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Multiple epiphyseal dysplasia 4(EDM4)

MedGen UID:
376164
Concept ID:
C1847593
Disease or Syndrome
Synonyms: EDM4; Multiple epiphyseal dysplasia with bilayered patellae; Multiple epiphyseal dysplasia with clubfoot; Multiple epiphyseal dysplasia with double-layered patella; Multiple epiphyseal dysplasia, autosomal recessive; Multiple Epiphyseal Dysplasia, Recessive
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Multiple epiphyseal dysplasia type 4 (715672007); Autosomal recessive multiple epiphyseal dysplasia (715672007)
 
Gene (location): SLC26A2 (5q32)
OMIM®: 226900
Orphanet: ORPHA93307

Definition

Recessive multiple epiphyseal dysplasia (EDM4/rMED) is characterized by joint pain (usually in the hips or knees); malformations of hands, feet, and knees; and scoliosis. Approximately 50% of affected individuals have an abnormal finding at birth, e.g., clubfoot, clinodactyly, or (rarely) cystic ear swelling. Onset of articular pain is variable but usually occurs in late childhood. Stature is usually within the normal range prior to puberty; in adulthood, stature is only slightly diminished and ranges from 150 to 180 cm. Functional disability is mild. [from GTR]

Additional descriptions

From GeneReviews
Recessive multiple epiphyseal dysplasia (EDM4/rMED) is characterized by joint pain (usually in the hips or knees); malformations of hands, feet, and knees; and scoliosis. Approximately 50% of affected individuals have an abnormal finding at birth, e.g., clubfoot, clinodactyly, or (rarely) cystic ear swelling. Onset of articular pain is variable but usually occurs in late childhood. Stature is usually within the normal range prior to puberty; in adulthood, stature is only slightly diminished and ranges from 150 to 180 cm. Functional disability is mild.  https://www.ncbi.nlm.nih.gov/books/NBK1306
From GHR
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://ghr.nlm.nih.gov/condition/multiple-epiphyseal-dysplasia

Clinical features

Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Talipes equinovarus
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Congenital anomaly of abnormally short fingers or toes.
Short metacarpal
MedGen UID:
323064
Concept ID:
C1837084
Finding
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
Flat capital femoral epiphysis
MedGen UID:
334001
Concept ID:
C1842155
Finding
An abnormal flattening of the proximal epiphysis of the femur.
Hypoplasia of the femoral head
MedGen UID:
384014
Concept ID:
C1856920
Finding
Underdevelopment of the femoral head.
Limited elbow flexion
MedGen UID:
384015
Concept ID:
C1856922
Finding
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to \
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Dysplasia of acetabulum
MedGen UID:
9258
Concept ID:
C0019555
Congenital Abnormality
A spectrum of hip abnormalities commonly presenting in infancy involving the relationship between the femoral head and the acetabulum and that includes subluxation or dislocation at rest or upon provocation.
Multiple epiphyseal dysplasia
MedGen UID:
6461
Concept ID:
C0026760
Congenital Abnormality
Scoliosis
MedGen UID:
21278
Concept ID:
C0037932
Finding
Deformities of the SPINE characterized by abnormal bending or flexure in the vertebral column. They may be bending forward (KYPHOSIS), backward (LORDOSIS), or sideway (SCOLIOSIS).
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Congenital anomaly of abnormally short fingers or toes.
Epiphyseal dysplasia
MedGen UID:
95932
Concept ID:
C0392476
Congenital Abnormality
Short metacarpal
MedGen UID:
323064
Concept ID:
C1837084
Finding
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
Flat capital femoral epiphysis
MedGen UID:
334001
Concept ID:
C1842155
Finding
An abnormal flattening of the proximal epiphysis of the femur.
Hypoplasia of the femoral head
MedGen UID:
384014
Concept ID:
C1856920
Finding
Underdevelopment of the femoral head.
Limited elbow flexion
MedGen UID:
384015
Concept ID:
C1856922
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMultiple epiphyseal dysplasia 4
Follow this link to review classifications for Multiple epiphyseal dysplasia 4 in Orphanet.

