NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020.

Cover of GeneReviews®

GeneReviews® [Internet].

Show details

Multicentric Osteolysis Nodulosis and Arthropathy

Synonyms: Nodulosis-Arthropathy-Osteolysis Syndrome, Torg Syndrome, Torg-Winchester Syndrome

, MSc, , MS, , MD, DM, and , MD, DM.

Author Information

Initial Posting: .

Estimated reading time: 13 minutes

Summary

Clinical characteristics.

Multicentric osteolysis nodulosis and arthropathy (MONA) is a skeletal dysplasia characterized by progressive osteolysis (particularly of the carpal and tarsal bones), osteoporosis, subcutaneous nodules on the palms and soles, and progressive arthropathy (joint contractures, pain, swelling, and stiffness). Other manifestations include coarse facies, pigmented skin lesions, cardiac defects, and corneal opacities. Onset is usually between ages six months and six years (range: birth to 11 years).

Diagnosis/testing.

The diagnosis of MONA is established in a proband with characteristic clinical and radiographic findings and either biallelic pathogenic variants in MMP2 or decreased activity of the enzyme matrix metalloproteinase 2.

Management.

Treatment of manifestations: Treatment is supportive only and can include physical therapy (which may slow the rate of development of contractures and prolong mobility). Pain medications may not provide relief. Congenital heart defects are managed as per routine.

Surveillance: Annual reviews by a rheumatologist for pain management and joint assessments.

Genetic counseling.

MONA is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the MMP2 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal testing and preimplantation genetic diagnosis for a pregnancy at increased risk are possible.

Diagnosis

Formal diagnostic criteria have not been established for multicentric osteolysis nodulosis and arthropathy (MONA).

Suggestive Findings

MONA should be suspected in individuals with the following clinical and radiographic findings:

Clinical

  • Joint disease manifest predominantly as pain, swelling, and contractures of the small joints of the hands and feet in early childhood (Figure 1, Figure 2)
  • Subcutaneous nodules, usually on the palms and soles (Figure 2)
  • Coarse facial features
  • Gingival hypertrophy
Figure 1. . Hands of different children with MONA showing joint contractures and swelling of the digits at age 4 years (A), 5 years (B), 7 years (C,D), 9 years (E), 10 years (F), 13 years (G,H), and 15 years (I).

Figure 1.

Hands of different children with MONA showing joint contractures and swelling of the digits at age 4 years (A), 5 years (B), 7 years (C,D), 9 years (E), 10 years (F), 13 years (G,H), and 15 years (I). From Bhavani et al [2016]; republished with permission (more...)

Figure 2. . Feet of different individuals with MONA at ages 5 years (A), 6 years (B,C), 7 years (D,E), 9 years (F), 10 years (G), 13 years (H,I), and 15 years (J).

Figure 2.

Feet of different individuals with MONA at ages 5 years (A), 6 years (B,C), 7 years (D,E), 9 years (F), 10 years (G), 13 years (H,I), and 15 years (J). Subcutaneous nodules are seen in A, B, C, F, G (arrows). From Bhavani et al [2016]; republished with (more...)

Radiographic

  • Progressive osteopenia and osteolysis with early and predominant involvement of the bones of the hands (Figure 4) and feet (Figure 5). The carpal and tarsal bones, which are initially well formed, slowly show thinning of the cortices, osteopenia, and finally osteolysis, becoming small and irregular or disappearing completely.
  • Thin cortices of the long bones (Figure 6). The metacarpals, metatarsals, and phalanges are most affected.
  • Milder and similar changes in other bones
Figure 4. . Radiographs of the hands of different children with MONA at age 4 years (A), 5 years (B), 6 years (C,D), 7 years (E), 9 years (F), 10 years (G), 11 years (H), and 13 years (I,J).

Figure 4.

Radiographs of the hands of different children with MONA at age 4 years (A), 5 years (B), 6 years (C,D), 7 years (E), 9 years (F), 10 years (G), 11 years (H), and 13 years (I,J). All have diffuse osteopenia and cortical thinning, most striking in the (more...)

Figure 5. . Radiographs of the feet of affected individuals at ages 5 years (A), 6 years (B), 7 years (C), 9 years (D), and 13 years (E).

Figure 5.

Radiographs of the feet of affected individuals at ages 5 years (A), 6 years (B), 7 years (C), 9 years (D), and 13 years (E). All cases demonstrate diffuse osteopenia. Small tarsal bones for age with irregular margins, particularly in (C) and (E), are (more...)

