Multiple Epiphyseal Dysplasia

Updated: Dec 13, 2021
Author: Ashish S Ranade, MBBS, MS, FRCS(Glasg); Chief Editor: Jeffrey D Thomson, MD 


Practice Essentials

Multiple epiphyseal dysplasia (MED) is a rare genetic disorder that affects the growing ends of bones. In 1935, Thomas Fairbank described a patient with irregular ossification of multiple epiphyses; in 1947, he coined the term dysplasia epiphysealis multiplex and discussed the clinical and radiologic features of this condition.[1]  Although the term Fairbank disease is sometimes used, MED is the name more frequently used in current practice.

Of the osteochondrodysplasias, MED is the most common. Studies suggest a prevalence of 9-16 cases per 100,000 births.[2, 3]  MED is characterized by involvement of multiple epiphyses with variable phenotypes.[4]  In general, MED is inherited in an autosomal dominant pattern[5] ; however, other inheritance forms are also seen.[6, 7, 8]

The goals of medical management of MED are to alleviate pain and to halt joint destruction and the development of early osteoarthritis. The goals of surgical therapy are pain relief, correction of angular deformities, and correction of joint contractures. Indications for surgical intervention to manage MED are pain, subluxation of the joint, and angular deformity. No specific guidelines about contraindications are available; contraindications for surgical intervention to treat MED are the same as those for any other planned surgical procedure.


Cartilage oligomeric matrix protein (COMP) and matrilin-3 (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.[9, 10]

Studies have revealed the following genotypic-phenotypic correlations:

  • MED arising from COMP mutations is significantly associated with involvement of the proximal femur and acetabulum [11]
  • 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 [12]
  • MED arising from MATN3 mutations tends to have milder clinical manifestations than MED caused by  COMP mutations [13]


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. It can be caused by mutations in several genes, including the following[14, 15] :

  • COMP, which encodes COMP
  • COL9A1, COL9A2, and COL9A3, which encode type IX collagen
  • MATN3, which encodes MATN3
  • DTDST or SLC26A2, which encodes the diastrophic dysplasia sulfate transporter (DTDST or SLC26A2)
  • SMOC2, which encodes SPARC-related modular calcium binding protein 2

Most autosomal dominant forms of MED are attributed to a COMP mutation.[16]  COMP is located on chromosome 19. Only a few cases of autosomal dominant MED are characterized by mutations in MATN3,COL9A1, COL9A2, or COL9A3. A 2019 report implicated a novel COL2A1 mutation in an autosomal dominant form of MED in a large multigenerational family.[17]

All recessive forms of MED are related to mutations in SLC26A2 and involve the peripheral joints.[16]


Few investigators have described the outcomes of surgical treatment for MED. Lim et al reported on total hip replacement with the use of modular cementless prostheses.[18] At a mean follow-up of 4.8 years, no hip required revision. Harris hip scores seemed to be substantially improved.



History and Physical Examination

General presentation

The autosomal dominant form of multiple epiphyseal dysplasia (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, and 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[19] :

  • Presentation late in childhood
  • Pain in the hips, knees, or both
  • Early fatigue after exercise
  • Gait abnormalities
  • Elbow flexion contractures
  • Angular deformities in the lower extremity - Coxa varagenu 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, or scoliosis may be observed.[20, 21]

Height and weight

The height of patients with MED is normal or slightly less than normal. Their adult height is 145-170 cm.[22, 6] Motor development is normal. Patients with MED can be abnormally heavy for their height. In addition, they can have generalized muscle weakness and chronic musculoskeletal pain.[23]

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.[24]

Bilateral involvement of the hip joints is seen in MED. Unilateral changes in one hip joint is a feature of conditions other than MED.

Upper-extremity findings

The upper extremities are less involved in MED than the lower extremities are. MED can involve the shoulder, elbow, or wrist, but these structures are often asymptomatic. Clinical findings in the upper extremity include cubitus valgus and elbow flexion contracture.[7]

Spinal findings

By definition, the spine is normal in MED. However, scoliosis has been reported.[21, 7] For example, a 22º left thoracolumbar curve was measured in a patient at the 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.



Diagnostic Considerations

Other conditions to be considered in the diagnosis include the following:

  • Bilateral Legg-Calvé-Perthes disease - Patients with this condition may have normal stature; features of multiple epiphyseal dysplasia (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 (SED) - Typical features of 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

Differential Diagnoses



Approach Considerations

The initial diagnosis of multiple epiphyseal dysplasia (MED) is typically based on clinical and radiographic features, though molecular genetic testing is available. Molecular genetic testing has a role in confirming the clinical diagnosis and in establishing an antenatal diagnosis.[16, 25]

Imaging studies that may be relevant to the evaluation of MED include the following:

  • Radiography
  • Magnetic resonance imaging (MRI)
  • Radioisotopic bone scanning

However, bone scanning, MRI, and ultrasonography (US) are not necessary to confirm the diagnosis of MED.