Recent clinical studies

Etiology

Mäkitie O, Geiberger S, Horemuzova E, Hagenäs L, Moström E, Nordenskjöld M, Grigelioniene G, Nordgren A
Clin Genet 2015 Mar;87(3):273-8. Epub 2014 Apr 1 doi: 10.1111/cge.12371. PMID: 24598000
Cho TJ, Choi IH, Chung CY, Yoo WJ, Park MS, Lee DY
J Pediatr Orthop 2009 Jan-Feb;29(1):52-6. doi: 10.1097/BPO.0b013e3181901c4d. PMID: 19098647
Lim SJ, Park YS, Moon YW, Jung SM, Ha HC, Seo JG
J Arthroplasty 2009 Jan;24(1):77-82. Epub 2007 Jan 22 doi: 10.1016/j.arth.2006.01.012. PMID: 18534387
Miyake A, Nishimura G, Futami T, Ohashi H, Chiba K, Toyama Y, Furuichi T, Ikegawa S
J Hum Genet 2008;53(8):764-8. Epub 2008 Jun 14 doi: 10.1007/s10038-008-0305-z. PMID: 18553123
Bajuifer S, Letts M
Can J Surg 2005 Apr;48(2):106-9. PMID: 15887789Free PMC Article

Diagnosis

Mäkitie O, Geiberger S, Horemuzova E, Hagenäs L, Moström E, Nordenskjöld M, Grigelioniene G, Nordgren A
Clin Genet 2015 Mar;87(3):273-8. Epub 2014 Apr 1 doi: 10.1111/cge.12371. PMID: 24598000
Karaer K, Rosti RO, Torun D, Sanal HT, Guran S
Genet Couns 2012;23(4):457-63. PMID: 23431744
Taketomi S, Hiraoka H, Nakagawa T, Miyamoto Y, Kuribayashi S, Fukuda A, Takeda H, Fukai A, Hirota J, Nakajima K, Haga N, Nakamura K
J Orthop Sci 2012 Jul;17(4):507-11. Epub 2011 May 11 doi: 10.1007/s00776-011-0096-5. PMID: 21559955
Li LY, Zhao Q, Ji SJ, Zhang LJ, Li QW
Orthopedics 2011 May 18;34(5):352. doi: 10.3928/01477447-20110317-03. PMID: 21598888
Ramaswamy R, Kosashvili Y, Cameron H
J Bone Joint Surg Br 2010 Apr;92(4):489-95. doi: 10.1302/0301-620X.92B4.22897. PMID: 20357323

Therapy

Benabbad I, Rosilio M, Child CJ, Carel JC, Ross JL, Deal CL, Drop SL, Zimmermann AG, Jia N, Quigley CA, Blum WF
Horm Res Paediatr 2017;87(1):42-50. Epub 2016 Dec 22 doi: 10.1159/000452973. PMID: 28002818Free PMC Article
Fradet A, Fitzgerald J
J Hum Genet 2017 Feb;62(2):135-140. Epub 2016 Oct 6 doi: 10.1038/jhg.2016.119. PMID: 27708270Free PMC Article
Uçar A, Aydemir Y, Doğan A, Tunçez E
Diabet Med 2016 Mar;33(3):e13-6. doi: 10.1111/dme.12968. PMID: 26433138
Habeb AM, Deeb A, Johnson M, Abdullah M, Abdulrasoul M, Al-Awneh H, Al-Maghamsi MS, Al-Murshedi F, Al-Saif R, Al-Sinani S, Ramadan D, Tfayli H, Flanagan SE, Ellard S
Horm Res Paediatr 2015;83(3):190-7. Epub 2015 Feb 5 doi: 10.1159/000369804. PMID: 25659842Free PMC Article
Kaname T, Ki CS, Niikawa N, Baillie GS, Day JP, Yamamura K, Ohta T, Nishimura G, Mastuura N, Kim OH, Sohn YB, Kim HW, Cho SY, Ko AR, Lee JY, Kim HW, Ryu SH, Rhee H, Yang KS, Joo K, Lee J, Kim CH, Cho KH, Kim D, Yanagi K, Naritomi K, Yoshiura K, Kondoh T, Nii E, Tonoki H, Houslay MD, Jin DK
Cell Signal 2014 Nov;26(11):2446-59. Epub 2014 Jul 24 doi: 10.1016/j.cellsig.2014.07.025. PMID: 25064455