Figure 6. . Radiographs of the long bones of the upper extremities in affected individuals at ages 6 years (A, B) and 13 years (C, D, E).

Figure 6.

Radiographs of the long bones of the upper extremities in affected individuals at ages 6 years (A, B) and 13 years (C, D, E). All cases demonstrate decreased bone mineralization with cortical thinning. From Bhavani et al [2016]; republished with permission (more...)

Establishing the Diagnosis

The diagnosis of MONA is established in a proband with characteristic clinical and radiographic findings by identification of biallelic pathogenic variants in MMP2 on molecular genetic testing (see Table 1) or decreased activity of the enzyme matrix metalloproteinase 2 by gelatin zymography.

Molecular genetic testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing:

  • Single-gene testing. Sequence analysis of MMP2 is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found.
  • A multigene panel that includes MMP2 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
    For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
  • More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered if single-gene testing (and/or use of a multigene panel that includes MMP2) fails to confirm a diagnosis in an individual with features of MONA. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Table 1.

Molecular Genetic Testing Used in Multicentric Osteolysis Nodulosis and Arthropathy

Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
MMP2Sequence analysis 327/28 4
Gene-targeted deletion/duplication analysis 5Unknown 6
1.
2.

See Molecular Genetics for information on allelic variants detected in this gene.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.
5.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

6.

No data on detection rate of gene-targeted deletion/duplication analysis are available.

Analysis of matrix metalloproteinase 2 enzyme activity can be performed by the electrophoretic technique gelatin zymography on body fluids and/or cell or tissue extracts [Martignetti et al 2001, Azzollini et al 2014]. In contrast to controls, affected individuals show complete loss of enzyme activity.

Clinical Characteristics

Clinical Description

Multicentric osteolysis nodulosis and arthropathy (MONA) is a skeletal dysplasia characterized by progressive osteolysis (particularly of the carpal and tarsal bones), osteoporosis, subcutaneous nodules on the palms and soles, and progressive arthropathy (contractures, pain, joint swelling/stiffness). Other manifestations include pigmented lesions on the skin, coarse facies, corneal opacities, and cardiac defects.

Most affected children are apparently normal at birth. Onset is usually between ages six months and six years [Azzollini et al 2014]; the range is from birth to 11 years [Castberg et al 2013, Bhavani et al 2016].

Joints. Peripheral joints are more involved than proximal joints. Small joints of the hands and feet are the most obvious sites of involvement. Progressive bone destruction leads to pain, swelling, stiffness, and later flexion contractures (Figure 1, Figure 2). Foot and hand deformities and progressive shortening of digits occur with age.

Knees show swelling and contractures in the majority (Figure 3); hip involvement is less severe [Bhavani et al 2016].

Figure 3. . Swollen knee joints in children with MONA at age 6 years (A), 7 years (B), and 13 years (C,D).

Figure 3.

Swollen knee joints in children with MONA at age 6 years (A), 7 years (B), and 13 years (C,D). Note serpiginous hyperpigmented skin lesions in C and D. From Bhavani et al [2016]; republished with permission of John Wiley and Sons

Wrists, ankles, and elbows are also involved.

Over time all affected individuals need assistance with mobility. Those with more severe manifestations are wheelchair bound between ages three and 12 years [Zankl et al 2005, Rouzier et al 2006, Temtamy et al 2012].

Face. Coarsening of facial features, bulbous nose, proptosis, strabismus, and gingival hypertrophy have been observed in several affected individuals [Bhavani et al 2016].

Skin. Subcutaneous, firm, palpable nodules in the palms and soles are noted in the majority of (but not all) affected individuals (Figures 2B and 2C). The presence of subcutaneous nodules may be age dependent. To date it has not been possible to determine if these nodules are painful as affected individuals have pain in their hands and feet due to osteopenia, fractures, contractures, limitation of movement, and sometimes inflammation.

Other cutaneous manifestations include hyperpigmentation and thickening. Serpiginous hyperpigmented cutaneous lesions are present in a few individuals (Figures 3C and 3D) [Zankl et al 2005, Azzollini et al 2014, Bhavani et al 2016].

In some individuals excessive skin folds in the hands and feet have resulted from destruction of underlying bones (Figure 1I).

