• Test code: 01303
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Hyperparathyroidism Panel

Test description

The Invitae Hyperparathyroidism Panel analyzes five genes associated with hereditary hyperparathyroidism (HPT). These genes were curated based on the available evidence to date and provide Invitae’s most comprehensive test for individuals and families with features of HPT.

Individuals with a pathogenic variant in one of the genes on this panel have a higher risk of developing parathyroid disease—a disease that can be difficult both to detect and to treat. Prolonged parathyroid disease can also cause other health issues that may result in serious complications. It can be extremely helpful to identify those who are at high risk so that additional screening, surveillance, and interventions can be initiated—both for parathyroid disease and for other health issues, including certain cancers. These efforts can result in risk-reduction and early diagnosis, which may increase the chances of successful treatment and survival.

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Primary panel (5 genes)
  • CASR-related disorders
  • CDC73-related disorders
  • CDKN1B-related disorders
  • hyperparathyroidism jaw tumor syndrome
  • MEN1-related disorders
  • multiple endocrine neoplasia type 1 (MEN1)
  • multiple endocrine neoplasia type 2A (MEN2A)
  • multiple endocrine neoplasia type 2B (MEN2B)
  • multiple endocrine neoplasia type 4 (MEN4)

In the United States, approximately 100,000 people develop hyperparathyroidism (HPT) each year. HPT is twice as common in women than in men, and the risk increases with age. Approximately 1 in 500 women over age 60 will develop HPT. Approximately 5% of HPT cases are familial (inherited). It is unknown if hyperparathyroidism and parathyroid adenomas may predispose to cancer. Parathyroid carcinoma is a very rare cancer, with very few cases reported. There is an increased risk of parathyroid carcinoma in CDC73 mutations.

Individuals with a pathogenic variant in one of these genes have an increased risk of malignancy compared to the average person, but not everyone with such a variant will actually develop cancer. Further, the same variant can present differently, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may benefit most patients who are found to have a pathogenic variant. For gene-associated cancer risks, see the table below.

GeneConditionHPT riskTumor riskOther associated cancers/features
CASR CASR- related conditions up to 100% parathyroid adenomas
CDC73 hyperparathyroidism jaw tumor syndrome 80% by age 40 parathyroid cancer—10%–15% lifetime risk ossifying jaw tumors, hamartomas, renal cysts, Wilms tumor, uterine fibroids
CDKN1B multiple endocrine neoplasia type 4 (MEN4) elevated parathyroid adenomas pituitary adenomas, pancreatic NETs tumors
MEN1 multiple endocrine neoplasia type 1 (MEN1) up to 100% (PMID: 9904212) parathyroid adenomas pituitary adenomas, pancreatic NETs tumors, carcinoids, benign thyroid lesions, meningioma, lipoma, adrenocortical carcinoma—1%–13% lifetime risk (22084155)
RET multiple endocrine neoplasia type 2A (MEN2A), multiple endocrine neoplasia type 2B (MEN2B) elevated parathyroid hyperplasia—20%–30% lifetime risk (PMID: 24899893) medullary thyroid cancer, pheochromocytomas, MEN2B-distinctive facies, and intestinal ganglioneuromas

Most of the genes on this panel confer an increased risk of developing hyperparathyroidism in an autosomal dominant inheritance pattern. CASR mutations can be inherited in autosomal dominant and autosomal recessive inheritance pattern.

Invitae’s hyperparathyroidism panel may be considered for individuals with the following:

  • hyperparathyroidism with low urine calcium excretion
  • early onset hyperparathyroidism
  • a family history of hypercalcemia
  • ossifying fibroma(s) of the maxilla or mandible
  • parathyroid carcinoma

