Preferred initial test when hereditary paraganglioma-pheochromocytoma is suspected.
- Patient Preparation
- Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 2 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
Characteristics: Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are characterized by paragangliomas (neuroendocrine tumors of the autonomic nervous system) and pheochromocytomas (paragangliomas of the adrenal medulla). Pathogenic germline mutations in a number of genes, including SDHB, SDHC, and SDHD, predispose to paraganglioma and pheochromocytoma with risk of malignant transformation.
Incidence: About 1 in 300,000 per year.
Inheritance: Autosomal dominant; parent of origin effect for SDHD.
Cause: Pathogenic succinate dehydrogenase, subunits B, C, and D (SDHB, SDHC, and SDHD) gene mutations. Mutations in other genes, including TMEM127, EGLN1, MAX, SDHA, and SDHAF2, may also be causative.
Clinical Sensitivity: 26-30 percent.
Methodology: Bidirectional sequencing of all coding regions and intron-exon boundaries of the SDHB, SDHC, and SDHD genes; Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large SDHB, SDHC, and SDHD deletions/duplications.
Analytical Sensitivity and Specificity: Sequencing: 99 percent; MLPA: 90 and 99 percent, respectively.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations and deep intronic mutations will not be detected. The breakpoints of large deletions/duplications will not be determined. Mutations in genes other than SDHB, SDHC, and SDHD are not evaluated. This assay is not designed to detect somatic variants associated with malignancy. Interpretation of this test result may be impacted if the patient has had an allogeneic stem cell transplantation.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|2007168||HPGL-PCC (SDHB,C,D) Seq, DelDup Specimen||31208-2|
|2007169||HPGL-PCC (SDHB,C,D) Seq, DelDup Interp||41103-3|
- Hereditary Paraganglioma-Pheochromocytoma molecular assay
- Paraganglioma (SDHB, SDHC, and SDHD) Sequencing and Deletion/Duplication
- PCC (SDHB, SDHC, and SDHD) Sequencing and Deletion/Duplication
- PGL (SDHB, SDHC, and SDHD) Sequencing and Deletion/Duplication
- Pheochromocytoma (SDHB, SDHC, and SDHD) Sequencing and Deletion/Duplication
- SDHB, SDHC, and SDHD Sequencing and Deletion/Duplication
- SDHB, SDHC, SDHD Genes
- Stromal Tumor (SDHB, SDHC, and SDHD) Sequencing and Deletion/Duplication
- Succinate Dehydrogenase genetic assay
- Succinate Dehydrogenase, subsets B, C, and D (SDHB, SDHC, and SDHD) Sequencing and Deletion/Duplicat