Heart. Congenital heart defects (transposition of great arteries, atrial septal defect, ventricular septal defect, bicuspid aortic valve, and mitral valve prolapse) have been observed in one third of individuals reported to date [Tuysuz et al 2009, Castberg et al 2013, Bhavani et al 2016].

Other

Genotype-Phenotype Correlations

No genotype-phenotype correlations have been observed.

Nomenclature

In addition to MONA, this phenotype has been reported in the literature as Torg syndrome, Winchester-Torg (or Torg-Winchester) syndrome, and nodulosis-arthropathy-osteolysis (NAO) syndrome. All of these conditions have been shown to be caused by biallelic pathogenic variants in MMP2 with no discernable genotype-phenotype correlation. The term MONA is therefore used throughout this GeneReview to refer to all of these conditions.

Prevalence

The prevalence for this rare skeletal dysplasia is not available at present. To date 44 individuals (from 27 families) with molecularly proven MONA have been reported.

Differential Diagnosis

Table 2.

Disorders to Consider in the Differential Diagnosis of Multicentric Osteolysis Nodulosis and Arthropathy (MONA)

Differential Diagnosis DisorderGeneMOIClinical Features of the Differential Diagnosis Disorder
Overlapping w/MONADistinguishing from MONA
Juvenile
idiopathic
arthritis
Joint pain, swelling, & stiffness
  • Joint inflammation (tenderness & warmth)
  • ↑ erythrocyte sedimentation rate & C-reactive protein (minimal in some instances)
Winchester syndrome (OMIM 277950)MMP14 1ARSimilar phenotypeNone
Multicentric carpal tarsal osteolysis w/
& w/out nephropathy (OMIM 166300)
MAFBAD
  • Osteolysis of carpal & tarsal bones
  • Joint swelling
  • Onset in infancy
  • Nephropathy (not always present)
  • Phalanges less affected
Hyaline fibromatosis
syndrome
(OMIM 228600)
ANTXR2AR
  • Skin thickening
  • Coarse facies
  • Osteopenia & osteolysis
  • Similar early manifestations in some
  • Hyaline deposits in papillary dermis & other tissues
  • Pearly papules of face & neck; perianal masses
  • Differing pattern of bone involvement
Familial
expansile
osteolysis
(OMIM 174810)
TNFRSF11AADOsteolysis
  • Hearing loss
  • Early loss of dentition
  • Bowing of long bones
  • ↑ serum alkaline phosphatase & urinary hydroxyproline
  • Differing radiographic appearance
1.

One family has been reported to date [Evans et al 2012].

Bacterial infections and tubercular osteomyelitis may show some resemblance clinically and radiologically.

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with multicentric osteolysis nodulosis and arthropathy (MONA), the following evaluations are recommended:

  • Complete skeletal survey
  • Evaluation by an orthopedic surgeon, rheumatologist, and physical therapist to assess joint range of motion
  • Cardiac evaluation, including echocardiogram
  • Eye examination
  • Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Treatment is supportive.

Osteopenia and osteolysis

Joints

  • Physical therapy may slow the rate of development of contractures and prolong mobility.
  • Surgical release of contractures may not help [Author, personal observation].
  • Aids to ensure mobility (wheelchair and walking aids) may be needed as the disease progresses.
  • Nonsteroidal anti-inflammatory drugs may not provide sufficient relief. Referral to a rheumatologist or pain clinic may be beneficial to develop an individual pain management plan.

Cardiac manifestations. Provide medical or surgical interventions as appropriate.

Surveillance

The following are appropriate:

  • Annual assessment of joints by a rheumatologist or orthopedic surgeon
  • Follow up of congenital heart defects as per the treating cardiologist

Agents/Circumstances to Avoid

Avoid physical trauma to reduce the risk of fractures.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

No information on pregnancy management and outcomes is available.

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Multicentric osteolysis nodulosis and arthropathy (MONA) is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

  • The parents of an affected child are obligate heterozygotes (i.e., carriers of one MMP2 pathogenic variant).
  • Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Offspring of a proband. The offspring of an individual with MONA are obligate heterozygotes (carriers) for a pathogenic variant in MMP2.

Other family members. Each sib of the proband's parents is at a 50% risk of being a carrier of an MMP2 pathogenic variant.

Carrier (Heterozygote) Detection

Carrier testing for at-risk relatives requires prior identification of the MMP2 pathogenic variants in the family.

