J Clin Endocrinol Metab. 2019 Mar 08; doi: 10.1210/jc.2018-02789. Epub 2019 Mar 08.
New Concepts About Familial Isolated Hyperparathyroidism.
The Journal of clinical endocrinology and metabolism
Stephen J Marx
Affiliations
Affiliations
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD.
PMID: 30848815
PMCID: PMC6684304 DOI: 10.1210/jc.2018-02789
Abstract
CONTEXT: Familial isolated hyperparathyroidism (FIHP) is defined as familial primary hyperparathyroidism (FH) without a characteristic extra-parathyroidal feature of a more complex hyperparathyroid syndrome. During 80 years, new concepts of FIHP have been developed within this definition. FIHP has been difficult to study due to small kindreds and mildly symptomatic cases.
EVIDENCE ACQUISITION: Searches were through PubMed for FIHP, other FH syndromes, and the gene(s) mutated in each.
EVIDENCE SYNTHESIS: Within its definition, the current concept of FIHP has clinical and mutational components. It can include incomplete expressions of MEN1 FHH, or HPT-JT or their mutations. Newest concepts of FIHP focus upon kindreds without mutation of either the MEN1, CASR, or CDC73 gene; 17% have germline activating mutation of the gene for the GCM2 transcription factor. Other genes for FIHP will probably be identified shortly. The FIHP kindreds with or without GCM2 mutation contain a median of only 2 cases of PHPT. The small kindred size in both subgroups of FIHP is probably caused low rate of screening among relatives. PHPT in FIHP with GCM2 mutation seems similar to PHPT in MEN1. Persons with FIHP and GCM2 mutation present as adults with mild hypercalcemia and multiple parathyroid tumors.
CONCLUSIONS: The current concept of FIHP led to a focus on small kindreds without mutation of MEN1, CASR, or CDC73. These assisted in the identification of germline activating GCM2 mutations in 17%. There is a need for clinical and mutational characterization in more cases to determine any unique clinical features of FIHP, either with or without mutation of GCM2.
Copyright © 2019 Endocrine Society.
References
- Clin Endocrinol (Oxf). 1999 Feb;50(2):191-6 - PubMed
- J Clin Endocrinol Metab. 2000 Jan;85(1):165-7 - PubMed
- J Clin Endocrinol Metab. 2000 May;85(5):2042-7 - PubMed
- Clin Endocrinol (Oxf). 2000 Aug;53(2):205-11 - PubMed
- Medicine (Baltimore). 2002 Jan;81(1):1-26 - PubMed
- Eur J Endocrinol. 2002 Sep;147(3):313-22 - PubMed
- Nat Genet. 2002 Dec;32(4):676-80 - PubMed
- Ann Intern Med. 1976 Jan;84(1):36-43 - PubMed
- Ann Intern Med. 1954 Apr;40(4):765-73 - PubMed
- Metabolism. 1958 Nov;7(6):671-80 - PubMed
- Ann Intern Med. 1962 Dec;57:963-9 - PubMed
- Henry Ford Hosp Med Bull. 1959 Dec;7:245-8 - PubMed
- J Clin Endocrinol Metab. 2004 Jan;89(1):96-102 - PubMed
- J Med Genet. 2004 Mar;41(3):155-60 - PubMed
