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Autosomal dominant osteopetrosis

MedGen UID:
1378401
•Concept ID:
C4272579
•
Disease or Syndrome
Synonyms: Autosomal Dominant Osteopetrosis; autosomal dominant osteopetrosis; autosomal dominant osteopetrosis (disease); OPTA; osteopetrosis (disease), autosomal dominant
 
Related genes: LRP5, CLCN7
 
Monarch Initiative: MONDO:0020645
OMIM® Phenotypic series: PS607634

Definition

An autosomal dominant form of osteopetrosis due to mutation(s) in the CLCN7 gene, encoding H(+)/Cl(-) exchange transporter 7. Clinical features include sclerosis involving the spine, the pelvis, and the base of the skull. Complications can include optic nerve compression, dental abscesses, anemia, and bone fragility. One third of individuals who carry a CLCN7 mutation have a normal skeletal phenotype. [from NCI]

Professional guidelines

PubMed

Osteopetroses, emphasizing potential approaches to treatment.
Teti A, Econs MJ
Bone 2017 Sep;102:50-59. Epub 2017 Feb 4 doi: 10.1016/j.bone.2017.02.002. PMID: 28167345
Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment.
Del Fattore A, Peruzzi B, Rucci N, Recchia I, Cappariello A, Longo M, Fortunati D, Ballanti P, Iacobini M, Luciani M, Devito R, Pinto R, Caniglia M, Lanino E, Messina C, Cesaro S, Letizia C, Bianchini G, Fryssira H, Grabowski P, Shaw N, Bishop N, Hughes D, Kapur RP, Datta HK, Taranta A, Fornari R, Migliaccio S, Teti A
J Med Genet 2006 Apr;43(4):315-25. Epub 2005 Aug 23 doi: 10.1136/jmg.2005.036673. PMID: 16118345Free PMC Article

Recent clinical studies

Etiology

Natural History of Type II Autosomal Dominant Osteopetrosis: A Single Center Retrospective Study.
Wang Z, Li X, Wang Y, Fu W, Liu Y, Zhang Z, Wang C
Front Endocrinol (Lausanne) 2022;13:819641. Epub 2022 Mar 17 doi: 10.3389/fendo.2022.819641. PMID: 35370969Free PMC Article
Novel CLCN7 mutations cause autosomal dominant osteopetrosis type II and intermediate autosomal recessive osteopetrosis.
Li L, Lv SS, Wang C, Yue H, Zhang ZL
Mol Med Rep 2019 Jun;19(6):5030-5038. Epub 2019 Apr 3 doi: 10.3892/mmr.2019.10123. PMID: 30942407
Osteopetroses, emphasizing potential approaches to treatment.
Teti A, Econs MJ
Bone 2017 Sep;102:50-59. Epub 2017 Feb 4 doi: 10.1016/j.bone.2017.02.002. PMID: 28167345
Autosomal-dominant osteopetrosis: an incidental finding.
Rajathi M, Austin RD, Mathew P, Bharathi CS, Srivastava KC
Indian J Dent Res 2010 Oct-Dec;21(4):611-4. doi: 10.4103/0970-9290.74234. PMID: 21187637
Osteopetrosis.
Stark Z, Savarirayan R
Orphanet J Rare Dis 2009 Feb 20;4:5. doi: 10.1186/1750-1172-4-5. PMID: 19232111Free PMC Article

Diagnosis

Transcriptomic and bioinformatic analysis of Clcn7-dependent Autosomal Dominant Osteopetrosis type 2. Preclinical and clinical implications.
Norwood I, Szondi D, Ciocca M, Coudert A, Cohen-Solal M, Rucci N, Teti A, Maurizi A
Bone 2021 Mar;144:115828. Epub 2020 Dec 28 doi: 10.1016/j.bone.2020.115828. PMID: 33359007
Autosomal-dominant osteopetrosis: an incidental finding.
Rajathi M, Austin RD, Mathew P, Bharathi CS, Srivastava KC
Indian J Dent Res 2010 Oct-Dec;21(4):611-4. doi: 10.4103/0970-9290.74234. PMID: 21187637
Osteopetrosis.
Stark Z, Savarirayan R
Orphanet J Rare Dis 2009 Feb 20;4:5. doi: 10.1186/1750-1172-4-5. PMID: 19232111Free PMC Article
Sclerosing bone disorders.
de Vernejoul MC
Best Pract Res Clin Rheumatol 2008 Mar;22(1):71-83. doi: 10.1016/j.berh.2007.12.011. PMID: 18328982
Autosomal dominant osteopetrosis.
Bollerslev J, Mosekilde L
Clin Orthop Relat Res 1993 Sep;(294):45-51. PMID: 8358946

