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Does it Always Have to be Perthes’ Disease?: What is Epiphyseal Dysplasia?

Hesse, B.*; Kohler, G.**

Clinical Orthopaedics and Related Research: September 2003 - Volume 414 - Issue - p 219-227
doi: 10.1097/01.blo.0000079272.91782.b1
SECTION II ORIGINAL ARTICLES: Pediatrics
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The epiphyseal dysplasias are classified as osteochondral dysplasias in a heterogeneous group of skeletal dysplasias. The common feature of these hereditary conditions is short stature attributable to skeletal dysplasia at various sites. Multiple epiphyseal dysplasia and spondyloepiphyseal dysplasia are of interest to the authors, because the two syndromes are similar in their morphologic features and at first glance suggest the diagnosis of Perthes’ disease. Spondyloepiphyseal dysplasia (Wiedemann-Spranger syndrome) is a disorder of growth in which there is an abnormality of enchondral ossification affecting the vertebral bodies and the epiphyses of the long bones. The two forms are the more severe congenita form (Type I), which is inherited as an autosomal dominant condition and is associated with a highly disproportional reduction in growth and severe coxa vara, and the milder tarda form which is an X-linked recessive condition, in which growth in adolescence is defective after normal childhood development. Multiple epiphyseal dysplasia is an abnormality of enchondral ossification, especially of the femoral head epiphysis, and it is an autosomal dominant condition. Depending on its severity, a distinction is made between the severe Fairbank form, the milder Ribbing form, and a mild localized Meyer form.

From the *Department of Orthopaedic Surgery, Kantonsspital St. Gallen, Switzerland; and the **Orthopaedic Department, University Children’s Hospital Basle, Switzerland.

Reprint requests to Beatrix Hesse, MD, Department of Orthopaedic Surgery, Kantonsspital, Rorschacherstr. 59, CH-9007 St. Gallen, Switzerland. Tel.: +41 71 494 1111; Fax: +41 71 494 2869; E-mail: beatrix.hesse@gmx.net.

Received: December 10, 2001.

Revised: June 13, 2002; August 27, 2002; November 14, 2002.

Accepted: December 3, 2002.

If a child or adolescent complains of prolonged nonspecific hip pain, sometimes associated with a limp or waddling gait, a thorough examination is necessary. The range of differential diagnoses is broad and varies among age groups (Table 1). In younger children (2–10 years), acute septic arthritis, Perthes’ disease, or an underlying rheumatic disease should be suspected primarily. If the children are older than 10 years, apart from slipped capital femoral epiphysis, femoral head necrosis, and inflammatory changes, a growth disorder attributable to one of the epiphyseal dysplasias also should be considered. Distinguishing mucopolysaccharidosis from pseudoachondroplasia is difficult. Both syndromes have similar radiologic deformities in the femoral head epiphyses and in the region of the vertebral bodies (platyspondylisis, dens hypoplasia, atlantoaxial instability). 36

TABLE 1

TABLE 1

Two children are described, one with spondyloepiphyseal dysplasia and the other with multiple epiphyseal dysplasia of the Meyer type (epiphyseal dysplasia of the femoral head) and characteristic features showing aspects of the differential diagnosis are discussed.

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PATIENT 1–SPONDYLOEPIPHYSEAL DYSPLASIA

A 13-year-old boy presented with pain in both hips for approximately 1 year. A waddling gait had become increasingly obvious. Because of familial small stature and psychomotor developmental delay, he had been examined as a small child (at 4 years). Hormonal dysfunction (lack of growth hormone), metabolic disorders, and thyroid disorders had been excluded.

At the age of 4 years, his height was 13 cm below the third percentile. Growth since then was below the third percentile and he was 14 cm below the third percentile at the age of 13 years. Psychomotor and, in particular, speech development were markedly retarded.

In the family history, the mother is of disproportionately small stature with a height of 144 cm and the father was 172 cm. The patient is the fourth of five children. One sister has no corpus callosum, marked epilepsy, and mental retardation, and three of the other siblings are of small stature and also have educational problems.