- J Clin Endocrinol Metab. 2004 Apr;89(4):1747-52 - PubMed
- J Clin Endocrinol Metab. 2004 Jul;89(7):3208-13 - PubMed
- J Clin Endocrinol Metab. 2004 Aug;89(8):4124-9 - PubMed
- J Intern Med. 2005 Jan;257(1):18-26 - PubMed
- Clin Endocrinol (Oxf). 2006 Feb;64(2):146-52 - PubMed
- Clin Endocrinol (Oxf). 2006 Jul;65(1):9-16 - PubMed
- Ann Surg. 1936 Dec;104(6):971-81 - PubMed
- Surgery. 1948 Dec;24(6):1020-5 - PubMed
- J Clin Endocrinol Metab. 2008 Apr;93(4):1426-32 - PubMed
- J Clin Endocrinol Metab. 2009 May;94(5):1826-34 - PubMed
- Arq Bras Endocrinol Metabol. 2008 Nov;52(8):1211-20 - PubMed
- Cleve Clin Q. 1947 Oct;14(4):246-57 - PubMed
- BMC Med Genet. 2010 Jun 11;11:92 - PubMed
- J Clin Endocrinol Metab. 2012 Sep;97(9):2990-3011 - PubMed
- J Clin Endocrinol Metab. 2013 Feb;98(2):E403-8 - PubMed
- Science. 2013 Feb 22;339(6122):959-61 - PubMed
- Genet Res (Camb). 2013 Aug;95(4):114-20 - PubMed
- Cell. 2013 Sep 26;155(1):27-38 - PubMed
- Semin Diagn Pathol. 2013 Aug;30(3):165-77 - PubMed
- J Bone Miner Metab. 2014 Jul;32(4):351-66 - PubMed
- J Clin Endocrinol Metab. 2014 Oct;99(10):3570-9 - PubMed
- Front Endocrinol (Lausanne). 2015 Jun 09;6:96 - PubMed
- Genome Biol. 2015 Nov 05;16:240 - PubMed
- PLoS Genet. 2016 Feb 29;12(2):e1005888 - PubMed
- J Mol Endocrinol. 2016 Oct;57(3):R127-42 - PubMed
- Am J Hum Genet. 2016 Nov 3;99(5):1034-1044 - PubMed
- Hum Genet. 2017 Sep;136(9):1093-1111 - PubMed
- Endocr Relat Cancer. 2018 Feb;25(2):T29-T39 - PubMed
- Medicine (Baltimore). 1986 Jul;65(4):226-41 - PubMed
- Hum Mutat. 2017 Dec;38(12):1621-1648 - PubMed
- Clin Genet. 2018 Mar;93(3):429-438 - PubMed
- PLoS One. 2017 Oct 16;12(10):e0186485 - PubMed
- J Clin Endocrinol Metab. 2017 Dec 1;102(12):4534-4540 - PubMed
- Surgery. 2018 Jan;163(1):31-34 - PubMed
- J Endocr Soc. 2017 Mar 23;1(5):488-499 - PubMed
- Am J Surg Pathol. 2019 Jan;43(1):35-46 - PubMed
- Int J Endocrinol. 2018 Mar 20;2018:8470642 - PubMed
- J Bone Miner Res. 2019 Jan;34(1):22-37 - PubMed
- J Clin Endocrinol Metab. 2019 Jun 1;104(6):1948-1952 - PubMed
- Am J Med. 1969 Oct;47(4):608-18 - PubMed
- Am J Med. 1967 Nov;43(5):727-34 - PubMed
- Br Med J. 1971 Jul 10;3(5766):87-90 - PubMed
- N Engl J Med. 1982 Aug 12;307(7):416-26 - PubMed
- N Engl J Med. 1982 Feb 4;306(5):257-64 - PubMed
- Medicine (Baltimore). 1981 Nov;60(6):397-412 - PubMed
- Nature. 1993 Dec 9;366(6455):575-80 - PubMed
- J Pediatr. 1977 Feb;90(2):269-72 - PubMed
- QJM. 1996 Sep;89(9):653-69 - PubMed
- World J Surg. 1997 Jan;21(1):22-8; discussion 29 - PubMed
- Science. 1997 Apr 18;276(5311):404-7 - PubMed
- Surgery. 1997 Dec;122(6):1028-33 - PubMed
- Hum Mutat. 1998;11(4):264-9 - PubMed
- J Clin Endocrinol Metab. 1998 Jun;83(6):2114-20 - PubMed
- Am J Hum Genet. 1998 Nov;63(5):1544-9 - PubMed
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