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Multiple Epiphyseal Dysplasia, Dominant

MedGen UID:
433160
•Concept ID:
CN043640
•
Disease or Syndrome
Gene (location): MATN3 (2p24.1)
Related genes: COMP, COL9A3, COL9A2, COL9A1

Disease characteristics

Excerpted from the GeneReview: Multiple Epiphyseal Dysplasia, Autosomal Dominant
Autosomal dominant multiple epiphyseal dysplasia (MED) presents in early childhood, usually with pain in the hips and/or knees after exercise. Affected children report fatigue with long-distance walking. Waddling gait may be present. Adult height is either in the lower range of normal or mildly shortened. The limbs are relatively short in comparison to the trunk. Pain and joint deformity progress, resulting in early-onset osteoarthritis, particularly of the large weight-bearing joints. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Michael D Briggs  |  Michael J Wright  |  Geert R Mortier   view full author information

Professional guidelines

PubMed

Genotype to phenotype correlations in cartilage oligomeric matrix protein associated chondrodysplasias.
Briggs MD, Brock J, Ramsden SC, Bell PA
Eur J Hum Genet 2014 Nov;22(11):1278-82. Epub 2014 Mar 5 doi: 10.1038/ejhg.2014.30. PMID: 24595329Free PMC Article

Recent clinical studies

Etiology

Dominant Stickler Syndrome.
Soh Z, Richards AJ, McNinch A, Alexander P, Martin H, Snead MP
Genes (Basel) 2022 Jun 18;13(6) doi: 10.3390/genes13061089. PMID: 35741851Free PMC Article
Osteogenesis imperfecta.
Forlino A, Marini JC
Lancet 2016 Apr 16;387(10028):1657-71. Epub 2015 Nov 3 doi: 10.1016/S0140-6736(15)00728-X. PMID: 26542481Free PMC Article
Classification of osteogenesis imperfecta.
Fratzl-Zelman N, Misof BM, Roschger P, Klaushofer K
Wien Med Wochenschr 2015 Jul;165(13-14):264-70. Epub 2015 Jul 25 doi: 10.1007/s10354-015-0368-3. PMID: 26208476
An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes.
Wheway G, Schmidts M, Mans DA, Szymanska K, Nguyen TT, Racher H, Phelps IG, Toedt G, Kennedy J, Wunderlich KA, Sorusch N, Abdelhamed ZA, Natarajan S, Herridge W, van Reeuwijk J, Horn N, Boldt K, Parry DA, Letteboer SJF, Roosing S, Adams M, Bell SM, Bond J, Higgins J, Morrison EE, Tomlinson DC, Slaats GG, van Dam TJP, Huang L, Kessler K, Giessl A, Logan CV, Boyle EA, Shendure J, Anazi S, Aldahmesh M, Al Hazzaa S, Hegele RA, Ober C, Frosk P, Mhanni AA, Chodirker BN, Chudley AE, Lamont R, Bernier FP, Beaulieu CL, Gordon P, Pon RT, Donahue C, Barkovich AJ, Wolf L, Toomes C, Thiel CT, Boycott KM, McKibbin M, Inglehearn CF; UK10K Consortium; University of Washington Center for Mendelian Genomics, Stewart F, Omran H, Huynen MA, Sergouniotis PI, Alkuraya FS, Parboosingh JS, Innes AM, Willoughby CE, Giles RH, Webster AR, Ueffing M, Blacque O, Gleeson JG, Wolfrum U, Beales PL, Gibson T, Doherty D, Mitchison HM, Roepman R, Johnson CA
Nat Cell Biol 2015 Aug;17(8):1074-1087. Epub 2015 Jul 13 doi: 10.1038/ncb3201. PMID: 26167768Free PMC Article
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

Osteogenesis imperfecta: diagnosis and treatment.
Palomo T, Vilaça T, Lazaretti-Castro M
Curr Opin Endocrinol Diabetes Obes 2017 Dec;24(6):381-388. doi: 10.1097/MED.0000000000000367. PMID: 28863000
Osteogenesis imperfecta.
Marini JC, Forlino A, Bächinger HP, Bishop NJ, Byers PH, Paepe A, Fassier F, Fratzl-Zelman N, Kozloff KM, Krakow D, Montpetit K, Semler O
Nat Rev Dis Primers 2017 Aug 18;3:17052. doi: 10.1038/nrdp.2017.52. PMID: 28820180
Osteogenesis imperfecta.
Forlino A, Marini JC
Lancet 2016 Apr 16;387(10028):1657-71. Epub 2015 Nov 3 doi: 10.1016/S0140-6736(15)00728-X. PMID: 26542481Free PMC Article
Multiple epiphyseal dysplasia.
Anthony S, Munk R, Skakun W, Masini M
J Am Acad Orthop Surg 2015 Mar;23(3):164-72. Epub 2015 Feb 9 doi: 10.5435/JAAOS-D-13-00173. PMID: 25667404
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

