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Epiphyseal dysplasia, multiple, 3(EDM3)

MedGen UID:
322091
Concept ID:
C1832998
Disease or Syndrome
Synonyms: COL9A3-Related Multiple Epiphyseal Dysplasia; EDM3; Epiphyseal dysplasia, multiple, 3, with or without myopathy
 
Gene (location): COL9A3 (20q13.33)
 
Monarch Initiative: MONDO:0010964
OMIM®: 600969

Disease characteristics

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]
Authors:
Michael D Briggs  |  Michael J Wright  |  Geert R Mortier   view full author information

Additional descriptions

From OMIM
Multiple epiphyseal dysplasia is characterized by early-onset short stature, waddling gait, and stiffness and/or pain in the knees and sometimes other joints (Muragaki et al., 1996). For a general phenotypic description and a discussion of genetic heterogeneity of multiple epiphyseal dysplasia, see EDM1 (132400).  http://www.omim.org/entry/600969
From MedlinePlus Genetics
Multiple epiphyseal dysplasia is a disorder of cartilage and bone development primarily affecting the ends of the long bones in the arms and legs (epiphyses). There are two types of multiple epiphyseal dysplasia, which can be distinguished by their pattern of inheritance. Both the dominant and recessive types have relatively mild signs and symptoms, including joint pain that most commonly affects the hips and knees, early-onset arthritis, and a waddling walk. Although some people with multiple epiphyseal dysplasia have mild short stature as adults, most are of normal height. The majority of individuals are diagnosed during childhood; however, some mild cases may not be diagnosed until adulthood.

Recessive multiple epiphyseal dysplasia is distinguished from the dominant type by malformations of the hands, feet, and knees and abnormal curvature of the spine (scoliosis). About 50 percent of individuals with recessive multiple epiphyseal dysplasia are born with at least one abnormal feature, including an inward- and upward-turning foot (clubfoot), an opening in the roof of the mouth (cleft palate), an unusual curving of the fingers or toes (clinodactyly), or ear swelling. An abnormality of the kneecap called a double-layered patella is also relatively common.  https://medlineplus.gov/genetics/condition/multiple-epiphyseal-dysplasia

Clinical features

From HPO
Knee pain
MedGen UID:
65421
Concept ID:
C0231749
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the knee.
Short metacarpal
MedGen UID:
323064
Concept ID:
C1837084
Anatomical Abnormality
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
Limited knee extension
MedGen UID:
336755
Concept ID:
C1844690
Finding
Reduced ability to extend (straighten) the knee joint.
Limited elbow extension
MedGen UID:
401158
Concept ID:
C1867103
Finding
Limited ability to straighten the arm at the elbow joint.
Abnormal hip joint morphology
MedGen UID:
866552
Concept ID:
C4020870
Anatomical Abnormality
An abnormality of the hip joint.
Mild short stature
MedGen UID:
461427
Concept ID:
C3150077
Finding
A mild degree of short stature, more than -2 SD but not more than -3 SD from mean corrected for age and sex.
Osteoarthritis
MedGen UID:
45244
Concept ID:
C0029408
Disease or Syndrome
Osteoarthritis (OA) is a degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis (Meulenbelt et al., 2006). Clinical problems include pain and joint stiffness often leading to significant disability and joint replacement. Osteoarthritis exhibits a clear predilection for specific joints; it appears most commonly in the hip and knee joints and lumbar and cervical spine, as well as in the distal interphalangeal and the first carpometacarpal (base of thumb) and proximal interphalangeal joints of the hand; however, patients with osteoarthritis may have 1, a few, or all of these sites affected (Stefansson et al., 2003). According to a conservative estimate, greater than 70% of the population of the United States at age 65 years is affected by the disease, reflecting its age dependence. Genetic Heterogeneity of Susceptibility to Osteoarthritis Susceptibility to osteoarthritis has been associated with variation in other genes: OS2 (140600) with variation in the MATN3 gene (602109) on chromosome 2p24; OS3 (607850) with variation in the ASPN gene (608135) on chromosome 9q22; and OS5 (612400) with variation in the GDF5 gene (601146) on chromosome 20q11. Other susceptibility loci for osteoarthritis have been mapped to chromosomes 2q33 (OS4; 610839) and 3p24 (OS6; 612401).
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Epiphyseal dysplasia
MedGen UID:
95932
Concept ID:
C0392476
Congenital Abnormality
Irregular epiphyses
MedGen UID:
337584
Concept ID:
C1846449
Finding
An alteration of the normally smooth contour of the epiphysis leading to an irregular appearance.
Small epiphyses
MedGen UID:
339612
Concept ID:
C1846803
Finding
Reduction in the size or volume of epiphyses.
Delayed epiphyseal ossification
MedGen UID:
351324
Concept ID:
C1865200
Finding
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Mildly elevated creatine kinase
MedGen UID:
342469
Concept ID:
C1850309
Finding

Professional guidelines

PubMed

Yang J, Serino J, Olsen AS, Berger RA, Della Valle CJ
Knee 2021 Jun;30:106-112. Epub 2021 Apr 20 doi: 10.1016/j.knee.2021.03.019. PMID: 33887621
Briggs MD, Chapman KL
Hum Mutat 2002 May;19(5):465-78. doi: 10.1002/humu.10066. PMID: 11968079

