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Autosomal dominant hypocalcemia 2(HYPOC2)

MedGen UID:
815573
•Concept ID:
C3809243
•
Disease or Syndrome
Synonyms: HYPOC2; HYPOCALCEMIA, AUTOSOMAL DOMINANT 2
 
Gene (location): GNA11 (19p13.3)
 
Monarch Initiative: MONDO:0014146
OMIM®: 615361

Definition

An autosomal dominant hypocalcemia disease that has material basis in heterozygous mutation in the GNA11 gene on chromosome 19p13. [from MONDO]

Clinical features

From HPO
Postnatal growth retardation
MedGen UID:
395343
•Concept ID:
C1859778
•
Finding
Slow or limited growth after birth.
See: Feature record | Search on this feature
Paresthesia
MedGen UID:
14619
•Concept ID:
C0030554
•
Disease or Syndrome
Abnormal sensations such as tingling, pricking, or numbness of the skin with no apparent physical cause.
See: Feature record | Search on this feature
Muscle spasm
MedGen UID:
52431
•Concept ID:
C0037763
•
Sign or Symptom
Sudden and involuntary contractions of one or more muscles.
See: Feature record | Search on this feature
Basal ganglia calcification
MedGen UID:
234651
•Concept ID:
C1389280
•
Pathologic Function
The presence of calcium deposition affecting one or more structures of the basal ganglia.
See: Feature record | Search on this feature
Hypocalcemia
MedGen UID:
5705
•Concept ID:
C0020598
•
Disease or Syndrome
An abnormally decreased calcium concentration in the blood.
See: Feature record | Search on this feature
Abnormal blood phosphate concentration
MedGen UID:
867643
•Concept ID:
C4022032
•
Finding
An abnormality of phosphate homeostasis or concentration in the body.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Genetic Screening in a Large Chinese Cohort of Childhood Onset Hypoparathyroidism by Next-Generation Sequencing Combined with TBX1-MLPA.
Wang Y, Nie M, Wang O, Li Y, Jiang Y, Li M, Xia W, Xing X
J Bone Miner Res 2019 Dec;34(12):2254-2263. Epub 2019 Nov 13 doi: 10.1002/jbmr.3854. PMID: 31433868
GENETICS IN ENDOCRINOLOGY: Gain and loss of function mutations of the calcium-sensing receptor and associated proteins: current treatment concepts.
Mayr B, Schnabel D, Dörr HG, Schöfl C
Eur J Endocrinol 2016 May;174(5):R189-208. Epub 2015 Dec 8 doi: 10.1530/EJE-15-1028. PMID: 26646938

Recent clinical studies

Etiology

Autosomal Dominant Hypocalcemia Type 1: A Systematic Review.
Roszko KL, Stapleton Smith LM, Sridhar AV, Roberts MS, Hartley IR, Gafni RI, Collins MT, Fox JC, Nemeth EF
J Bone Miner Res 2022 Oct;37(10):1926-1935. Epub 2022 Aug 22 doi: 10.1002/jbmr.4659. PMID: 35879818Free PMC Article
Lack of GNAS Remethylation During Oogenesis May Be a Cause of Sporadic Pseudohypoparathyroidism Type Ib.
Milioto A, Reyes M, Hanna P, Kiuchi Z, Turan S, Zeve D, Agarwal C, Grigelioniene G, Chen A, Mericq V, Frangos M, Ten S, Mantovani G, Salusky IB, Tebben P, Jüppner H
J Clin Endocrinol Metab 2022 Mar 24;107(4):e1610-e1619. doi: 10.1210/clinem/dgab830. PMID: 34791361Free PMC Article
Progression of PTH Resistance in Autosomal Dominant Pseudohypoparathyroidism Type Ib Due to Maternal STX16 Deletions.
Kiuchi Z, Reyes M, Hanna P, Sharma A, DeClue T, Olney RC, Tebben P, Jüppner H
J Clin Endocrinol Metab 2022 Jan 18;107(2):e681-e687. doi: 10.1210/clinem/dgab660. PMID: 34477200Free PMC Article
Phenotypic spectrum of neonatal CHARGE syndrome.
Sánchez N, Hernández M, Cruz JP, Mellado C
Rev Chil Pediatr 2019 Oct;90(5):533-538. doi: 10.32641/rchped.v90i5.1080. PMID: 31859737
The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases.
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