  1. Giusti, F, et al. Multiple Endocrine Neoplasia Type 1. 2005 Aug 31. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1538/ PMID: 20301710
  2. Thakker, RV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J. Clin. Endocrinol. Metab. 2012; 97(9):2990-3011. doi: 10.1210/jc.2012-1230. PMID: 22723327
  3. Shibata, Y, et al. Early-onset, severe, and recurrent primary hyperparathyroidism associated with a novel CDC73 mutation. Endocr. J. 2015; 62(7):627-32. doi: 10.1507/endocrj.EJ15-0057. PMID: 25959515
  4. Wang, TT, et al. Two cases of multiple ossifying fibromas in the jaws. Diagn Pathol. 2014; 9:75. doi: 10.1186/1746-1596-9-75. PMID: 24678936
  5. Falchetti, A, et al. Multiple endocrine neoplasia type 1 (MEN1): not only inherited endocrine tumors. Genet. Med. 2009; 11(12):825-35. doi: 10.1097/GIM.0b013e3181be5c97. PMID: 19904212
  6. Vergés, B, et al. Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. J. Clin. Endocrinol. Metab. 2002; 87(2):457-65. doi: 10.1210/jcem.87.2.8145. PMID: 11836268
  7. Thakker, RV. Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4). Mol. Cell. Endocrinol. 2014; 386(1-2):2-15. doi: 10.1016/j.mce.2013.08.002. PMID: 23933118
  8. Bradley, KJ, et al. Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour syndrome. J. Intern. Med. 2005; 257(1):18-26. doi: 10.1111/j.1365-2796.2004.01421.x. PMID: 15606373
  9. Iacobone, M, et al. Hyperparathyroidism-jaw tumor syndrome: a report of three large kindred. Langenbecks Arch Surg. 2009; 394(5):817-25. doi: 10.1007/s00423-009-0511-y. PMID: 19529956
  10. Parfitt, J, et al. Tumor suppressor gene mutation in a patient with a history of hyperparathyroidism-jaw tumor syndrome and healed generalized osteitis fibrosa cystica: a case report and genetic pathophysiology review. J. Oral Maxillofac. Surg. 2015; 73(1):194.e1-9. doi: 10.1016/j.joms.2014.09.008. PMID: 25511968
  11. Jackson, MA, et al. CDC73-Related Disorders. 2008 Dec 31. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK3789/ PMID: 20301744
  12. Ellard, S, et al. Detection of an MEN1 gene mutation depends on clinical features and supports current referral criteria for diagnostic molecular genetic testing. Clin. Endocrinol. (Oxf). 2005; 62(2):169-75. doi: 10.1111/j.1365-2265.2005.02190.x. PMID: 15670192
  13. Gatta-Cherifi, B, et al. Adrenal involvement in MEN1. Analysis of 715 cases from the Groupe d'etude des Tumeurs Endocrines database. Eur. J. Endocrinol. 2012; 166(2):269-79. doi: 10.1530/EJE-11-0679. PMID: 22084155
  14. Berna, MJ, et al. Serum gastrin in Zollinger-Ellison syndrome: II. Prospective study of gastrin provocative testing in 293 patients from the National Institutes of Health and comparison with 537 cases from the literature. evaluation of diagnostic criteria, proposal of new criteria, and correlations with clinical and tumoral features. Medicine (Baltimore). 2006; 85(6):331-64. doi: 10.1097/MD.0b013e31802b518c. PMID: 17108779
  15. Asgharian, B, et al. Cutaneous tumors in patients with multiple endocrine neoplasm type 1 (MEN1) and gastrinomas: prospective study of frequency and development of criteria with high sensitivity and specificity for MEN1. J. Clin. Endocrinol. Metab. 2004; 89(11):5328-36. doi: 10.1210/jc.2004-0218. PMID: 15531478
  16. Thim, SB, et al. Activating calcium-sensing receptor gene variants in children: a case study of infant hypocalcaemia and literature review. Acta Paediatr. 2014; 103(11):1117-25. PMID: 25039540
  17. Warner, J, et al. Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications. J. Med. Genet. 2004; 41(3):155-60. PMID: 14985373
  18. Christensen, SE, et al. Familial hypocalciuric hypercalcaemia: a review. Curr Opin Endocrinol Diabetes Obes. 2011; 18(6):359-70. PMID: 21986511
  19. Pannett, AA, Thakker, RV. Multiple endocrine neoplasia type 1. Endocr. Relat. Cancer. 1999; 6(4):449-73. PMID: 10730900

Most individuals with hereditary hyperparathyroidism are followed by an endocrinology specialist and medical management is based on a comprehensive assessment.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CASR NM_000388.3
CDC73 NM_024529.4
CDKN1B NM_004064.4
MEN1 NM_130799.2
RET NM_020975.4