A Contemporary Clinical Approach to Genetic Testing for Heritable Hyperparathyroidism Syndromes

Overview

Journal Endocrine

Specialty Endocrinology

Date 2021 Nov 13

PMID 34773560

Citations 5

Authors

Sunita M C De Sousa

Richard W Carroll

Alex Henderson

John Burgess

Roderick J Clifton-Bligh

Affiliations

Soon will be listed here.

Abstract

Purpose: The improved access and affordability of next generation sequencing has facilitated the clinical use of gene panel testing to test concurrently patients for multiple heritable hyperparathyroidism syndromes. However, there is little guidance as to which patients should be selected for gene panel testing and which genes should be included in such panels. In this review, we provide a practical approach to considering, interpreting and managing genetic testing for familial primary hyperparathyroidism (PHPT) syndromes and familial hypocalciuric hypercalcaemia (FHH) in patients with PTH-dependent hypercalcaemia. We discuss known genes implicated in PHPT and FHH, testing criteria and yields, pre-test counselling, laboratory considerations, and post-test management.

Methods: In addition to reviewing the literature, we conducted audits of local genetic testing data to examine the real-world yield of genetic testing in patients with PTH-dependent hypercalcaemia.

Results: Our local audits revealed a positive genetic testing rate of 15-26% in patients with suspected hyperparathyroidism syndromes.

Conclusion: Based on the particular testing criteria met, affected patients should be tested for variants in the genes currently implicated in PHPT (MEN1, CDC73, RET, CDKN1B, GCM2, CASR) and/or FHH (CASR, GNA11, AP2S1). Patients should be provided with pre- and post-test counselling, including consideration of potential implications for family members.

Citing Articles

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, Gene-Related Tumors, and Insulin Resistance.

Carsote M, Nistor C, Gheorghe A, Sima O, Trandafir A, Nistor T Int J Mol Sci. 2024; 25(12).

PMID: 38928056 PMC: 11203827. DOI: 10.3390/ijms25126349.

Insights into Hyperparathyroidism-Jaw Tumour Syndrome: From Endocrine Acumen to the Spectrum of Gene and Parafibromin-Deficient Tumours.

Gheorghe A, Sima O, Florescu A, Ciuche A, Nistor C, Sandru F Int J Mol Sci. 2024; 25(4).

PMID: 38396977 PMC: 10889221. DOI: 10.3390/ijms25042301.

Genetic testing for familial hyperparathyroidism: clinical-genetic profile in a Mediterranean cohort.

Mazarico-Altisent I, Capel I, Baena N, Bella-Cueto M, Barcons S, Guirao X Front Endocrinol (Lausanne). 2023; 14:1244361.

PMID: 37810884 PMC: 10558207. DOI: 10.3389/fendo.2023.1244361.

Neuroendocrine Parathyroid Tumors: Quality of Life in Patients with Primary Hyperparathyroidism.

Carsote M, Nistor C, Stanciu M, Popa F, Cipaian R, Popa-Velea O Biomedicines. 2023; 11(7).

PMID: 37509698 PMC: 10377520. DOI: 10.3390/biomedicines11072059.

MEN4, the MEN1 Mimicker: A Case Series of three Phenotypically Heterogenous Patients With Unique CDKN1B Mutations.

Seabrook A, Wijewardene A, De Sousa S, Wong T, Sheriff N, Gill A J Clin Endocrinol Metab. 2022; 107(8):2339-2349.

PMID: 35323929 PMC: 9282358. DOI: 10.1210/clinem/dgac162.

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