Multiple Epiphyseal Dysplasia 

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]

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]}

Frequency

Studies suggest a prevalence of 9-16 cases per 100,000 births.^{[5, 6]}

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 following^{[7, 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]

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]

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 features^[14] :

• 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 for surgical intervention to manage MED are pain, subluxation of the joint, and angular deformity.

The relevant anatomy is specific to the joint involved. Altered anatomic features are discussed in Preoperative Details.

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.