Therapy

Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients.
Maioli M, Gnoli M, Boarini M, Tremosini M, Zambrano A, Pedrini E, Mordenti M, Corsini S, D'Eufemia P, Versacci P, Celli M, Sangiorgi L
Eur J Hum Genet 2019 Jul;27(7):1090-1100. Epub 2019 Mar 18 doi: 10.1038/s41431-019-0373-x. PMID: 30886339Free PMC Article
Camurati-Engelmann Disease.
Van Hul W, Boudin E, Vanhoenacker FM, Mortier G
Calcif Tissue Int 2019 May;104(5):554-560. Epub 2019 Feb 5 doi: 10.1007/s00223-019-00532-1. PMID: 30721323
Osteogenesis imperfecta: diagnosis and treatment.
Palomo T, Vilaça T, Lazaretti-Castro M
Curr Opin Endocrinol Diabetes Obes 2017 Dec;24(6):381-388. doi: 10.1097/MED.0000000000000367. PMID: 28863000
Osteogenesis imperfecta.
Forlino A, Marini JC
Lancet 2016 Apr 16;387(10028):1657-71. Epub 2015 Nov 3 doi: 10.1016/S0140-6736(15)00728-X. PMID: 26542481Free PMC Article
Primary osteoporosis.
Bishop N
Endocr Dev 2009;16:157-69. Epub 2009 Jun 3 doi: 10.1159/000223694. PMID: 19494666

Prognosis

Dominant negative variants in KIF5B cause osteogenesis imperfecta via down regulation of mTOR signaling.
Marom R, Zhang B, Washington ME, Song IW, Burrage LC, Rossi VC, Berrier AS, Lindsey A, Lesinski J, Nonet ML, Chen J, Baldridge D, Silverman GA, Sutton VR, Rosenfeld JA, Tran AA, Hicks MJ, Murdock DR, Dai H, Weis M, Jhangiani SN, Muzny DM, Gibbs RA, Caswell R, Pottinger C, Cilliers D, Stals K; Undiagnosed Diseases Network, Eyre D, Krakow D, Schedl T, Pak SC, Lee BH
PLoS Genet 2023 Nov;19(11):e1011005. Epub 2023 Nov 7 doi: 10.1371/journal.pgen.1011005. PMID: 37934770Free PMC Article
Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients.
Maioli M, Gnoli M, Boarini M, Tremosini M, Zambrano A, Pedrini E, Mordenti M, Corsini S, D'Eufemia P, Versacci P, Celli M, Sangiorgi L
Eur J Hum Genet 2019 Jul;27(7):1090-1100. Epub 2019 Mar 18 doi: 10.1038/s41431-019-0373-x. PMID: 30886339Free PMC Article
Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA.
Zhang J, Li J, Saucier JB, Feng Y, Jiang Y, Sinson J, McCombs AK, Schmitt ES, Peacock S, Chen S, Dai H, Ge X, Wang G, Shaw CA, Mei H, Breman A, Xia F, Yang Y, Purgason A, Pourpak A, Chen Z, Wang X, Wang Y, Kulkarni S, Choy KW, Wapner RJ, Van den Veyver IB, Beaudet A, Parmar S, Wong LJ, Eng CM
Nat Med 2019 Mar;25(3):439-447. Epub 2019 Jan 28 doi: 10.1038/s41591-018-0334-x. PMID: 30692697
Multiple osteochondromas.
Bovée JV
Orphanet J Rare Dis 2008 Feb 13;3:3. doi: 10.1186/1750-1172-3-3. PMID: 18271966Free PMC Article
Gonadotrophin receptors.
Clayton RN
Baillieres Clin Endocrinol Metab 1996 Jan;10(1):1-8. doi: 10.1016/s0950-351x(96)80250-3. PMID: 8734448

