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.
CASR CDC73 CDKN1B MEN1 RET
CASR CDC73 CDKN1B MEN1 RET
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)
Familial hypocalciuric hypercalcemia, jaw tumor hyperparathyroid syndrome, multiple endocrine neoplasia type 1, multiple endocrine neoplasia Type 2, MEN1, MEN1-like, HPT, pituitary and parathyroid tumours, MEN4, hyperparathyroidism, isolated hyperparathyroidism, sporadic parathyroid carcinoma, parathyroid, familial isolated hyperparathyroidism, FIH, familial hypocalciuric hypercalcemia, FHH, neonatal severe hyperparathyroidism, NSHPT, MEN2, MEN2A, MEN2B, RET, pheochromocytoma
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.
|Gene||Condition||HPT risk||Tumor risk||Other 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:
Most individuals with hereditary hyperparathyroidism are followed by an endocrinology specialist and medical management is based on a comprehensive assessment.
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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
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|