Familial Isolated Hyperparathyroidism (FIHP)

Familial Isolated Hyperparathyroidism (FIHP), a disorder characterized by parathyroid adenoma/hyperplasia in the absence other associated endocrinopathies. In some cases, individuals with FIHP also develop parathyroid carcinoma. FIHP is genetically heterogeneous and can be caused by mutations in the MEN1, HRPT2, or CASR genes.

Tests Available

Forms and Documents

Test Details

CASR
  • Distinguish FHH from primary hyperparathyroidism and other disorders of calcium homeostasis
  • Confirmation of a clinical diagnosis
  • To determine appropriate treatment, including avoidance of parathyroidectomy in FHH patients
  • Prenatal diagnosis in pregnancies at-risk for NSHPT
  • Capillary Sequencing

Ordering

170
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81405x1
No
Yes
  • 275.4 Disorders of calcium metabolism
* For price inquiries please email zebras@genedx.com

References

  1. Pollak et al., (1993) Cell 75:1297-1303
  2. Chou et al., (1995) Am J Hum Genet 56:1075-1079
  3. Pearce et al., (1995) J Clin Invest 96:2683-2692
  4. Pearce et al., (1996) NEJM 335(15):1115-1122
  5. Hendy et al., (2000) Hum Mut 16:281-296
  6. Hendy et al.,(2003) J of Clin Endocrin & Metab 88(8):3674-3681
  7. Warner et al., (2004) J Med Genet 41(3):155-60
  8. Lienhardt et al (2001) J Clin Endocr Metab 86:5313-5323
  9. Thakker (2004) Cell Calcium 35:275-28
  10. Gunn et al (2004) Ann Clin Biochem 41:441-58
  11. Simonds et al., (2002) Medicine (Baltimore) 81:1-26

Forms and Documents

Test Details

CDC73 (HRPT2)
  • Confirm the clinical diagnosis of HPT-JT
  • Determine the genetic etiology of FIHP
  • Identification of germline mutations in patients with apparent sporadic parathyroid carcinoma
  • Differentiation between HPT-JT and other familial endocrine neoplasia syndromes with parathyroid involvement (i.e., multiple endocrine neoplasia type I caused by mutations in the MEN1 gene and multiple endocrine neoplasia type 2 caused by mutations in the RET gene)
  • Identification of relatives at risk for parathyroid malignancy and the clinical manifestations of HPT-JT
  • Establishment of a medical management plan (including surveillance for parathyroid tumors, ossifying tumors, and renal cysts) for at-risk individuals
  • Capillary Sequencing

Ordering

173
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 753.1 Cystic kidney disease Excludes: acquired cyst of kidney (593.2)
  • 252 Disorders of parathyroid gland Excludes: hungry bone syndrome (275.5)
  • 213.1 Lower jaw bone
  • v18.1 Other endocrine and metabolic diseases
  • 194.1 Parathyroid gland
  • 227.1 Parathyroid gland
* For price inquiries please email zebras@genedx.com

References

  1. Carpten, J. D. et al., HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nature Genet. 32: 676-80, 2002
  2. Shattuck, T. et al., Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med. 349: 1722-9, 2003
  3. Villablanca, A. et al., Germline and de novo mutations in the HRPT2 tumour suppressor gene in familial isolated hyperparathyroidism (FIHP). J Med Genet. 41: e32, 2004
  4. Warner, J. et al., Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications. J Med Genet. 41: 155-60, 2004
  5. Mizusawa, N. et al., Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumour syndrome. Clin Endocrinol. 65: 9-16, 2006

Forms and Documents

Test Details

CDC73 (HRPT2)
  • Confirm the clinical diagnosis of HPT-JT
  • Determine the genetic etiology of FIHP
  • Identification of germline mutations in patients with apparent sporadic parathyroid carcinoma
  • Differentiation between HPT-JT and other familial endocrine neoplasia syndromes with parathyroid involvement (i.e., multiple endocrine neoplasia type I caused by mutations in the MEN1 gene and multiple endocrine neoplasia type 2 caused by mutations in the RET gene)
  • Identification of relatives at risk for parathyroid malignancy and the clinical manifestations of HPT-JT
  • Establishment of a medical management plan (including surveillance for parathyroid tumors, ossifying tumors, and renal cysts) for at-risk individuals
  • Capillary Sequencing

Ordering

1732
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 753.1 Cystic kidney disease Excludes: acquired cyst of kidney (593.2)
  • 252 Disorders of parathyroid gland Excludes: hungry bone syndrome (275.5)
  • 213.1 Lower jaw bone
  • v18.1 Other endocrine and metabolic diseases
  • 194.1 Parathyroid gland
  • 227.1 Parathyroid gland
* For price inquiries please email zebras@genedx.com

References

  1. Warner, J. et al., Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications. J Med Genet. 41: 155-60, 2004
  2. Mizusawa, N. et al., Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumour syndrome. Clin Endocrinol. 65: 9-16, 2006
  3. Villablanca, A. et al., Germline and de novo mutations in the HRPT2 tumour suppressor gene in familial isolated hyperparathyroidism (FIHP). J Med Genet. 41: e32, 2004
  4. Shattuck, T. et al., Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med. 349: 1722-9, 2003
  5. Carpten, J. D. et al., HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nature Genet. 32: 676-80, 2002

