Multiple Epiphyseal Dysplasia (MED)

Introduction

A form of dwarfism characterized by irregular, delayed ossification at multiple epiphyses
- spectrum of disorders with a spectrum of phenotypes
Epidemiology
- location
  - caused by failure of formation of secondary ossification center (epiphysis).
Genetics
- most commonly autosomal dominant
- defect in COMP (cartilage oligomeric matrix protein) gene on chromosome 19 (most common and most severe form)
- mutations in COL9A1, COL9A2, COL9A3
  - codes for type IX collagen
  - causing type II collagen dysfunction because of type IX collagen acts as a link protein for type II collagen

Presentation

Symptoms
- short-limbed dwarfism
- joint pain
- often does not manifest until ages 5 to 14 yrs
- waddling gait
Physical exam
- joint deformities from joint incongruity
  - valgus knee deformity common
  - early OA
- joint contractures common
- spine is usually normal

Imaging

Radiographs
- cervical spine
  - flexion-extension films may show instability of upper cervical spine
- pelvis
  - may show bilateral epiphyseal defects
    - may mimic Leg-Calve-Perthes (difference is MED hips are simultaneous and bilateral)
- knee
  - valgus knee
  - tibial "slant sign"
  - double layer patella
- hand
  - may show short, stunted metacarpals
  - hyperextensible fingers
- foot
  - short metatarsals

Treatment

Nonoperative
- NSAIDS and therapy
  - indications
    - early OA
Operative
- corrective osteotomy or hemiepiphysiodesis
  - indications
    - progressive genu valgum
- total hip arthroplasty
  - indications
    - severe arthritis
      - joint incongruity may lead to early arthritis and often requires total joint replacement early on in life.

TAG

(OBQ08.118) A 9-year-old boy presents for evaluation of shortened stature. He denies back or extremity pain. Physical exam is notable for a valgus left knee and a waddling gait. Radiographs of the pelvis, knees, and left hand are provided in figures A-C. Genetic testing reveals a mutation of the cartilage oligomeric matrix protein(COMP). What is the most likely diagnosis? Topic

Review Topic

FIGURES: A

1. Multiple epiphyseal dysplasia
2. Achondroplasia
3. Diastrophic dysplasia
4. Perthes disease
5. Metaphyseal chondrodysplasia

PREFERRED RESPONSE ▶

DISCUSSION: The clinical presentation and radiogaphs are consistent with Multiple epiphyseal dysplasia. Figure A demonstrates short, stunted proximal femur with epiphyseal irregularities and incongruity of the femoral head. Figure B demonstrates a valgus left knee and flattened femoral condyles. Figure C shows shortened metacarpals and irregularities throughout the epiphyses of the metacarpals and phalanges. Multiple epiphyseal dysplasia is caused by a mutation in the COMP gene that leads to delayed and irregular ossification of the epiphyses of the long bones. Merritt et al. describes a novel technique of creating COMP mutations in vitro to study pseudoachondroplasia and MED. Rimoin et al. used electron microscopy and genetic anaylsis to exclude an entire family of loci as the potential genetic cause of MED and psuedoachondroplasia. Ballock et al. reviews the biology and function of the growth plate. Pelvis radiographs of MED are classically similar to Perthes disease, the key difference being that changes occur simultaneously in both hips in MED.

REFERENCES:

1. Merritt, TM, Alcorn JL, Haynes R, Hecht JT: Expression of mutant cartilage oligomeric matrix protein in human chondrocytes induces the pseudoachondroplasia phenotype. J Ortho Res 2006;24:700-707 PMID:16514635 (Link to Abstract)

2. Rimoin DL, Rasmussen IM, Briggs MD, Roughley PJ, Gruber HE, Warman ML, OlsenBR, Hsia YE, Yuen J, Reinker K, et al. A large family with features of pseudoachondroplasia and multiple epiphyseal dysplasia: exclusion of seven candidate gene loci that encode proteins of the cartilage extracellular matrix.Hum Genet. 1994 Mar;93(3):236-42. PMID:7907311 (Link to Abstract)

3. Ballock RT, O'Keefe RJ. The biology of the growth plate. J Bone Joint Surg Am.2003 Apr;85-A(4):715-26 PMID:12672851 (Link to Abstract)

Question Authors:

John Badylak MD, Eric Shirley MD, Derek Moore,

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Textbooks

Review of Orthopaedics, 6th Edition, Mark D. Miller MD, Stephen R. Thompson MBBS MEd FRCSC, Jennifer Hart MPAS PA-C ATC, an imprint of Elsevier, Philadelphia, Copyright 2012
AAOS Comprehensive Orthopaedic Review, Jay R. Leiberman. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2009
Orthopaedic Knowledge Update 10, John M Flyn. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2011
Hoppenfeld SP. Surgical Exposures in Orthopaedics: The Anatomic Approach. Lipponcott, Williams, and Wilkins, Philadelphia, PA, Copyright 2009
Orthopaedic In-training Examination (OITE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012
Self-Assessment Examination (SAE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012

Undefined

Merritt, TM, Alcorn JL, Haynes R, Hecht JT: Expression of mutant cartilage oligomeric matrix protein in human chondrocytes induces the pseudoachondroplasia phenotype. J Ortho Res 2006;24:700-707 PMID:16514635 (Link to Abstract)
Rimoin DL, Rasmussen IM, Briggs MD, Roughley PJ, Gruber HE, Warman ML, OlsenBR, Hsia YE, Yuen J, Reinker K, et al. A large family with features of pseudoachondroplasia and multiple epiphyseal dysplasia: exclusion of seven candidate gene loci that encode proteins of the cartilage extracellular matrix.Hum Genet. 1994 Mar;93(3):236-42. PMID:7907311 (Link to Abstract)
Ballock RT, O'Keefe RJ. The biology of the growth plate. J Bone Joint Surg Am.2003 Apr;85-A(4):715-26 PMID:12672851 (Link to Abstract)

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