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Familial hypocalciuric hypercalcemia 2(FBH2; HHC2)

MedGen UID:
374447
Concept ID:
C1840347
Disease or Syndrome
Synonyms: Familial benign hypercalcemia, type 2; FAMILIAL BENIGN HYPERCALCEMIA, TYPE II; Hypocalciuric hypercalcemia, familial, type II; Hypocalciuric hypercalcemia, type II
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): GNA11 (19p13.3)
 
Monarch Initiative: MONDO:0007792
OMIM®: 145981
Orphanet: ORPHA101049

Definition

Familial hypocalciuric hypercalcemia type II (HHC2) is an autosomal dominant disorder characterized by lifelong elevations of serum calcium concentrations with low urinary calcium excretion and normal circulating parathyroid hormone concentrations in most patients. Patients are generally asymptomatic (summary by Nesbit et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of hypocalciuric hypercalcemia, see HHC1 (145980). [from OMIM]

Clinical features

From HPO
Multiple lipomas
MedGen UID:
677074
Concept ID:
C0745730
Finding
The presence of multiple lipomas (a type of benign tissue made of fatty tissue).
Hypocalciuria
MedGen UID:
9381
Concept ID:
C0020599
Disease or Syndrome
An abnormally decreased calcium concentration in the urine.
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
Parathormone-independent increased renal tubular calcium reabsorption
MedGen UID:
871133
Concept ID:
C4025604
Finding
An increase in the reabsorption of calcium by the renal tubulus that is not associated with increased parathormone levels.
Peptic ulcer
MedGen UID:
45384
Concept ID:
C0030920
Disease or Syndrome
The term peptic ulcer refers to acid peptic injury of the digestive tract, resulting in mucosal break reaching the submucosa. Peptic ulcers are usually located in the stomach or proximal duodenum, but they can also be found in the esophagus or Meckel's diverticulum. Infection with Helicobacter pylori and the use of non steroidal antiinflammatory drugs (NSAIDs) or aspirin are the main risk factors of both gastric and duodenal peptic ulcers.
Chondrocalcinosis
MedGen UID:
154303
Concept ID:
C0553730
Disease or Syndrome
Radiographic evidence of articular calcification that represent calcium pyrophosphate depositions in soft tissue surrounding joints and at the insertions of tendons near joints (Entheses/Sharpey fibers) .
Pancreatitis
MedGen UID:
14586
Concept ID:
C0030305
Disease or Syndrome
The presence of inflammation in the pancreas.
Hypercalcemia
MedGen UID:
5686
Concept ID:
C0020437
Disease or Syndrome
An abnormally increased calcium concentration in the blood.
Hypermagnesemia
MedGen UID:
312005
Concept ID:
C1522135
Finding
An abnormally increased magnesium concentration in the blood.
Primary hyperparathyroidism
MedGen UID:
66354
Concept ID:
C0221002
Disease or Syndrome
A type of hyperparathyroidism caused by a primary abnormality of the parathyroid glands (e.g., adenoma, carcinoma, hyperplasia). Primary hyperparathyroidism is associated with hyercalcemia.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFamilial hypocalciuric hypercalcemia 2

Professional guidelines

PubMed

Mazarico-Altisent I, Capel I, Baena N, Bella-Cueto MR, Barcons S, Guirao X, Pareja R, Muntean A, Arsentales V, Caixàs A, Rigla M
Front Endocrinol (Lausanne) 2023;14:1244361. Epub 2023 Sep 21 doi: 10.3389/fendo.2023.1244361. PMID: 37810884Free PMC Article
Bollerslev J, Rejnmark L, Zahn A, Heck A, Appelman-Dijkstra NM, Cardoso L, Hannan FM, Cetani F, Sikjær T, Formenti AM, Björnsdottir S, Schalin-Jantti C, Belaya Z, Gibb FW, Lapauw B, Amrein K, Wicke C, Grasemann C, Krebs M, Ryhänen EM, Makay O, Minisola S, Gaujoux S, Bertocchio JP, Hassan-Smith ZK, Linglart A, Winter EM, Kollmann M, Zmierczak HG, Tsourdi E, Pilz S, Siggelkow H, Gittoes NJ, Marcocci C, Kamenicky P; 2021 PARAT Working Group
Eur J Endocrinol 2022 Feb 1;186(2):R33-R63. Epub 2022 Jan 13 doi: 10.1530/EJE-21-1044. [Epub ahead of print] PMID: 34863037Free PMC Article
Khairi S, Osborne J, Jacobs MF, Clines GT, Miller BS, Hughes DT, Else T
Horm Cancer 2020 Oct;11(5-6):250-255. Epub 2020 Aug 5 doi: 10.1007/s12672-020-00394-2. PMID: 32761341Free PMC Article

