Primary hyperparathyroidism is characterised by hypercalcaemia, inappropriately high parathyroid hormone (PTH) levels and isolated parathyroid tumours. Hereditary primary hyperparathyroidism may develop as a solitary endocrinopathy or as part of the Multiple Endocrine Neoplasia type 1 (MEN1) or hereditary hyperparathyroidism-jaw tumour (HPT-JT) syndromes.
How to order genomic testing for primary hyperparathyroidism
This page provides information for healthcare professionals on how to request non-NHS genomic testing for primary hyperparathyroidism. For NHS tests, please visit the relevant pages here.
Step by step instructions
About primary hyperparathyroidism
Primary hyperparathyroidism is characterised by hypercalcaemia, inappropriately high parathyroid hormone (PTH) levels and isolated parathyroid tumours. Hereditary primary hyperparathyroidism may develop as a solitary endocrinopathy or as part of the Multiple Endocrine Neoplasia type 1 (MEN1) or hereditary hyperparathyroidism-jaw tumour (HPT-JT) syndromes.
MEN1 disease-causing variants have been reported in 20-57% of families with familial isolated hyperparathyroidism (Villablanca et al 2002 Eur J Endocrinol 147:313-322; Pannett et al 2003 Clin Endocrinol 58:639-646). Inactivating variants of CDC73 (formerly known as HRPT2), account for approximately 14% of familial isolated hyperparathyroidism cases and 50% of HPT-JT cases (Cascon et al 2011 Genes Chromosomes and Cancer 50:922-929). Inactivating variants in the CASR gene cause primary hyperparathyroidism and Familial hypocalciuric hypercalcaemia (FHH). Variants in CASR account for approximately 15-18% of Familial Isolated Hyperparathyroidism cases (Warner et al 2004 J Med Genet 41:155-160).
Familial Hypocalciuric Hypercalcaemia (FHH) is an autosomal dominant disorder characterised by elevated serum calcium concentrations with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone level.
FHH type 1 is caused by disease-causing variants in the CASR gene, FHH type 2 is caused by disease-causing variants in the GNA11 gene and FHH type 3 is caused by disease-causing variants in the AP2S1 gene. Pathogenic variants in AP2S1, CASR and GNA11 genes account for more than 75% cases of Familial Hypocalciuric Hypercalcaemia (Alberto et al 2018 Best Pract Res Clin Endocrinol Metab 32:781-790).
Test code and gene information
NHSE test directory code: R151 Familial hyperparathyroidism or Familial Hypocalciuric Hypercalcaemia.
AP2S1, CASR, CDC73, CDKN1B, GNA11, MEN1 and RET gene analysis in familial isolated hyperparathyroidism and familial hypocalciuric hypercalcaemia.
Eligibility
Eligibility criteria for genomic tests can be found in the National Genomic Test Directory.
This lists the clinical specialties that would be expected to request for a given clinical indication and sets out which patients should be considered for testing.
Test order form
All samples for genomic testing should be accompanied by a fully completed request form.
The request form should include as much clinical information about the patient or family member, family relationships and the requested test code (R number). All request forms must indicate either a specific disorder/gene(s) to be investigated or, a request to extract and store DNA.
This form should be used for the majority of test requests.
Please do not download and store this on your desktop or system. The form is regularly updated. Our recommendation is to save or bookmark a link to our website to ensure you are working with the most up-do-date version.
Download the latest version here: GMS Test Order Form v2.3
Consent
An appropriate discussion of genomic testing and the possible implications for a patient and their family members must take place before testing is requested.
It is the referring clinician’s responsibility to ensure that the patient/carer knows the purpose of the test and that the sample may be stored for future diagnostic testing. In submitting a sample with a request form, the clinician confirms that informed consent has been obtained for (a) testing and storage (indefinitely) (b) the use of this sample and the information generated from it to be shared with members of the donor’s family and their health professionals (if appropriate). The patient should be advised that the samples may be used anonymously for quality assurance and training purposes.
If stated as a requirement for a specific test, a record of this discussion must be retained within the patient record when a genomic test is ordered.
For more information please view the Consent and Confidentiality in Genomic Medicine guidelines from the Joint Committee on Medical Genetics.
Samples and transport
Before sending samples for genomic testing, please ensure you follow the correct preparation and transport guidelines. This includes information on sample types, volumes, handling, labelling, and packaging standards.
For a full list of sample requirements and transport guidance, please visit the samples and transport page of the website.
Results and turnaround times
Turnaround times (TATs) for genomic tests are continually refined through ongoing reviews of testing standards.
Results will be returned to the email account or clinician listed on the request form.
Important resources
AMEND is a registered charity offering support for patients with MEN types 1 and 2, and associated sporadic growths. Click here to view their website.
The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.