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Diagnosis

Once the MMP2 pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Multicentric Osteolysis Nodulosis and Arthropathy: Genes and Databases

GeneChromosome LocusProteinLocus-Specific DatabasesHGMDClinVar
MMP216q12​.272 kDa type IV collagenaseMMP2 databaseMMP2MMP2

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Multicentric Osteolysis Nodulosis and Arthropathy (View All in OMIM)

120360MATRIX METALLOPROTEINASE 2; MMP2
259600MULTICENTRIC OSTEOLYSIS, NODULOSIS, AND ARTHROPATHY; MONA

Molecular Pathogenesis

Gene structure. The clinically relevant transcript, NM_004530.5, spans 3558 bp and has 13 exons; it is the longest transcript. Alternative splicing may give rise to as many as eight different transcripts. See Table A, Gene for a detailed summary of gene and protein information.

Pathogenic variants. To date, 22 MMP2 variants have been reported in affected individuals from 27 families [Martignetti et al 2001, Zankl et al 2005, Rouzier et al 2006, Phadke et al 2007, Zankl et al 2007, Tuysuz et al 2009, Gok et al 2010, Jeong et al 2010, Temtamy et al 2012, Castberg et al 2013, Azzollini et al 2014, Ekbote et al 2014, Bader-Meunier et al 2016, Bhavani et al 2016] (see Table A, Locus Specific and HGMD). Pathogenic variants include deletions and missense, nonsense, and splice site variants. Most pathogenic variants are private and homozygous.

Normal gene product. MMP2 encodes MMP2, the 72-kd type IV collagenase protein composed of 660 amino acids, also known as gelatinase or metalloproteinase-2 enzyme. MMP2 consists of four functional domains: signal peptide, propeptide domain, catalytic domain, and hemopexin domain.

Abnormal gene product. Most MMP2 pathogenic variants lead to loss of gelatinolytic activity of the enzyme MMP2 [Azzollini et al 2014].

The study of osteoblast cell lines from Mmp2-null mice showed that the loss of Mmp2 protein leads to decreased bone mineralization, destruction of articular cartilage, joint erosion, and defects in osteoblast and osteoclast growth [Mosig et al 2007].

Cancer and Benign Tumors

Somatic MMP2 pathogenic variants that result in abnormal MMP2 expression are associated with cancers (e.g., gastric, colorectal, ovarian, melanoma, breast, and lung cancers). The COSMIC (Catalogue of Somatic Mutations in Cancer) database shows 192 unique MMP2 variants in tissues associated with cancers.