Recent clinical studies

Etiology

Mazarico-Altisent I, Capel I, Baena N, Bella-Cueto MR, Barcons S, Guirao X, Pareja R, Muntean A, Arsentales V, Caixàs A, Rigla M
Front Endocrinol (Lausanne) 2023;14:1244361. Epub 2023 Sep 21 doi: 10.3389/fendo.2023.1244361. PMID: 37810884Free PMC Article
Josephs TM, Zhang F, Dinh LV, Keller AN, Conigrave AD, Capuano B, Gregory KJ, Leach K
J Mol Endocrinol 2022 May 9;69(1):243-257. doi: 10.1530/JME-21-0263. PMID: 35318962
Bollerslev J, Rejnmark L, Zahn A, Heck A, Appelman-Dijkstra NM, Cardoso L, Hannan FM, Cetani F, Sikjær T, Formenti AM, Björnsdottir S, Schalin-Jantti C, Belaya Z, Gibb FW, Lapauw B, Amrein K, Wicke C, Grasemann C, Krebs M, Ryhänen EM, Makay O, Minisola S, Gaujoux S, Bertocchio JP, Hassan-Smith ZK, Linglart A, Winter EM, Kollmann M, Zmierczak HG, Tsourdi E, Pilz S, Siggelkow H, Gittoes NJ, Marcocci C, Kamenicky P; 2021 PARAT Working Group
Eur J Endocrinol 2022 Feb 1;186(2):R33-R63. Epub 2022 Jan 13 doi: 10.1530/EJE-21-1044. [Epub ahead of print] PMID: 34863037Free PMC Article
Hannan FM, Kallay E, Chang W, Brandi ML, Thakker RV
Nat Rev Endocrinol 2018 Dec;15(1):33-51. doi: 10.1038/s41574-018-0115-0. PMID: 30443043Free PMC Article
Hovden S, Rejnmark L, Ladefoged SA, Nissen PH
Eur J Endocrinol 2017 Feb;176(2):177-185. Epub 2016 Nov 15 doi: 10.1530/EJE-16-0842. PMID: 27913609

Diagnosis

Bollerslev J, Rejnmark L, Zahn A, Heck A, Appelman-Dijkstra NM, Cardoso L, Hannan FM, Cetani F, Sikjær T, Formenti AM, Björnsdottir S, Schalin-Jantti C, Belaya Z, Gibb FW, Lapauw B, Amrein K, Wicke C, Grasemann C, Krebs M, Ryhänen EM, Makay O, Minisola S, Gaujoux S, Bertocchio JP, Hassan-Smith ZK, Linglart A, Winter EM, Kollmann M, Zmierczak HG, Tsourdi E, Pilz S, Siggelkow H, Gittoes NJ, Marcocci C, Kamenicky P; 2021 PARAT Working Group
Eur J Endocrinol 2022 Feb 1;186(2):R33-R63. Epub 2022 Jan 13 doi: 10.1530/EJE-21-1044. [Epub ahead of print] PMID: 34863037Free PMC Article
Vannucci L, Brandi ML
Front Horm Res 2019;51:52-62. Epub 2018 Nov 19 doi: 10.1159/000491038. PMID: 30641521
Lee JY, Shoback DM
Best Pract Res Clin Endocrinol Metab 2018 Oct;32(5):609-619. Epub 2018 May 26 doi: 10.1016/j.beem.2018.05.004. PMID: 30449544Free PMC Article
Marx SJ
J Clin Endocrinol Metab 2017 Nov 1;102(11):3933-3936. doi: 10.1210/jc.2017-01606. PMID: 28945857Free PMC Article
Endres DB
Clin Biochem 2012 Aug;45(12):954-63. Epub 2012 May 5 doi: 10.1016/j.clinbiochem.2012.04.025. PMID: 22569596