Therapy

Effect of Roflumilast, a Selective PDE4 Inhibitor, on Bone Phenotypes in ADO2 Mice.
Alam I, Hardman SL, Gerard-O'Riley RL, Acton D, Parker RS, Hong JM, Bruzzaniti A, Econs MJ
Calcif Tissue Int 2024 Apr;114(4):419-429. Epub 2024 Feb 1 doi: 10.1007/s00223-023-01180-2. PMID: 38300304
Interferon Gamma-1b Does Not Increase Markers of Bone Resorption in Autosomal Dominant Osteopetrosis.
Imel EA, Liu Z, Acton D, Coffman M, Gebregziabher N, Tong Y, Econs MJ
J Bone Miner Res 2019 Aug;34(8):1436-1445. Epub 2019 May 13 doi: 10.1002/jbmr.3715. PMID: 30889272Free PMC Article
Bone Mineral Density and Microarchitecture in Patients With Autosomal Dominant Osteopetrosis: A Report of Two Cases.
Arruda M, Coelho MC, Moraes AB, de Paula Paranhos-Neto F, Madeira M, Farias ML, Vieira Neto L
J Bone Miner Res 2016 Mar;31(3):657-62. Epub 2015 Oct 20 doi: 10.1002/jbmr.2715. PMID: 26387875
Autosomal dominant type I osteopetrosis is related with iatrogenic fractures in arthroplasty.
van Hove RP, de Jong T, Nolte PA
Clin Orthop Surg 2014 Dec;6(4):484-8. Epub 2014 Nov 10 doi: 10.4055/cios.2014.6.4.484. PMID: 25436076Free PMC Article
Autosomal dominant osteopetrosis revisited: lessons from recent studies.
Bollerslev J, Henriksen K, Nielsen MF, Brixen K, Van Hul W
Eur J Endocrinol 2013 Aug;169(2):R39-57. Epub 2013 Jul 13 doi: 10.1530/EJE-13-0136. PMID: 23744590

Prognosis

Autosomal Dominant Osteopetrosis (ADO) Caused by a Missense Variant in the TCIRG1 Gene.
Jodeh W, Katz AJ, Hart M, Warden SJ, Niziolek P, Alam I, Ing S, Polgreen LE, Imel EA, Econs MJ
J Clin Endocrinol Metab 2024 Jun 17;109(7):1726-1732. doi: 10.1210/clinem/dgae040. PMID: 38261998Free PMC Article
A Mild Case of Autosomal Recessive Osteopetrosis Masquerading as the Dominant Form Involving Homozygous Deep Intronic Variations in the CLCN7 Gene.
Hofstaetter JG, Atkins GJ, Kato H, Kogawa M, Blouin S, Misof BM, Roschger P, Evdokiou A, Yang D, Solomon LB, Findlay DM, Ito N
Calcif Tissue Int 2022 Oct;111(4):430-444. Epub 2022 May 26 doi: 10.1007/s00223-022-00988-8. PMID: 35618777Free PMC Article
Natural History of Type II Autosomal Dominant Osteopetrosis: A Single Center Retrospective Study.
Wang Z, Li X, Wang Y, Fu W, Liu Y, Zhang Z, Wang C
Front Endocrinol (Lausanne) 2022;13:819641. Epub 2022 Mar 17 doi: 10.3389/fendo.2022.819641. PMID: 35370969Free PMC Article
Novel mutations of CLCN7 cause autosomal dominant osteopetrosis type II (ADOII) and intermediate autosomal recessive osteopetrosis (ARO) in seven Chinese families.
Zhang X, Wei Z, He J, Wang C, Zhang Z
Postgrad Med 2017 Nov;129(8):934-942. Epub 2017 Oct 11 doi: 10.1080/00325481.2017.1386529. PMID: 28975865
Novel CLCN7 mutation identified in a Han Chinese family with autosomal dominant osteopetrosis-2.
Deng H, He D, Rong P, Xu H, Yuan L, Li L, Lu Q, Guo Y
Mol Pain 2016;12 Epub 2016 Jun 20 doi: 10.1177/1744806916652628. PMID: 27325559Free PMC Article

Clinical prediction guides

Transcriptomic and bioinformatic analysis of Clcn7-dependent Autosomal Dominant Osteopetrosis type 2. Preclinical and clinical implications.
Norwood I, Szondi D, Ciocca M, Coudert A, Cohen-Solal M, Rucci N, Teti A, Maurizi A
Bone 2021 Mar;144:115828. Epub 2020 Dec 28 doi: 10.1016/j.bone.2020.115828. PMID: 33359007
Radiographic imaging, densitometry and disease severity in Autosomal dominant osteopetrosis type 2.
Ladd LM, Imel EA, Niziolek PJ, Liu Z, Warden SJ, Liang Y, Econs MJ
Skeletal Radiol 2021 May;50(5):903-913. Epub 2020 Oct 3 doi: 10.1007/s00256-020-03625-3. PMID: 33009917Free PMC Article
Novel CLCN7 mutations cause autosomal dominant osteopetrosis type II and intermediate autosomal recessive osteopetrosis.
Li L, Lv SS, Wang C, Yue H, Zhang ZL
Mol Med Rep 2019 Jun;19(6):5030-5038. Epub 2019 Apr 3 doi: 10.3892/mmr.2019.10123. PMID: 30942407
Clinical Significance of DXA and HR-pQCT in Autosomal Dominant Osteopetrosis (ADO II).
Butscheidt S, Rolvien T, Kornak U, Schmidt FN, Schinke T, Amling M, Oheim R
Calcif Tissue Int 2018 Jan;102(1):41-52. Epub 2017 Oct 10 doi: 10.1007/s00223-017-0332-x. PMID: 29018903
Human osteopetrosis and other sclerosing disorders: recent genetic developments.
de Vernejoul MC, Bénichou O
Calcif Tissue Int 2001 Jul;69(1):1-6. Epub 2001 Jun 5 doi: 10.1007/s002230020046. PMID: 11685426

Recent systematic reviews

Maxillary osteomyelitis associated with osteopetrosis: Systematic review.
Carvalho PHA, Moura LB, Real Gabrielli MF, Cabrini Gabrielli MA, Antonio Pereira Filho V
J Craniomaxillofac Surg 2018 Nov;46(11):1905-1910. Epub 2018 Sep 24 doi: 10.1016/j.jcms.2018.09.004. PMID: 30309794

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