J Med Genet 41:155-160 doi:10.1136/jmg.2003.016725
  • Original article

Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications

  1. J Warner1,2,
  2. M Epstein3,
  3. A Sweet1,2,
  4. D Singh2,
  5. J Burgess4,
  6. S Stranks5,
  7. P Hill6,
  8. D Perry-Keene2,7,
  9. D Learoyd8,
  10. B Robinson8,
  11. P Birdsey9,
  12. E Mackenzie1,
  13. B T Teh10,
  14. J B Prins1,2,
  15. J Cardinal1
  1. 1Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Ipswich Rd, Woolloongabba 4102, Qld, Australia
  2. 2University of Queensland, 4072, Qld, Australia
  3. 3John Hunter Hospital, Newcastle, 2300, NSW, Australia
  4. 4Department of Medicine, University of Tasmania, Hobart, Tas., Australia
  5. 5Ashford Medical Center, Ashford, SA, Australia
  6. 6Wickham Tce, Brisbane, Qld, Australia
  7. 7Department of Endocrinology, Royal Brisbane Hospital, Qld, Australia
  8. 8Department of Endocrinology and Cancer Genetics, Kolling Institute, Royal North Shore Hospital and University of Sydney, NSW, Australia
  9. 9Midhurst Ave, Christie Downs, 5164, SA, Australia
  10. 10Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI, USA
  1. Correspondence to:
 Prof J B Prins
 Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Ipswich Rd, Woolloongabba, 4102, Qld, Australia;
  • Received 21 November 2003
  • Accepted 21 November 2003


Familial hyperparathyroidism is not uncommon in clinical endocrine practice. It encompasses a spectrum of disorders including multiple endocrine neoplasia types 1 (MEN1) and 2A, hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric hypercalcaemia (FHH), and familial isolated hyperparathyroidism (FIHP). Distinguishing among the five syndromes is often difficult but has profound implications for the management of patient and family. The availability of specific genetic testing for four of the syndromes has improved diagnostic accuracy and simplified family monitoring in many cases but its current cost and limited accessibility require rationalisation of its use. No gene has yet been associated exclusively with FIHP. FIHP phenotypes have been associated with mutant MEN1 and calcium-sensing receptor (CASR) genotypes and, very recently, with mutation in the newly identified HRPT2 gene. The relative proportions of these are not yet clear. We report results of MEN1, CASR, and HRPT2 genotyping of 22 unrelated subjects with FIHP phenotypes. We found 5 (23%) with MEN1 mutations, four (18%) with CASR mutations, and none with an HRPT2 mutation. All those with mutations had multiglandular hyperparathyroidism. Of the subjects with CASR mutations, none were of the typical FHH phenotype. These findings strongly favour a recommendation for MEN1 and CASR genotyping of patients with multiglandular FIHP, irrespective of urinary calcium excretion. However, it appears that HRPT2 genotyping should be reserved for cases in which other features of the HPT-JT phenotype have occurred in the kindred. Also apparent is the need for further investigation to identify additional genes associated with FIHP.