Although the cervical spine is not typically involved, the acquisition of flexion-extension radiographs may be prudent if surgery is being considered. Radiographs of major joint areas show a delay in the appearance of ossification centers in the long tubular bones. The epiphysis is small, fragmented, and irregular. In rare instances, metaphyseal irregularities and streaking may be seen. These changes are most pronounced in the hip and the knee. (See the image below.)

Radiograph shows alignment of the lower extremitie Radiograph shows alignment of the lower extremities.


Irregularities of the femoral head are evident by the first year of life. The secondary center of ossification in the femoral head may appear as late as 30 months of age. Epiphyseal fragmentation is evident by 10 years of age.[26]  Increased fragmentation of the capital epiphysis is associated with an early onset of osteoarthritis.[27]  Coxa vara may be seen in some patients. Avascular necrosis (AVN) may be superimposed on the typical changes observed in MED. AVN is associated with changes such as metaphyseal cysts and the crescent sign.[28]  Acetabular involvement occurs in MED. (See the image below.)

Anteroposterior (AP) radiograph of the pelvis show Anteroposterior (AP) radiograph of the pelvis shows bilateral hip changes.


Radiographic changes in the knee (see the image below) are typically described as those noted before or after the epiphyses close.

Anteroposterior (AP) radiographs of the knee shows Anteroposterior (AP) radiographs of the knee shows characteristic changes of multiple epiphyseal dysplasia (MED).

Changes before epiphyseal closure include the following:

  • Irregularity and segmentation of epiphysis
  • Widening of the joint space and angular deformity (eg, genu valgum)

Changes after epiphyseal closure include the following:

  • Shallow femoral trochlear groove (seen in >50% of patients)
  • Early-onset osteoarthritic changes
  • Depression of the lateral tibial plateau
  • Genu valgum
  • Multiple loose bodies

The presence of genu varum or valgum with loose bodies and premature osteoarthritis warrants radiographic evaluation of other joints. The clinician should keep in mind the possibility of MED. Double-layered patellae have been described with MED.[24]  Both knees are typically involved. A double-layered patella has anterior and posterior components.

Investigators have described a relationship between the shape of the femoral trochlear groove and the rate at which osteoarthritis develops. Three types of grooves have been described: shallow, normal, and an inverted V.[29]  The most common finding in this study was a shallow femoral trochlear groove, which was recorded in 56.5% of 31 patients, followed by irregularity of the articular surface, which was seen in 43.5%.

Foot and ankle

Foot and ankle findings (see the images below) include the following:

  • Valgus deformity of the distal tibia
  • Hypoplasia of the tarsal bones
Anteroposterior (AP) radiographs of the feet. Anteroposterior (AP) radiographs of the feet.
Lateral radiographs of the right and left feet. Lateral radiographs of the right and left feet.


Shoulder findings include the following[19] :

  • Minor epiphyseal involvement
  • Severe involvement (hatchet head group) - Malformed humeral head; broad metaphysis; bowing of the proximal shaft; hypoplasia of the glenoid


Elbow findings include the following:

  • Cubitus valgus
  • Osteochondral loose bodies


Hand findings include the following:

  • Ivory epiphyses
  • Short phalanges and metacarpi (variable feature)


Spinal findings include the following:

  • Schmorl nodes and endplate irregularities (rare)
  • Scoliosis (rare)

Magnetic Resonance Imaging

In a report on young patients, MRI findings included irregular and delayed ossifications of the epiphyses.[30]  The articular cartilage had a normal appearance, and no edema was observed. Neither joint effusion nor loose bodies were noted. Conventional radiography and MRI showed that the ossified parts of the epiphyses had similar shapes. Findings in the menisci and ligaments were unremarkable. MRI and conventional radiography provided the same information about the epiphysis in young patients with MED.

In the same report, both T1- and T2-weighted MRI showed a homogeneous hyperintensity of the epiphyses in patients aged 16-18 years.[30] MRI also showed homogeneously thick cartilage without clefts. However, plain radiography showed a defect in these cases. MRI did not depict osteochondritis dissecans or any free bodies. The ligaments and menisci were normal. The authors inferred that MRI did not give any additional information about the cause of the complaints in these adolescent patients.

In young children, MRI of the hip joint reveals irregularity of the proximal femoral epiphyses, diffusely decreased signal intensity, and a typical garland formation of the epiphyseal plate.

Bone Scanning

Radioisotopic bone scans can be used to diagnose AVN superimposed on MED.