Diagnosis

Barakat syndrome.
Berkešová BA, Borbély Z
Vnitr Lek 2023 Summer;69(E-3):16-19. doi: 10.36290/vnl.2023.036. PMID: 37468331
Autosomal Dominant Hypocalcemia Type 1: A Systematic Review.
Roszko KL, Stapleton Smith LM, Sridhar AV, Roberts MS, Hartley IR, Gafni RI, Collins MT, Fox JC, Nemeth EF
J Bone Miner Res 2022 Oct;37(10):1926-1935. Epub 2022 Aug 22 doi: 10.1002/jbmr.4659. PMID: 35879818Free PMC Article
Diseases associated with calcium-sensing receptor.
Vahe C, Benomar K, Espiard S, Coppin L, Jannin A, Odou MF, Vantyghem MC
Orphanet J Rare Dis 2017 Jan 25;12(1):19. doi: 10.1186/s13023-017-0570-z. PMID: 28122587Free PMC Article
Familial hypocalciuric hypercalcemia and calcium sensing receptor.
Mrgan M, Nielsen S, Brixen K
Acta Clin Croat 2014 Jun;53(2):220-5. PMID: 25163238
Inherited disorders of renal magnesium handling.
Cole DEC, Quamme GA
J Am Soc Nephrol 2000 Oct;11(10):1937-1947. doi: 10.1681/ASN.V11101937. PMID: 11004227

Therapy

Autosomal Dominant Hypocalcemia Type 1: A Systematic Review.
Roszko KL, Stapleton Smith LM, Sridhar AV, Roberts MS, Hartley IR, Gafni RI, Collins MT, Fox JC, Nemeth EF
J Bone Miner Res 2022 Oct;37(10):1926-1935. Epub 2022 Aug 22 doi: 10.1002/jbmr.4659. PMID: 35879818Free PMC Article
Treatment of Autosomal Dominant Hypocalcemia Type 1 With the Calcilytic NPSP795 (SHP635).
Roberts MS, Gafni RI, Brillante B, Guthrie LC, Streit J, Gash D, Gelb J, Krusinska E, Brennan SC, Schepelmann M, Riccardi D, Bin Khayat ME, Ward DT, Nemeth EF, Rosskamp R, Collins MT
J Bone Miner Res 2019 Sep;34(9):1609-1618. Epub 2019 Jul 26 doi: 10.1002/jbmr.3747. PMID: 31063613Free PMC Article
Long-Term Parathyroid Hormone 1-34 Replacement Therapy in Children with Hypoparathyroidism.
Winer KK, Kelly A, Johns A, Zhang B, Dowdy K, Kim L, Reynolds JC, Albert PS, Cutler GB Jr
J Pediatr 2018 Dec;203:391-399.e1. doi: 10.1016/j.jpeds.2018.08.010. PMID: 30470382Free PMC Article
The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases.
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
Gα(11) mutation in mice causes hypocalcemia rectifiable by calcilytic therapy.
Gorvin CM, Hannan FM, Howles SA, Babinsky VN, Piret SE, Rogers A, Freidin AJ, Stewart M, Paudyal A, Hough TA, Nesbit MA, Wells S, Vincent TL, Brown SD, Cox RD, Thakker RV
JCI Insight 2017 Feb 9;2(3):e91103. doi: 10.1172/jci.insight.91103. PMID: 28194447Free PMC Article