Prognosis

Cho TJ, Choi IH, Chung CY, Yoo WJ, Park MS, Lee DY
J Pediatr Orthop 2009 Jan-Feb;29(1):52-6. doi: 10.1097/BPO.0b013e3181901c4d. PMID: 19098647
Lim SJ, Park YS, Moon YW, Jung SM, Ha HC, Seo JG
J Arthroplasty 2009 Jan;24(1):77-82. Epub 2007 Jan 22 doi: 10.1016/j.arth.2006.01.012. PMID: 18534387
Miyake A, Nishimura G, Futami T, Ohashi H, Chiba K, Toyama Y, Furuichi T, Ikegawa S
J Hum Genet 2008;53(8):764-8. Epub 2008 Jun 14 doi: 10.1007/s10038-008-0305-z. PMID: 18553123
Bajuifer S, Letts M
Can J Surg 2005 Apr;48(2):106-9. PMID: 15887789Free PMC Article
Mostert AK, Dijkstra PF, Jansen BR, van Horn JR, de Graaf B, Heutink P, Lindhout D
Am J Med Genet A 2003 Aug 1;120A(4):490-7. doi: 10.1002/ajmg.a.20034. PMID: 12884427

Clinical prediction guides

Chotigavanichaya C, Leeprakobboon D, Eamsobhana P, Kaewpornsawan K
J Med Assoc Thai 2014 Sep;97 Suppl 9:S78-82. PMID: 25365895
Lim SJ, Park YS, Moon YW, Jung SM, Ha HC, Seo JG
J Arthroplasty 2009 Jan;24(1):77-82. Epub 2007 Jan 22 doi: 10.1016/j.arth.2006.01.012. PMID: 18534387
Miyake A, Nishimura G, Futami T, Ohashi H, Chiba K, Toyama Y, Furuichi T, Ikegawa S
J Hum Genet 2008;53(8):764-8. Epub 2008 Jun 14 doi: 10.1007/s10038-008-0305-z. PMID: 18553123
Czarny-Ratajczak M, Lohiniva J, Rogala P, Kozlowski K, Perälä M, Carter L, Spector TD, Kolodziej L, Seppänen U, Glazar R, Królewski J, Latos-Bielenska A, Ala-Kokko L
Am J Hum Genet 2001 Nov;69(5):969-80. Epub 2001 Sep 14 doi: 10.1086/324023. PMID: 11565064Free PMC Article
Paassilta P, Lohiniva J, Annunen S, Bonaventure J, Le Merrer M, Pai L, Ala-Kokko L
Am J Hum Genet 1999 Apr;64(4):1036-44. PMID: 10090888Free PMC Article

Recent systematic reviews

Marques LHS, Martins DV, Juares GL, Lorenzetti FTM, Monsanto RDC
Int J Pediatr Otorhinolaryngol 2017 Oct;101:223-229. Epub 2017 Aug 22 doi: 10.1016/j.ijporl.2017.08.020. PMID: 28964299
Miccoli M, Bertelloni S, Massart F
Horm Res Paediatr 2016;86(1):27-34. Epub 2016 Jun 30 doi: 10.1159/000446958. PMID: 27355624
Yu FF, Liu H, Guo X
Biol Trace Elem Res 2016 Dec;174(2):274-279. Epub 2016 Apr 26 doi: 10.1007/s12011-016-0712-5. PMID: 27113769
Yang L, Zhao GH, Yu FF, Zhang RQ, Guo X
Biol Trace Elem Res 2016 Mar;170(1):43-54. Epub 2015 Aug 8 doi: 10.1007/s12011-015-0463-8. PMID: 26250430
Jamieson B, Pope B
Emerg Med J 2010 Aug;27(8):625-6. doi: 10.1136/emj.2010.097766. PMID: 20688943

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