Arthrography has been used to evaluate the hip joint in children. In young individuals with MED, the articular surface of the joint is intact.


Hip arthroscopy has been used to treat acute and semiacute pain in MED. Hip arthroscopy has shown the involvement of hip in the form of chondral avulsion fractures, loose bodies, labral tears, femoral head/acetabular chondromalacia, and chondral flaps.[31]

Histologic Findings

Intracytoplasmic inclusions are seen in MED. These are similar to but not as severe as those observed in pseudoachondroplasia. Abnormal organization of the growth plate is a clinically significant finding of MED. Other histologic findings are disordered columns of cartilaginous cells, clefts, and areas of degeneration in the matrix.[32] Some changes are seen in the metaphysis.



Medical Therapy

The goals of medical management of multiple epiphyseal dysplasia (MED) are as follows:

  • To alleviate pain
  • To halt joint destruction and the development of early osteoarthritis

Pain management can be challenging in MED; therefore, a physical therapy program with adequate analgesia is important. Patients benefit from a referral to a rheumatologist or a pain management specialist.

Weight management is also important. When clinicians prescribe physical therapy, they should avoid recommending specific exercises that exert repetitive stresses on the patient's affected joints.

Kim et al reported favorable midterm outcomes with conservative management in 40 patients with hip joints affected by MED.[33]

Surgical Therapy

The goals of surgical therapy for MED are as follows:

  • Pain relief
  • Correction of angular deformities
  • Correction of joint contractures

Treatment options include realignment procedures and arthroplasty to manage advanced osteoarthritis.

Preoperative planning plays an important role in the surgical treatment of patients with MED. Factors to consider in the planning of total knee replacement include the following:

  • Malpositioning of the tibial tubercle
  • Hypoplasia of the femoral condyle
  • Subluxation of the patella

In surgical treatment of the hip, it is important to account for the altered anatomy of the proximal femur and the patient's young age. In particular, it is vital to address the following altered anatomic features:

  • A large femoral head, which is deficient in acetabular coverage
  • A short femoral neck
  • Coxa vara
  • A high greater trochanter


Hip arthroscopy has been used for the treatment of acute or semiacute changes in hip pain in patients with MED.[31] A wide spectrum of intra-articular pathologies (eg, labral tears, chondral flaps, and loose bodies) can be addressed by means of arthroscopy. However, this treatment is palliative, and these patients develop early osteoarthritis.

A painful or subluxed skeletally immature hip is treated with surgical intervention. An acetabular shelf procedure can be done for coverage. Preexisting coxa vara often precludes femoral varus-producing osteotomy. In one report, good outcomes in terms of deformity correction were achieved by using intertrochanteric extension osteotomy and trochanteric arthroplasty.[34]

Medial displacement osteotomy (Chiari osteotomy) has been used to treat symptomatic patients with painful hips. In a study by Andrzejewski et al, 14 patients were reported to have favourable outcomes.[35] The Chiari osteotomy was found to reduce the pain, improve the hip function, and delay the need for total hip arthroplasty.

Patients with MED tend to develop early-onset osteoarthritis. They become symptomatic in the second or third decade of life. Total joint arthroplasty is the last resort for the management of advanced osteoarthritis.[36]  Patients with MED or other musculoskeletal dysplasias who undergo total joint arthroplasty may be at increased risk for surgical-site infection and perioperative hemorrhage, possibly because of the anatomic complexity encountered.[37]

Angular deformities

Angular deformities can be corrected by means of realignment osteotomy performed near the time of skeletal maturity or by means of hemiepiphyseal stapling.[38] In a study that used stapling for angular deformity correction, it was observed that physeal behavior after staple removal was unpredictable, and overcorrection should be avoided.


Treatment options for the knee include the following:

  • Corrective osteotomy for the femur, the tibia, or both to correct angular deformity
  • Removal of loose bodies

Treatment options for a double-layered patella in symptomatic patients include the following[39] :

  • Excision of one fragment
  • Fusion of two fragments

For the treatment of osteoarthritis, total knee replacement is necessary.


Complications that may arise after surgical treatment of MED include the following:

  • Recurrence of deformities
  • Aseptic loosening of prosthetic components
  • Intraoperative or postoperative periprosthetic fractures

Long-Term Monitoring

In addition to standard postoperative care, a comprehensive multidisciplinary approach is important and essential for rehabilitation.

Regular follow-up is important after any surgical intervention. Such follow-up is necessary to monitor the patient for progression to osteoarthritis after he or she undergoes any realignment procedure. Also, continuing care enables the clinician to detect signs of loosening and periprosthetic fractures after total joint arthroplasty; the incidence of these complications is high.