References

Literature Cited

  • Al-Mayouf SM, Majeed M, Hugosson C, Bahabri S. New form of idiopathic osteolysis: nodulosis, arthropathy and osteolysis (NAO) syndrome. Am J Med Genet. 2000;93:5–10. [PubMed: 10861675]
  • Azzollini J, Rovina D, Gervasini C, Parenti I, Fratoni A, Cubellis MV, Cerri A, Pietrogrande L, Larizza L. Functional characterisation of a novel mutation affecting the catalytic domain of MMP2 in siblings with multicentric osteolysis, nodulosis and arthropathy. J Hum Genet. 2014;59:631–7. [PubMed: 25273674]
  • Bader-Meunier B, Bonafé L, Fraitag S, Breton S, Bodemer C, Baujat G. Mutation in MMP2 gene may result in scleroderma-like skin thickening. Ann Rheum Dis. 2016;75:e1. [PubMed: 26420579]
  • Bhavani GS, Shah H, Shukla A, Gupta N, Gowrishankar K, Rao AP, Kabra M, Agarwal M, Ranganath P, Ekbote AV, Phadke SR, Kamath A, Dalal A, Girisha KM. Clinical and mutation profile of multicentric osteolysis nodulosis and arthropathy. Am J Med Genet A. 2016;170A:410–7. [PubMed: 26601801]
  • Castberg FC, Kjaergaard S, Mosig RA, Lobl M, Martignetti C, Martignetti JA, Myrup C, Zak M. Multicentric osteolysis with nodulosis and arthropathy (MONA) with cardiac malformation, mimicking polyarticular juvenile idiopathic arthritis: case report and literature review. Eur J Pediatr. 2013;172:1657–63. [PubMed: 23900523]
  • Ekbote AV, Danda S, Zankl A, Mandal K, Maguire T, Ungerer K. Patient with mutation in the matrix metalloproteinase 2 (MMP2) gene - a case report and review of the literature. J Clin Res Pediatr Endocrinol. 2014;6:40–6. [PMC free article: PMC3986738] [PubMed: 24637309]
  • Evans BR, Mosig RA, Lobl M, Martignetti CR, Camacho C, Grum-Tokars V, Glucksman MJ, Martignetti JA. Mutation of membrane type-1 metalloproteinase, MT1-MMP, causes the multicentric osteolysis and arthritis disease Winchester syndrome. Am J Hum Genet. 2012;91:572–6. [PMC free article: PMC3512002] [PubMed: 22922033]
  • Gok F, Crettol LM, Alanay Y, Hacihamdioglu B, Kocaoglu M, Bonafe L, Ozen S. Clinical and radiographic findings in two brothers affected with a novel mutation in matrix metalloproteinase 2 gene. Eur J Pediatr. 2010;169:363–7. [PubMed: 19653001]
  • Jeong SY, Kim BY, Kim HJ, Yang JA, Kim OH. A novel homozygous MMP2 mutation in a patient with Torg-Winchester syndrome. J Hum Genet. 2010;55:764–6. [PubMed: 20720557]
  • Martignetti JA, Aqeel AA, Sewairi WA, Boumah CE, Kambouris M, Mayouf SA, Sheth KV, Eid WA, Dowling O, Harris J, Glucksman MJ, Bahabri S, Meyer BF, Desnick RJ. Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome. Nat Genet. 2001;28:261–5. [PubMed: 11431697]
  • Mosig RA, Dowling O, DiFeo A, Ramirez MC, Parker IC, Abe E, Diouri J, Aqeel AA, Wylie JD, Oblander SA, Madri J, Bianco P, Apte SS, Zaidi M, Doty SB, Majeska RJ, Schaffler MB, Martignetti JA. Loss of MMP-2 disrupts skeletal and craniofacial development and results in decreased bone mineralization, joint erosion and defects in osteoblast and osteoclast growth. Hum Mol Genet. 2007;16:1113–23. [PMC free article: PMC2576517] [PubMed: 17400654]
  • Phadke SR, Ramirez M, Difeo A, Martignetti JA, Girisha KM. Torg-Winchester syndrome: lack of efficacy of pamidronate therapy. Clin Dysmorphol. 2007;16:95–100. [PubMed: 17351352]
  • Rouzier C, Vanatka R, Bannwarth S, Philip N, Coussement A, Paquis-Flucklinger V, Lambert JC. A novel homozygous MMP2 mutation in a family with Winchester syndrome. Clin Genet. 2006;69:271–6. [PubMed: 16542393]
  • Temtamy SA, Ismail S, Aglan MS, Ashour AM, Hosny LA, El-Badry TH, Aboul-Ezz EH, Amr K, Fateen E, Maguire T, Ungerer K, Zankl A. A report of three patients with MMP2 associated hereditary osteolysis. Genet Couns. 2012;23:175–84. [PubMed: 22876575]
  • Tuysuz B, Mosig R, Altun G, Sancak S, Glucksman MJ, Martignetti JA. A novel matrix metalloproteinase 2 (MMP2) terminal hemopexin domain mutation in a family with multicentric osteolysis with nodulosis and arthritis with cardiac defects. Eur J Hum Genet. 2009;17:565–72. [PMC free article: PMC2721823] [PubMed: 18985071]
  • Zankl A, Bonafé L, Calcaterra V, Di Rocco M, Superti-Furga A. Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2. Clin Genet. 2005;67:261–6. [PubMed: 15691365]
  • Zankl A, Pachman L, Poznanski A, Bonafé L, Wang F, Shusterman Y, Fishman DA, Superti-Furga A. Torg syndrome is caused by inactivating mutations in MMP2 and is allelic to NAO and Winchester syndrome. J Bone Miner Res. 2007;22:329–33. [PubMed: 17059372]

Chapter Notes

Acknowledgments

  • Indian Council of Medical Research – Clinical and molecular evaluation of inherited arthropathies and multiple vertebral segmentation defects (BMS 54/2/2013)
  • Department of Science and Technology – Application of autozygosity mapping and exome sequencing to identify genetic basis of disorders of skeletal development (SB/SO/HS/005/2014)

Revision History

  • 14 July 2016 (bp) Review posted live
  • 22 February 2016 (kmg) Original submission
Copyright © 1993-2020, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2020 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

Bookshelf ID: NBK373578PMID: 27413800

Views

Tests in GTR by Gene

Related information

  • OMIM
    Related OMIM records
  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed
  • Gene
    Locus Links

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...