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Hereditary Paraganglioma-Pheochromocytoma Syndrome via the SDHD Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
10033 SDHD 81404 81404,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10033SDHD81404 81404,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Hannah Cox, PhD

Clinical Features and Genetics

Clinical Features

Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndrome is a familial cancer syndrome that results in neuroendocrine tumors. The diagnosis of hereditary PGL/PCC syndrome is based on physical examination, family history, imaging studies, biochemical testing, and molecular genetic testing. Symptoms of PGL/PCC result either from mass effects or catecholamine hypersecretion (e.g., sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, palpitations, pallor, and apprehension or anxiety; Klein and Lloyd. GeneReviews. 2009). Paraganglia are a group of neuroendocrine cells that originate from the embryonic neural crest and can secrete catecholamines. In the PGL/PCC syndrome, paraganglia arise in either the paravertebral axis (base of the skull to the pelvis) for paragangliomas or the adrenal medulla for pheochromocytomas (Welander et al. Endocrine-Related Cancer 18:R253–R276, 2011). Sympathetic paragangliomas hypersecrete catecholamines, whereas parasympathetic paragangliomas are most often nonsecretory. Extra-adrenal parasympathetic paragangliomas are located predominantly in the head and neck and most often are nonsecretory. The sympathetic extra-adrenal paragangliomas are generally located in the thorax, abdomen, and pelvis and are usually secretory. Pheochromocytomas typically hypersecrete catecholamines (Klein and Lloyd. GeneReviews. 2009). The prevalence of PGL/PCC tumors in the United States has been estimated to be between 1:2500 to 1:6000 (Chen et al. Pancreas 39:775–783, 2010) and for the hereditary PGL/PCC syndrome has been estimated at 1:25,000 to 1:50,000 (Welander et al., 2011).

Genetics

Hereditary paraganglioma-pheochromocytoma syndrome is an autosomal dominant disorder and is mainly caused by variants in three genes, (SDHD, SDHC, and SDHB), which are known by their syndromic names PGL1, PGL3, and PGL4. Hereditary PGL/PCC syndrome presents variable expressivity and age-related penetrance. SDHA, SDHB, SDHC, and SDHD are nuclear genes that encode the four subunits of the mitochondrial enzyme succinate dehydrogenase (SDH). Another gene, SDHAF2 (also known as SDH5) encodes a protein that appears to be required for flavination of the SDHA subunit. Variants in SDHD demonstrate parent-of-origin effects and generally cause disease only when the variant is inherited from the father. A proband with a hereditary PGL/PCC syndrome may have inherited the variant from a parent or have a de novo variant. An individual who maternally inherits a SDHD variant has a low risk of developing disease; each of the individual's offspring is at a 50% risk of inheriting the disease-causing allele. An individual who paternally inherits an SDHD variant is at high risk of manifesting paragangliomas and less commonly pheochromocytomas (Kirmani and Young 2012; Welander et al. 2011).

Clinical Sensitivity - Sequencing with CNV PG-Select

Although the majority of PGL/PCC tumors are sporadic (non-familial), approximately 13% of PGL/PCC tumors are caused by germline variants in the known PGL/PCC syndrome genes (Welander et al. Endocrine-Related Cancer 18:R253–R276, 2011). Variants in the SDHD gene are detectable in up to 50% of hereditary PGL/PCC cases depending on the tumor’s location. PGL/PCC tumors can also be found in 10% of other familial syndromes such as multiple endocrine neoplasia type 2 (MEN2), von Hippel–Lindau disease (VHL), and neurofibromatosis type 1 (NF1); they are seen less in Carney triad and Carney–Stratakis syndrome and rarely in multiple endocrine neoplasia type 1 (MEN1; Welander et al., 2011). In addition to the PGL/PCC syndrome genes, germline variants in a number of other genes may also predispose to PGL/PCC tumors (Opocher et al. Best Practice & Research Clinical Endocrinology & Metabolism 24:943–956, 2010). Deletion/duplication frequencies for the SDHD gene are unknown.

Testing Strategy

This test provides full coverage of all coding exons of the SDHD gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Individuals with a history of hereditary PGL/PCC syndrome. People with a family history of hereditary PGL/PCC syndrome should be tested early (<10 years of age). Hereditary PGL/PCC syndrome should be considered in all individuals with paragangliomas or pheochromocytomas, especially those with multiple, multifocal, recurrent or early-onset tumors (i.e., <40 years; Young. Williams Textbook of Endocrinology, 11 ed. pp.:505-537, 2008). This test is specifically designed for heritable germline variants and is not appropriate for the detection of somatic variants in tumor tissue.

Earlier diagnosis may improve patient prognosis through regular screening and treatment for early-onset malignancies. Early detection through surveillance and removal of tumors may prevent or minimize complications related to mass effects, catecholamine hypersecretion, and malignant transformation.

Gene

Official Gene Symbol OMIM ID
SDHD 602690
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

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Citations

  • Chen H, Sippel RS, O’Dorisio MS, Vinik AI, Lloyd RV, Pacak K. 2010. The North American Neuroendocrine Tumor Society Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors: Pheochromocytoma, Paraganglioma, and Medullary Thyroid Cancer. Pancreas 39: 775–783. PubMed ID: 20664475
  • Else et al. 2018. Hereditary Paraganglioma-Pheochromocytoma Syndromes. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301715
  • Opocher G, Schiavi F. 2010. Genetics of pheochromocytomas and paragangliomas. Best Practice & Research Clinical Endocrinology & Metabolism 24: 943–956. PubMed ID: 21115163
  • Welander J, Soderkvist P, Gimm O. 2011. Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas. Endocrine Related Cancer 18: R253–R276. PubMed ID: 22041710
  • Young. Williams Textbook of Endocrinology, 11 ed. Pp.:505-37, 2008

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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