eMedicine Specialties > Orthopedic Surgery > Pediatrics
Multiple Epiphyseal Dysplasia
Updated: Jul 26, 2009
Introduction
History Of The Procedure
Thomas Fairbank described a patient with irregular ossification of multiple epiphyses in 1935. In 1947, he coined the term dysplasia epiphysealis multiplex and discussed its clinical and radiologic features.1
Problem
Among the osteochondrodysplasias, multiple epiphyseal dysplasia (MED) occurs most commonly. MED is characterized by involvement of multiple epiphyses with variable phenotypes. In general, MED is inherited in an autosomal dominant pattern; however, other inheritance forms are also seen.2,3,4
Anteroposterior (AP) radiograph of the pelvis shows bilateral hip changes.
Anteroposterior (AP) radiographs of the knee shows characteristic changes of multiple epiphyseal dysplasia (MED).
Frequency
Studies suggest a prevalence of 9-16 cases per 100,000 births.5,6
Etiology
The exact etiology of MED remains unclear. No potential causes or risk factors for MED are known. Genetic alterations result in abnormal enchondral ossification.
MED is a heterogeneous disorder. Mutations in several genes can cause the disease, including the following7,8 :
- COMP, which encodes cartilage oligomeric matrix protein (COMP)
- COL9A1, COL9A2, and COL9A3, which encode type IX collagen
- MATN3, which encodes matrilin-3 (MATN3)
- DTDST or SLC26A2, which encodes the diastrophic dysplasia sulfate transporter (DTDST or SLC26A2)
Most autosomal forms of MED are attributed to a COMP mutation.9 COMP is located on chromosome 19. Only a few cases of autosomal dominant MED are characterized by mutations affecting MATN3 and type IX collagen.
All recessive forms of MED are related to mutations in SLC26A2 and involve the peripheral joints.9
Pathophysiology
COMP and MATN3 are thought to bridge extracellular matrix proteins. Collagen IX is important for the adhesive properties of cartilage. Altered enchondral ossification may be associated with changes in the articular cartilage. The resultant articular cartilage is deficient in underlying osseous support and fails to withstand normal cyclical loading.10,11
Studies have revealed genotypic-phenotypic correlations.
- MED arising from COMP mutations is significantly associated with involvement of the proximal femur and acetabulum.12
- MED resulting from mutations affecting type IX collagen leads to severe involvement of the knees rather than the hips.
- Individuals with the recurrent R718W mutation in the COMP gene have a relatively mild form of MED.13
Presentation
General presentation
The autosomal dominant form of MED typically manifests late in childhood. At birth, the patient's external appearance is normal, and clinical features are seen in late childhood. The disease is not associated with visceral anomalies, and the patient's intelligence is in the normal range.
Autosomal recessive MED can be associated with anomalies that are apparent at birth. Examples of such anomalies are clubfoot, cleft palate, cystic ear swelling, or clinodactyly.
Variability in the phenotypes of MED may lead to variable presentations. Mild forms of the disease may remain undiagnosed, or they may be misdiagnosed as bilateral Perthes disease or early-onset osteoarthritis.
Patients with MED typically present with some or all the following features14 :
- Presentation late in childhood
- Pain in the hips and/or knees
- Early fatigue after exercise
- Gait abnormalities
- Elbow flexion contractures
- Angular deformities in the lower extremity
- Coxa vara
- Genu varum or valgum
- Valgus deformity at the distal tibia
- Shoulder pain with restricted abduction in patients with shoulder involvement
The shoulder joint becomes symptomatic in the fifth decade of life.
In rare cases, clubfeet, radial-ray deficiency, and/or scoliosis are observed.15,16
Height and weight
The height of patients with MED is normal or slightly less than normal. Their adult height is 145-170 cm.17,2 Motor development is normal.
Patients can be abnormally heavy for their height. In addition, they can have generalized muscle weakness and chronic musculoskeletal pain.18
Lower-extremity findings
Angular deformities are often seen in the lower extremity. Flexion contractures of the knee can also be seen. Osteochondritis dissecans may be present, especially in the knee joint. The patella may develop chronic subluxation or dislocation, and patients may have associated clicking and pain. Double-layered patellae (ie, the radiographic appearance of a patella with multiple layers) may be associated with subluxation or dislocation of the radial head and with a foot deformity.19
Bilateral involvement of the hip joints is seen in MED. Unilateral changes in 1 hip joint is a feature of conditions other than MED.