Recent clinical studies

Etiology

Markova T, Kenis V, Melchenko E, Alieva A, Nagornova T, Orlova A, Ogorodova N, Shchagina O, Polyakov A, Dadali E, Kutsev S
Genes (Basel) 2022 Aug 24;13(9) doi: 10.3390/genes13091512. PMID: 36140680Free PMC Article
Vanlommel J, Vanlommel L, Molenaers B, Simon JP
Orthop Traumatol Surg Res 2018 May;104(3):301-305. Epub 2017 Dec 21 doi: 10.1016/j.otsr.2017.11.014. PMID: 29274861
Park KW, Kim JH, Sung S, Lee MY, Song HR
J Pediatr Orthop 2014 Oct-Nov;34(7):738-42. doi: 10.1097/BPO.0000000000000172. PMID: 25210941
Dahlqvist J, Orlén H, Matsson H, Dahl N, Lönnerholm T, Gustavson KH
Acta Orthop 2009 Dec;80(6):711-5. doi: 10.3109/17453670903473032. PMID: 19995321Free PMC Article
Lachman RS, Krakow D, Cohn DH, Rimoin DL
Pediatr Radiol 2005 Feb;35(2):116-23. Epub 2004 Oct 21 doi: 10.1007/s00247-004-1323-4. PMID: 15503005

Diagnosis

Markova T, Kenis V, Melchenko E, Alieva A, Nagornova T, Orlova A, Ogorodova N, Shchagina O, Polyakov A, Dadali E, Kutsev S
Genes (Basel) 2022 Aug 24;13(9) doi: 10.3390/genes13091512. PMID: 36140680Free PMC Article
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
Juneja A, Sultan A, Bhatnagar S
J Indian Soc Pedod Prev Dent 2012 Jul-Sep;30(3):250-3. doi: 10.4103/0970-4388.105019. PMID: 23263430
Dahlqvist J, Orlén H, Matsson H, Dahl N, Lönnerholm T, Gustavson KH
Acta Orthop 2009 Dec;80(6):711-5. doi: 10.3109/17453670903473032. PMID: 19995321Free PMC Article
Briggs MD, Chapman KL
Hum Mutat 2002 May;19(5):465-78. doi: 10.1002/humu.10066. PMID: 11968079

Therapy

Chang YY, Lee CC, Lin SC, Kuo KN, Chang JF, Wu KW, Wang TM
Orphanet J Rare Dis 2023 Oct 30;18(1):340. doi: 10.1186/s13023-023-02920-1. PMID: 37904148Free PMC Article
Yang J, Serino J, Olsen AS, Berger RA, Della Valle CJ
Knee 2021 Jun;30:106-112. Epub 2021 Apr 20 doi: 10.1016/j.knee.2021.03.019. PMID: 33887621
Raggio CL, Yonko EA, Khan SI, Carter EM, Citron KP, Bostrom MPG, Figgie MP
J Arthroplasty 2020 Aug;35(8):1993-2001. Epub 2020 Apr 9 doi: 10.1016/j.arth.2020.04.007. PMID: 32386881
Patel H, Cichos KH, Moon AS, McGwin G Jr, Ponce BA, Ghanem ES
Orthop Traumatol Surg Res 2019 Nov;105(7):1297-1301. Epub 2019 Sep 18 doi: 10.1016/j.otsr.2019.06.013. PMID: 31542311
Uçar A, Aydemir Y, Doğan A, Tunçez E
Diabet Med 2016 Mar;33(3):e13-6. doi: 10.1111/dme.12968. PMID: 26433138

Prognosis

Hung TY, Wu KW, Lee CC, Lin SC, Kuo KN, Wang TM
J Pediatr Orthop 2023 Jan 1;43(1):e67-e73. Epub 2022 Nov 2 doi: 10.1097/BPO.0000000000002296. PMID: 36509457
Yang J, Serino J, Olsen AS, Berger RA, Della Valle CJ
Knee 2021 Jun;30:106-112. Epub 2021 Apr 20 doi: 10.1016/j.knee.2021.03.019. PMID: 33887621
Vanlommel J, Vanlommel L, Molenaers B, Simon JP
Orthop Traumatol Surg Res 2018 May;104(3):301-305. Epub 2017 Dec 21 doi: 10.1016/j.otsr.2017.11.014. PMID: 29274861
Park KW, Kim JH, Sung S, Lee MY, Song HR
J Pediatr Orthop 2014 Oct-Nov;34(7):738-42. doi: 10.1097/BPO.0000000000000172. PMID: 25210941
Lachman RS, Krakow D, Cohn DH, Rimoin DL
Pediatr Radiol 2005 Feb;35(2):116-23. Epub 2004 Oct 21 doi: 10.1007/s00247-004-1323-4. PMID: 15503005

Clinical prediction guides

Chang YY, Lee CC, Lin SC, Kuo KN, Chang JF, Wu KW, Wang TM
Orphanet J Rare Dis 2023 Oct 30;18(1):340. doi: 10.1186/s13023-023-02920-1. PMID: 37904148Free PMC Article
Markova T, Kenis V, Melchenko E, Alieva A, Nagornova T, Orlova A, Ogorodova N, Shchagina O, Polyakov A, Dadali E, Kutsev S
Genes (Basel) 2022 Aug 24;13(9) doi: 10.3390/genes13091512. PMID: 36140680Free PMC Article
Liang H, Hou Y, Pang Q, Jiang Y, Wang O, Li M, Xing X, Zhu H, Xia W
Calcif Tissue Int 2022 Mar;110(3):313-323. Epub 2021 Oct 28 doi: 10.1007/s00223-021-00920-6. PMID: 34709441
Vanlommel J, Vanlommel L, Molenaers B, Simon JP
Orthop Traumatol Surg Res 2018 May;104(3):301-305. Epub 2017 Dec 21 doi: 10.1016/j.otsr.2017.11.014. PMID: 29274861
Park KW, Kim JH, Sung S, Lee MY, Song HR
J Pediatr Orthop 2014 Oct-Nov;34(7):738-42. doi: 10.1097/BPO.0000000000000172. PMID: 25210941

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