ganglia. Tumors located within the adrenal medulla (the largest sympathetic ganglion) are called pheochromocytomas, while those that stem from either parasympathetic or sympathetic ganglia are designated paragangliomas.
PGL/PCC have a germline genetic basis in up to 30% of cases.(1) The genes implicated in hereditary PGL/PCC syndrome include MAX, TMEM127, FH, and the SDHx genes.
The genes most frequently associated with hereditary PGL/PCC syndromes are the succinate dehydrogenase-associated genes SDHA, SDHAF2, SDHB, SDHC, and SDHD.
Germline alterations in the MAX gene are typically associated with increased risk for PCC, although some individuals have been identified with PGL. MAX variants occur in approximately 1% of patients with hereditary PGL/PCC syndromes.(2)
TMEM127 variants are associated most commonly with PCC and rarely PGL.(1) Alterations of TMEM127 account for approximately 2% of individuals with hereditary PGL/PCC.(2)
Recent evidence suggests that disease-causing variants in FH also increase risk for PGL/PCC.(3,4) Individuals with disease-causing FH variants carry a significantly increased risk for cutaneous or uterine leiomyomata and renal tumors.(5)
Alterations in VHL, NF1, and RET also increase risk for PGL/PCC, in addition to other types of tumors.(6)
Disease-causing variants in the VHL gene are associated with a syndrome called von Hippel Lindau (VHL) syndrome. In addition to PGL/PCC, individuals with VHL syndrome are at increased risk for hemangioblastomas, renal cell carcinoma, pancreatic cysts, neuroendocrine tumors, endolymphatic sac and epididymal tumors.(7)
NF1 gene variants are associated with neurofibromatosis type I (NF1). Individuals with NF1 are at increased risk for pheochromocytomas in addition to neurofibromas and central nervous system gliomas, such as optic nerve gliomas. NF1 is also characterized by other features such as cafe-au lait macules, axillary/inguinal freckling and Lisch nodules.(8)
Disease-causing RET variants result in a syndrome called multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid cancer (FMTC). In addition to an increased risk for PGL/PCC, individuals with MEN2/FMTC have a very high risk of developing medullary thyroid cancer. Individuals with MEN2 may also have other features, such as primary hyperparathyroidism, mucosal neuromas, ganglioneuromatosis, and distinctive facial features.(9)
The National Comprehensive Cancer Network and the American Cancer Society provide recommendations regarding the medical management of individuals with hereditary PGL/PCC syndromes.(10)
Reference Values
An interpretive report will be provided.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(11) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Clinical Reference
1. Else T, Greenberg S, Fishbein L: In: Adam MP, Everman DB, Mirzaa GM, et al, eds. Hereditary paraganglioma-pheochromocytoma syndromes. GeneReviews [Internet]. University of Washington, Seattle; 2008. Updated September 21, 2023. Accessed April 25,2024. Available at www.ncbi.nlm.nih.gov/books/NBK1548/
2. Bausch B, Schiavi F, Ni Y, et al. European-American-Asian Pheochromocytoma-Paraganglioma Registry Study Group. Clinical characterization of the pheochromocytoma and paraganglioma susceptibility genes SDHA, TMEM127, MAX, and SDHAF2 for gene-informed prevention. JAMA Oncol. 2017;3(9):1204-1212
3. Udager AM, Magers MJ, Goerke DM, et al. The utility of SDHB and FH immunohistochemistry in patients evaluated for hereditary paraganglioma-pheochromocytoma syndromes. Hum Pathol. 2018;71:47-54
4. Castro-Vega LJ, Buffet A, De Cubas AA, et al. Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas. Hum Mol Genet. 2014;23(9):2440-2446. doi: 10.1093/hmg/ddt639
5. Kamihara J, Schultz KA, Rana HQ. FH tumor predisposition syndrome. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2006. Updated August 13, 2020. Accessed April 25, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1252/
6. Shah MH, Goldner WS, Halfdanarson TR et al. NCCN Guidelines Insights: Neuroendocrine and Adrenal Tumors, Version 2.2018. J Natl Compr Canc Netw. 2018;16(6):693-702
7. van Leeuwaarde RS, Ahmad S, Links TP, et al: Von Hippel-Lindau syndrome. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated February 29, 2024. Accessed April 25, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1463/
8. Friedman JM: Neurofibromatosis 1. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1998. Updated April 21, 2022. Accessed April 25, 2025. Available at www.ncbi.nlm.nih.gov/books/NBK1109/
9. Eng C: Multiple Endocrine Neoplasia Type 2. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1999. Updated August 10, 2023. Accessed April 25, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1257/
10. Benn DE, Gimenez-Roqueplo AP, Reilly JR, et al. Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J Clin Endocrinol Metab. 2006;91(3):827-836
11. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424
Day(s) Performed
Varies
Report Available
14 to 21 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81437
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| HPGLP | Hereditary PGL/PCC Panel | In Process |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 614731 | Test Description | 62364-5 |
| 614732 | Specimen | 31208-2 |
| 614733 | Source | 31208-2 |
| 614734 | Result Summary | 50397-9 |
| 614735 | Result | 82939-0 |
| 614736 | Interpretation | 69047-9 |
| 614737 | Resources | 99622-3 |
| 614738 | Additional Information | 48767-8 |
| 614739 | Method | 85069-3 |
| 614740 | Genes Analyzed | 48018-6 |
| 614741 | Disclaimer | 62364-5 |
| 614742 | Released By | 18771-6 |
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