Forms and Documents

Test Details

CDC73 (HRPT2)
  • Confirm the clinical diagnosis of HPT-JT
  • Determine the genetic etiology of FIHP
  • Identification of germline mutations in patients with apparent sporadic parathyroid carcinoma
  • Differentiation between HPT-JT and other familial endocrine neoplasia syndromes with parathyroid involvement (i.e., multiple endocrine neoplasia type I caused by mutations in the MEN1 gene and multiple endocrine neoplasia type 2 caused by mutations in the RET gene)
  • Identification of relatives at risk for parathyroid malignancy and the clinical manifestations of HPT-JT
  • Establishment of a medical management plan (including surveillance for parathyroid tumors, ossifying tumors, and renal cysts) for at-risk individuals
  • Capillary Sequencing

Ordering

1731
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 753.1 Cystic kidney disease Excludes: acquired cyst of kidney (593.2)
  • 252 Disorders of parathyroid gland Excludes: hungry bone syndrome (275.5)
  • 213.1 Lower jaw bone
  • v18.1 Other endocrine and metabolic diseases
  • 194.1 Parathyroid gland
  • 227.1 Parathyroid gland
* For price inquiries please email zebras@genedx.com

References

  1. Mizusawa, N. et al., Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumour syndrome. Clin Endocrinol. 65: 9-16, 2006
  2. Warner, J. et al., Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications. J Med Genet. 41: 155-60, 2004
  3. Villablanca, A. et al., Germline and de novo mutations in the HRPT2 tumour suppressor gene in familial isolated hyperparathyroidism (FIHP). J Med Genet. 41: e32, 2004
  4. Carpten, J. D. et al., HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nature Genet. 32: 676-80, 2002
  5. Shattuck, T. et al., Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med. 349: 1722-9, 2003

Forms and Documents

Test Details

MEN1
  • Confirmation of a clinical diagnosis
  • To differentiate MEN1-related FIHP from other causes (mutations in CASR or HRPT2 genes)
  • Identification of at-risk family members
  • To determine appropriate surveillance and treatment protocols
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

176
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81405x1
Yes
Yes
  • 227 Benign neoplasm of other endocrine glands and related structures Use additional code to identify any functional activity Excludes: ovary (220) pancreas (211.6) testis (222.0)
  • 227.1 Parathyroid gland
  • 227.3 Pituitary gland and craniopharyngeal duct (pouch), Craniobuccal pouch, Hypophysis Rathke's pouch, Sella turcica
* For price inquiries please email zebras@genedx.com

References

  1. Pannett, AA. et al. Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial isolated primary hyperparathyroidism. Clin Endocrinol. 58:639-646, 2003
  2. Warner, J. et al. Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications. J Med Genet. 41:155-160, 2004
  3. Villablanca, A. et al. Involvement of the MEN1 locus in familial isolated hyperparathyroidism. Eur J Endocrinol. 147: 313-322, 2002
  4. Klein, RD. et al. Clinical testing for multiple endocrine neoplasia type 1 in a DNA diagnostic laboratory. Genet Med. 7:131-138, 2005
  5. Cavaco, BM. et al., Mutational analysis of Portuguese families with multiple endocrine neoplasia type 1 reveals large germline deletions. Clin Endocrinol. 56:465-473, 2002
  6. Bergman, L. et al., Identification of MEN1 gene mutations in families with MEN1 and related disorders. Br J Cancer. 62:1009-1014, 2000
  7. Giraud, S. et al., Germ-Line Mutation Analysis in Patients with Multiple Endocrine Neoplasia Type 1 and Related Disorders. Am J Hum Genet. 63: 455-467, 1998
  8. Bassett J.H.D., et al., Characterization of Mutations in Patients with Multiple Endocrine Neoplasia Type 1. Am J Hum Genet. 62: 232- 244, 1998
  9. Agarwal S. et al., Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type1 and related states. Hum Mol Genet. 6: 1169-1175, 1997

Forms and Documents

Test Details

CDC73 (HRPT2)
  • An individual with primary hyperparathyroidism and ossifying fibroma(s) of the jaw
  • An individual with early-onset primary hyperparathyroidism (age <45 years)
  • Children diagnosed with ossifying fibroma(s) of the maxilla or mandible
  • An individual with sporadic and/or early-onset parathyroid carcinoma or adenoma
  • An individual with primary hyperparathyroidism or ossifying jaw fibromas and a personal or family history of features associated with Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT) such as renal cysts or tumors
  • Familial primary hyperparathyroidism with negative genetic testing for multiple endocrine neoplasia type 1 (MEN1)
  • An unaffected individual with a family history suggestive of CDC73 related conditions (see above) when an affected individual is unavailable for his or her own genetic testing.
  • Capillary Sequencing
  • Exon Array CGH