Upper-extremity findings
The upper extremities are involved less than the lower extremities are. MED can involve the shoulder, elbow, and/or wrist, but these structures are often asymptomatic. Clinical findings in the upper extremity include cubitus valgus and elbow flexion contracture.3
Spinal findings
By definition, the spine is normal in MED. However, scoliosis has been reported.16,3 For example, a 22º left thoracolumbar curve was measured in a patient at age of 13 months. The curve progressed to 53º at 6 years of age. The patient also had a right thoracic curve, which remained stable at 41º. An associated finding was thoracolumbar kyphosis. Bracing was ineffective in controlling the curve.
Differential diagnoses- Bilateral Perthes disease: Patients with bilateral Perthes disease may have normal stature. Features of MED include coxa vara with a short and widened femoral neck. In addition, the femoral head is fragmented and flat, and the acetabulum may be involved in patients with MED.
- Pseudoachondroplasia: Features of pseudoachondroplasia include marked ligamentous laxity and pes planovalgus in addition to short stature.
- Spondyloepiphyseal dysplasia: Typical features of spondyloepiphyseal dysplasia (SED) are spinal involvement, short stature, and involvement of the hands and feet. SED may also involve the eyes and lungs, and neurologic signs may be noted.
Indications
Indications for surgical intervention to manage MED are pain, subluxation of the joint, and angular deformity.
Relevant Anatomy
The relevant anatomy is specific to the joint involved. Altered anatomic features are discussed in Preoperative Details.
Contraindications
No specific guidelines about contraindications are available. Contraindications to surgical intervention to treat MED are the same as those for any other planned surgical procedure.
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References
Fairbank T. Dysplasia epiphysealis multiplex. Br J Surg. 1947;34:225-32.
Morrissy RT. Lovell and Winter's Pediatric Orthopaedics. 6th ed. Philadelphia, Pa: Lippincott Williams and Wilkins; 2006:233-4.
Sebik A, Sebik F, Kutluay E, et al. The orthopaedic aspects of multiple epiphyseal dysplasia. Int Orthop. 1998;22(6):417-21. [Medline].
Lachman RS, Krakow D, Cohn DH, Rimoin DL. MED, COMP, multilayered and NEIN: an overview of multiple epiphyseal dysplasia. Pediatr Radiol. Feb 2005;35(2):116-23. [Medline].
Andersen PE Jr, Hauge M. Congenital generalised bone dysplasias: a clinical, radiological, and epidemiological survey. J Med Genet. Jan 1989;26(1):37-44. [Medline].
Wynne-Davies R, Gormley J. The prevalence of skeletal dysplasias. An estimate of their minimum frequency and the number of patients requiring orthopaedic care. J Bone Joint Surg Br. Jan 1985;67(1):113-7. [Medline]. [Full Text].
Briggs MD, Chapman KL. Pseudoachondroplasia and multiple epiphyseal dysplasia: mutation review, molecular interactions, and genotype to phenotype correlations. Hum Mutat. May 2002;19(5):465-78. [Medline].
Rossi A, Superti-Furga A. Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene (SLC26A2): 22 novel mutations, mutation review, associated skeletal phenotypes, and diagnostic relevance [erratum in Hum Mutat 2001;18(1):82]. Hum Mutat. Mar 2001;17(3):159-71. [Medline].
Zankl A, Jackson GC, Crettol LM, et al. Preselection of cases through expert clinical and radiological review significantly increases mutation detection rate in multiple epiphyseal dysplasia. Eur J Hum Genet. Feb 2007;15(2):150-4. [Medline].
Mäkitie O, Mortier GR, Czarny-Ratajczak M, et al. Clinical and radiographic findings in multiple epiphyseal dysplasia caused by MATN3 mutations: description of 12 patients. Am J Med Genet A. Mar 15 2004;125(3):278-84. [Medline].
Stanescu R, Stanescu V, Muriel MP, Maroteaux P. Multiple epiphyseal dysplasia, Fairbank type: morphologic and biochemical study of cartilage. Am J Med Genet. Feb 15 1993;45(4):501-7. [Medline].
Unger S, Hecht JT. Pseudoachondroplasia and multiple epiphyseal dysplasia: New etiologic developments. Am J Med Genet. 2001;106(4):244-50. [Medline].