Therapy

Goldsweig B, Turk Yilmaz RS, Ravindranath Waikar A, Brownstein C, Carpenter TO
J Bone Miner Res 2024 Sep 26;39(10):1406-1411. doi: 10.1093/jbmr/zjae137. PMID: 39163488
Koca SB
Turk J Pediatr 2023;65(5):853-861. doi: 10.24953/turkjped.2022.1040. PMID: 37853976
Josephs TM, Zhang F, Dinh LV, Keller AN, Conigrave AD, Capuano B, Gregory KJ, Leach K
J Mol Endocrinol 2022 May 9;69(1):243-257. doi: 10.1530/JME-21-0263. PMID: 35318962
Hannan FM, Kallay E, Chang W, Brandi ML, Thakker RV
Nat Rev Endocrinol 2018 Dec;15(1):33-51. doi: 10.1038/s41574-018-0115-0. PMID: 30443043Free PMC Article
Marx SJ
J Clin Endocrinol Metab 2017 Nov 1;102(11):3933-3936. doi: 10.1210/jc.2017-01606. PMID: 28945857Free PMC Article

Prognosis

English KA, Lines KE, Thakker RV
Hormones (Athens) 2024 Mar;23(1):3-14. Epub 2023 Dec 1 doi: 10.1007/s42000-023-00508-9. PMID: 38038882Free PMC Article
Bollerslev J, Rejnmark L, Zahn A, Heck A, Appelman-Dijkstra NM, Cardoso L, Hannan FM, Cetani F, Sikjær T, Formenti AM, Björnsdottir S, Schalin-Jantti C, Belaya Z, Gibb FW, Lapauw B, Amrein K, Wicke C, Grasemann C, Krebs M, Ryhänen EM, Makay O, Minisola S, Gaujoux S, Bertocchio JP, Hassan-Smith ZK, Linglart A, Winter EM, Kollmann M, Zmierczak HG, Tsourdi E, Pilz S, Siggelkow H, Gittoes NJ, Marcocci C, Kamenicky P; 2021 PARAT Working Group
Eur J Endocrinol 2022 Feb 1;186(2):R33-R63. Epub 2022 Jan 13 doi: 10.1530/EJE-21-1044. [Epub ahead of print] PMID: 34863037Free PMC Article
Vannucci L, Brandi ML
Front Horm Res 2019;51:52-62. Epub 2018 Nov 19 doi: 10.1159/000491038. PMID: 30641521
Lee JY, Shoback DM
Best Pract Res Clin Endocrinol Metab 2018 Oct;32(5):609-619. Epub 2018 May 26 doi: 10.1016/j.beem.2018.05.004. PMID: 30449544Free PMC Article
Hannan FM, Kallay E, Chang W, Brandi ML, Thakker RV
Nat Rev Endocrinol 2018 Dec;15(1):33-51. doi: 10.1038/s41574-018-0115-0. PMID: 30443043Free PMC Article

Clinical prediction guides

Koca SB
Turk J Pediatr 2023;65(5):853-861. doi: 10.24953/turkjped.2022.1040. PMID: 37853976
Mazarico-Altisent I, Capel I, Baena N, Bella-Cueto MR, Barcons S, Guirao X, Pareja R, Muntean A, Arsentales V, Caixàs A, Rigla M
Front Endocrinol (Lausanne) 2023;14:1244361. Epub 2023 Sep 21 doi: 10.3389/fendo.2023.1244361. PMID: 37810884Free PMC Article
Howles SA, Gorvin CM, Cranston T, Rogers A, Gluck AK, Boon H, Gibson K, Rahman M, Root A, Nesbit MA, Hannan FM, Thakker RV
J Bone Miner Res 2023 Jun;38(6):907-917. Epub 2023 Apr 18 doi: 10.1002/jbmr.4803. PMID: 36970776Free PMC Article
Chinoy A, Nicholson J, Skae M, Hannan FM, Thakker RV, Mughal MZ, Padidela R
J Pediatr 2023 Jun;257:113367. Epub 2023 Mar 2 doi: 10.1016/j.jpeds.2023.02.013. PMID: 36868303
Bollerslev J, Rejnmark L, Zahn A, Heck A, Appelman-Dijkstra NM, Cardoso L, Hannan FM, Cetani F, Sikjær T, Formenti AM, Björnsdottir S, Schalin-Jantti C, Belaya Z, Gibb FW, Lapauw B, Amrein K, Wicke C, Grasemann C, Krebs M, Ryhänen EM, Makay O, Minisola S, Gaujoux S, Bertocchio JP, Hassan-Smith ZK, Linglart A, Winter EM, Kollmann M, Zmierczak HG, Tsourdi E, Pilz S, Siggelkow H, Gittoes NJ, Marcocci C, Kamenicky P; 2021 PARAT Working Group
Eur J Endocrinol 2022 Feb 1;186(2):R33-R63. Epub 2022 Jan 13 doi: 10.1530/EJE-21-1044. [Epub ahead of print] PMID: 34863037Free PMC Article

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