Clinical prediction guides

Dominant negative variants in KIF5B cause osteogenesis imperfecta via down regulation of mTOR signaling.
Marom R, Zhang B, Washington ME, Song IW, Burrage LC, Rossi VC, Berrier AS, Lindsey A, Lesinski J, Nonet ML, Chen J, Baldridge D, Silverman GA, Sutton VR, Rosenfeld JA, Tran AA, Hicks MJ, Murdock DR, Dai H, Weis M, Jhangiani SN, Muzny DM, Gibbs RA, Caswell R, Pottinger C, Cilliers D, Stals K; Undiagnosed Diseases Network, Eyre D, Krakow D, Schedl T, Pak SC, Lee BH
PLoS Genet 2023 Nov;19(11):e1011005. Epub 2023 Nov 7 doi: 10.1371/journal.pgen.1011005. PMID: 37934770Free PMC Article
FZD2 regulates limb development by mediating β-catenin-dependent and -independent Wnt signaling pathways.
Zhu X, Xu M, Leu NA, Morrisey EE, Millar SE
Dis Model Mech 2023 Mar 1;16(3) Epub 2023 Mar 24 doi: 10.1242/dmm.049876. PMID: 36867021Free PMC Article
Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients.
Maioli M, Gnoli M, Boarini M, Tremosini M, Zambrano A, Pedrini E, Mordenti M, Corsini S, D'Eufemia P, Versacci P, Celli M, Sangiorgi L
Eur J Hum Genet 2019 Jul;27(7):1090-1100. Epub 2019 Mar 18 doi: 10.1038/s41431-019-0373-x. PMID: 30886339Free PMC Article
Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA.
Zhang J, Li J, Saucier JB, Feng Y, Jiang Y, Sinson J, McCombs AK, Schmitt ES, Peacock S, Chen S, Dai H, Ge X, Wang G, Shaw CA, Mei H, Breman A, Xia F, Yang Y, Purgason A, Pourpak A, Chen Z, Wang X, Wang Y, Kulkarni S, Choy KW, Wapner RJ, Van den Veyver IB, Beaudet A, Parmar S, Wong LJ, Eng CM
Nat Med 2019 Mar;25(3):439-447. Epub 2019 Jan 28 doi: 10.1038/s41591-018-0334-x. PMID: 30692697
An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes.
Wheway G, Schmidts M, Mans DA, Szymanska K, Nguyen TT, Racher H, Phelps IG, Toedt G, Kennedy J, Wunderlich KA, Sorusch N, Abdelhamed ZA, Natarajan S, Herridge W, van Reeuwijk J, Horn N, Boldt K, Parry DA, Letteboer SJF, Roosing S, Adams M, Bell SM, Bond J, Higgins J, Morrison EE, Tomlinson DC, Slaats GG, van Dam TJP, Huang L, Kessler K, Giessl A, Logan CV, Boyle EA, Shendure J, Anazi S, Aldahmesh M, Al Hazzaa S, Hegele RA, Ober C, Frosk P, Mhanni AA, Chodirker BN, Chudley AE, Lamont R, Bernier FP, Beaulieu CL, Gordon P, Pon RT, Donahue C, Barkovich AJ, Wolf L, Toomes C, Thiel CT, Boycott KM, McKibbin M, Inglehearn CF; UK10K Consortium; University of Washington Center for Mendelian Genomics, Stewart F, Omran H, Huynen MA, Sergouniotis PI, Alkuraya FS, Parboosingh JS, Innes AM, Willoughby CE, Giles RH, Webster AR, Ueffing M, Blacque O, Gleeson JG, Wolfrum U, Beales PL, Gibson T, Doherty D, Mitchison HM, Roepman R, Johnson CA
Nat Cell Biol 2015 Aug;17(8):1074-1087. Epub 2015 Jul 13 doi: 10.1038/ncb3201. PMID: 26167768Free PMC Article

Recent systematic reviews

Trichorhinophalangeal Syndrome Orthopaedic Manifestations and Management: A Systematic Review.
Ellison E, Grampp SJ, Ellison S, Seeley A, Seeley M
J Am Acad Orthop Surg Glob Res Rev 2024 Aug 1;8(8) Epub 2024 Aug 19 doi: 10.5435/JAAOSGlobal-D-24-00010. PMID: 39162698Free PMC Article
Meta-analysis of Association Studies of Selenoprotein Gene Polymorphism and Kashin-Beck Disease: an Updated Systematic Review.
Yu FF, Sun L, Zhou GY, Ping ZG, Guo X, Ba Y
Biol Trace Elem Res 2022 Feb;200(2):543-550. Epub 2021 Apr 12 doi: 10.1007/s12011-021-02705-2. PMID: 33844169
GDF5 mutation case report and a systematic review of molecular and clinical spectrum: Expanding current knowledge on genotype-phenotype correlations.
Genovesi ML, Guadagnolo D, Marchionni E, Giovannetti A, Traversa A, Panzironi N, Bernardo S, Palumbo P, Petrizzelli F, Carella M, Mazza T, Pizzuti A, Caputo V
Bone 2021 Mar;144:115803. Epub 2021 Jan 12 doi: 10.1016/j.bone.2020.115803. PMID: 33333243
Earlier detection of hypochondroplasia: A large single-center UK case series and systematic review.
Sabir AH, Sheikh J, Singh A, Morley E, Cocca A, Cheung MS, Irving M
Am J Med Genet A 2021 Jan;185(1):73-82. Epub 2020 Oct 14 doi: 10.1002/ajmg.a.61912. PMID: 33051983
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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