Prognosis

GNA11 Variants Identified in Patients with Hypercalcemia or Hypocalcemia.
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
Progression of PTH Resistance in Autosomal Dominant Pseudohypoparathyroidism Type Ib Due to Maternal STX16 Deletions.
Kiuchi Z, Reyes M, Hanna P, Sharma A, DeClue T, Olney RC, Tebben P, Jüppner H
J Clin Endocrinol Metab 2022 Jan 18;107(2):e681-e687. doi: 10.1210/clinem/dgab660. PMID: 34477200Free PMC Article
Treatment of Autosomal Dominant Hypocalcemia Type 1 With the Calcilytic NPSP795 (SHP635).
Roberts MS, Gafni RI, Brillante B, Guthrie LC, Streit J, Gash D, Gelb J, Krusinska E, Brennan SC, Schepelmann M, Riccardi D, Bin Khayat ME, Ward DT, Nemeth EF, Rosskamp R, Collins MT
J Bone Miner Res 2019 Sep;34(9):1609-1618. Epub 2019 Jul 26 doi: 10.1002/jbmr.3747. PMID: 31063613Free PMC Article
The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases.
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
Dominant isolated renal magnesium loss is caused by misrouting of the Na+,K+-ATPase gamma-subunit.
Meij IC, Koenderink JB, De Jong JC, De Pont JJ, Monnens LA, Van Den Heuvel LP, Knoers NV
Ann N Y Acad Sci 2003 Apr;986:437-43. doi: 10.1111/j.1749-6632.2003.tb07226.x. PMID: 12763862

Clinical prediction guides

GNA11 Variants Identified in Patients with Hypercalcemia or Hypocalcemia.
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
Autosomal Dominant Hypocalcemia Type 1: A Systematic Review.
Roszko KL, Stapleton Smith LM, Sridhar AV, Roberts MS, Hartley IR, Gafni RI, Collins MT, Fox JC, Nemeth EF
J Bone Miner Res 2022 Oct;37(10):1926-1935. Epub 2022 Aug 22 doi: 10.1002/jbmr.4659. PMID: 35879818Free PMC Article
Differential parathyroid and kidney Ca(2+)-sensing receptor activation in autosomal dominant hypocalcemia 1.
van Megen WH, Tan RSG, Alexander RT, Dimke H
EBioMedicine 2022 Apr;78:103947. Epub 2022 Mar 18 doi: 10.1016/j.ebiom.2022.103947. PMID: 35313217Free PMC Article
Expanding the clinical and genetic spectrum of pathogenic variants in STIM1.
Ticci C, Cassandrini D, Rubegni A, Riva B, Vattemi G, Matà S, Ricci G, Baldacci J, Guglielmi V, Di Muzio A, Malandrini A, Tonin P, Siciliano G, Federico A, Genazzani AA, Santorelli FM, Merlini L
Muscle Nerve 2021 Nov;64(5):567-575. Epub 2021 Aug 26 doi: 10.1002/mus.27391. PMID: 34368974
Treatment of Autosomal Dominant Hypocalcemia Type 1 With the Calcilytic NPSP795 (SHP635).
Roberts MS, Gafni RI, Brillante B, Guthrie LC, Streit J, Gash D, Gelb J, Krusinska E, Brennan SC, Schepelmann M, Riccardi D, Bin Khayat ME, Ward DT, Nemeth EF, Rosskamp R, Collins MT
J Bone Miner Res 2019 Sep;34(9):1609-1618. Epub 2019 Jul 26 doi: 10.1002/jbmr.3747. PMID: 31063613Free PMC Article

Recent systematic reviews

Autosomal Dominant Hypocalcemia Type 1: A Systematic Review.
Roszko KL, Stapleton Smith LM, Sridhar AV, Roberts MS, Hartley IR, Gafni RI, Collins MT, Fox JC, Nemeth EF
J Bone Miner Res 2022 Oct;37(10):1926-1935. Epub 2022 Aug 22 doi: 10.1002/jbmr.4659. PMID: 35879818Free PMC Article

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      Clinical tests in GTR
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