Jakkula E, Lohiniva J, Capone A, et al. A recurrent R718W mutation in COMP results in multiple epiphyseal dysplasia with mild myopathy: clinical and pathogenetic overlap with collagen IX mutations. J Med Genet. Dec 2003;40(12):942-8. [Medline].
Ingram RR. The shoulder in multiple epiphyseal dysplasia. J Bone Joint Surg Br. Mar 1991;73(2):277-9. [Medline].
Eddy MC, Steiner RD, McAlister WH, Whyte MP. Bilateral radial ray hypoplasia with multiple epiphyseal dysplasia. Am J Med Genet. May 18 1998;77(3):182-7. [Medline].
Herring JA. Rapidly progressive scoliosis in multiple epiphyseal dysplasia. A case report. J Bone Joint Surg Am. Jul 1976;58(5):703-4. [Medline].
Haga N, Nakamura K, Takikawa K, et al. Stature and severity in multiple epiphyseal dysplasia. J Pediatr Orthop. May-Jun 1998;18(3):394-7. [Medline].
Damignani R, Young NL, Cole WG, et al. Impairment and activity limitation associated with epiphyseal dysplasia in children. Arch Phys Med Rehabil. Oct 2004;85(10):1647-52. [Medline].
Sheffield EG. Double-layered patella in multiple epiphyseal dysplasia: a valuable clue in the diagnosis. J Pediatr Orthop. Jan-Feb 1998;18(1):123-8. [Medline].
Unger S, Bonafé L, Superti-Furga A. Multiple epiphyseal dysplasia: clinical and radiographic features, differential diagnosis and molecular basis. Best Pract Res Clin Rheumatol. Mar 2008;22(1):19-32. [Medline].
Bajuifer S, Letts M. Multiple epiphyseal dysplasia in children: beware of overtreatment!. Can J Surg. Apr 2005;48(2):106-9. [Medline].
Treble NJ, Jensen FO, Bankier A, et al. Development of the hip in multiple epiphyseal dysplasia. Natural history and susceptibility to premature osteoarthritis. J Bone Joint Surg Br. Nov 1990;72(6):1061-4. [Medline].
Mackenzie WG, Bassett GS, Mandell GA, Scott CI Jr. Avascular necrosis of the hip in multiple epiphyseal dysplasia. J Pediatr Orthop. Nov-Dec 1989;9(6):666-71. [Medline].
Miura H, Noguchi Y, Mitsuyasu H, et al. Clinical features of multiple epiphyseal dysplasia expressed in the knee. Clin Orthop Relat Res. Nov 2000;(380):184-90. [Medline].
van Mourik JBA, Weerdenburg JPG, Verhaar JAN. Magnetic resonance imaging of multiple epiphyseal dysplasia (type 2) of the knee. Radiography. 2001;7:61-4. [Full Text].
Hunt DD, Ponseti IV, Pedrini-Mille A, Pedrini V. Multiple epiphyseal dysplasia in two siblings. Histological and biochemical analyses of epiphyseal plate cartilage in one. J Bone Joint Surg Am. Dec 1967;49(8):1611-27. [Medline].
Pavone V, Costarella L, Privitera V, Sessa G. Bilateral Total Hip Arthroplasty in Subjects with Multiple Epiphyseal Dysplasia. J Arthroplasty. Sep 10 2008;[Medline].
Gardner J, Woods D, Williamson D. Management of double-layered patellae by compression screw fixation. J Pediatr Orthop B. Jan 1999;8(1):39-41. [Medline].
Lim SJ, Park YS, Moon YW, et al. Modular cementless total hip arthroplasty for multiple epiphyseal dysplasia. 2007;In press.
Further Reading
Keywords
MED, Fairbank disease, Fairbank's disease, MED Fairbank type, MED Ribbing type, combined Fairbank and Ribbing type, Fairbank-Ribbing type, MED unclassified, classic multiple epiphyseal dysplasia, classic MED, dysplasia epiphysealis multiplex, hereditary enchondral dysostosis, cartilage oligomeric matrix protein, COMP, COMP gene, type IX collagen, collagen IX, COL9A2 gene, COL9A3 gene, matrilin 3, matrilin-3, MATN3, MATN3 gene, diastrophic dysplasia sulfate transporter gene, DTDST, DTDST gene, SLC26A2, SLC26A2 gene, osteochondrodysplasia, inherited chondrodysplasias, abnormal enchondral ossification, spondyloepiphyseal dysplasia, SED