Ordering

721
3 weeks
2-5 mL Blood - Lavender Top Tube
Buccal Swab | Fibroblasts (separate charge for cell culture may apply) | Oral Rinse

Billing

81479x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Masi et al., (2008) Endocr Relat Cancer 15(4):1115-1126.
  2. Carpten, J. D. et al., (2002) Nature Genet 32: 676-80.
  3. Shattuck, T. et al., (2003) N Engl J Med 349: 1722-9.
  4. Villablanca, A. et al., (2004) J Med Genet 41: e32.
  5. Warner, J. et al., (2004)J Med Genet 41: 155-60.
  6. Mizusawa, N. et al., (2006) Clin Endocrinol 65: 9-16.
  7. Cascon et al., (2011) Genes Chromosomes Cancer 50(11):922-929.
  8. Domingues et al., (2012) Clin Endocrinol 76(1):33-38.

Forms and Documents

Test Details

MEN1
  • An individual with a personal and/or family history of tumors associated with multiple endocrine neoplasia, type I (MEN1) especially parathyroid tumors, gastro-entero-pancreatic neuroendocrine tumors, and anterior pituitary tumors. Other common features include adrenocortical and carcinoid tumors, facial angiofibromas, collagenomas, ependymomas, leiomyomas, lipomas, and meningiomas
  • An individual with multiple primary or multi-focal endocrine tumors
  • An individual with a personal and/or family history of isolated parathyroid tumors concerning for familial isolated hyperparathyroidism (FIHP) which may be associated with pathogenic variants in the MEN1 gene, among others
  • An unaffected individual with a family history suggestive of MEN1 (see above) when an affected individual is unavailable for his or her own genetic testing
  • Capillary Sequencing
  • MLPA

Ordering

719
3 weeks
2-5 mL Blood - Lavender Top Tube
Buccal Swab | Fibroblasts (separate charge for cell culture may apply) | Oral Rinse

Billing

81405x1, 81404x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Agarwal S. et al., Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type1 and related states. Hum Mol Genet. 6: 1169-1175, 1997
  2. Bassett J.H.D., et al., Characterization of Mutations in Patients with Multiple Endocrine Neoplasia Type 1. Am J Hum Genet. 62: 232- 244, 1998
  3. Giraud, S. et al., Germ-Line Mutation Analysis in Patients with Multiple Endocrine Neoplasia Type 1 and Related Disorders. Am J Hum Genet. 63: 455-467, 1998
  4. Bergman, L. et al., Identification of MEN1 gene mutations in families with MEN1 and related disorders. Br J Cancer. 62:1009-1014, 2000
  5. Cavaco, BM. et al., Mutational analysis of Portuguese families with multiple endocrine neoplasia type 1 reveals large germline deletions. Clin Endocrinol. 56:465-473, 2002
  6. Klein, RD. et al. Clinical testing for multiple endocrine neoplasia type 1 in a DNA diagnostic laboratory. Genet Med. 7:131-138, 2005
  7. Warner, J. et al. Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications. J Med Genet. 41:155-160, 2004
  8. Villablanca, A. et al. Involvement of the MEN1 locus in familial isolated hyperparathyroidism. Eur J Endocrinol. 147: 313-322, 2002
  9. Pannett, AA. et al. Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial isolated primary hyperparathyroidism. Clin Endocrinol. 58:639-646, 2003.

Forms and Documents

Test Details

MEN1
  • Confirmation of a clinical diagnosis
  • To differentiate MEN1-related FIHP from other causes (mutations in CASR or HRPT2 genes)
  • Identification of at-risk family members
  • To determine appropriate surveillance and treatment protocols
  • Prenatal diagnosis
  • MLPA

Ordering

906
3-4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81404x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Pannett, AA. et al. Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial isolated primary hyperparathyroidism. Clin Endocrinol. 58:639-646, 2003
  2. Villablanca, A. et al. Involvement of the MEN1 locus in familial isolated hyperparathyroidism. Eur J Endocrinol. 147: 313-322, 2002
  3. Warner, J. et al. Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications. J Med Genet. 41:155-160, 2004
  4. Klein, RD. et al. Clinical testing for multiple endocrine neoplasia type 1 in a DNA diagnostic laboratory. Genet Med. 7:131-138, 2005
  5. Cavaco, BM. et al., Mutational analysis of Portuguese families with multiple endocrine neoplasia type 1 reveals large germline deletions. Clin Endocrinol. 56:465-473, 2002
  6. Bergman, L. et al., Identification of MEN1 gene mutations in families with MEN1 and related disorders. Br J Cancer. 62:1009-1014, 2000
  7. Giraud, S. et al., Germ-Line Mutation Analysis in Patients with Multiple Endocrine Neoplasia Type 1 and Related Disorders. Am J Hum Genet. 63: 455-467, 1998
  8. Bassett J.H.D., et al., Characterization of Mutations in Patients with Multiple Endocrine Neoplasia Type 1. Am J Hum Genet. 62: 232- 244, 1998
  9. Agarwal S. et al., Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type1 and related states. Hum Mol Genet. 6: 1169-1175, 1997