The findings on clinical examination showed a sturdy boy 131 cm tall and weighing 34.6 kg. His arm span was 140 cm, seated height was 69.5 cm, and the subischial leg length was 61.6 cm. There was a waddling gait, seen with barefoot gait, and toe to heel gait was possible. Functional examination of the spine and hips showed unrestricted and pain-free mobility. Radiographs of the pelvis and both hips showed marked loss of height of both femoral heads, multiple fragments with shortening of the femoral neck, and marked irregularity of the acetabular outline with an increased acetabulum-center angle (Fig 1). Radiographs of the spine showed general narrowing of the intervertebral spaces and absence of the normal outline of the vertebral bodies in the lower thoracic and upper lumbar region with ossification defects of the anterior third of the upper and lower surfaces of the vertebral body with a tongue-shaped anterior margin (Fig 2).

Fig 1A–B.

Fig 1A–B.

Fig 2A–C.

Fig 2A–C.

According to Greulich and Pyle 12 the skeletal age was 13 years 2 months as determined from a radiograph of the hand. According to Bailey and Pinneau 2 an adult height of 148.6 cm can be expected.

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PATIENT 2–MULTIPLE EPIPHYSEAL DYSPLASIA (EPIPHYSEAL DYSPLASIA OF THE FEMORAL HEAD TYPE)

The boy was first referred at the age of 6 years for assessment of toeing-in and dragging the left leg. Back pain had been occurring for some time and the patient’s legs fatigued rapidly. Clinically, hip mobility was normal bilaterally, there was a Trendelenburg limp on the left, and weakness of the gluteal muscles on the left. Increased body hair on the legs and back also was seen. This was assessed as constitutional by the endocrinologist, therefore no laboratory investigations were done as the history was unremarkable. On the basis of the radiographs, the diagnosis of incipient Perthes’ disease on the left was made. At the age of 7 years 2 months, the patient had severe pain in the back independent of movement and alternating in the two hips. A waddling gait was seen and movement at the end of flexion and rotation was painful. In the next 6 months, severe pain developed and using stairs became impossible. Epiphyseal dysplasia was suspected radiologically because there was no tendency of dislocation of the femoral head. The nuclei of the femoral heads showed irregular ossification, were slightly widened, and had increasing sclerosis. Examination of mobility at the age of 8 years 8 months showed restriction in abduction, adduction, and in rotation. The range of motion (ROM) was 10° abduction to 10° adduction on the right and 30° abduction to 20° adduction on the left. The internal and external rotation was 10° on both sides, therefore the patient needed inpatient physiotherapy including wearing a plaster cast in abduction. This was followed by arthroscopic hydraulic mobilization of the right hip (arthroscopy of the joint and filling with gas to stretch the capsular structures) and mobilization of the left hip with the patient under anesthesia, which improved mobility to 50° abduction and to 30° adduction bilaterally. The ROM in internal rotation improved to 45° on the left and to 25° on the right and in external rotation to 30° bilaterally.

At 9 years the patient had a ROM in abduction to adduction from 50° to 20° bilaterally and internal to external rotation from 25° to 30° on the right and from 40° to 60° on the left (examination with flexed hip). The patient was 130 cm tall and therefore is less than the forty-fifth percentile.

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DISCUSSION

Epiphyseal dysplasia is attributable to an abnormality of enchondral growth in which the bony structure of the epiphysis is disturbed. This is an inherited disorder, which can occur as multiple epiphyseal dysplasia or as spondyloepiphyseal dysplasia.

Multiple epiphyseal dysplasia has been linked to abnormalities in cartilage oligomeric matrix protein, 4 and spondyloepiphyseal dysplasia has been linked to mutations in Type II collagen. 7 Endocrine associations were suspected when hypothyroidism or diabetes mellitus occurred at the same time 35 and also with collagen changes or degenerative lysosomal processes when a proteoglycan was produced. 7 Apart from Perthes’ disease, pseudoachondroplasia and mucopolysaccharidosis Type IV (Morquio’s syndrome) should be considered first in the differential diagnosis, especially when the spine is involved. Various investigations are necessary to make the diagnosis, including clinical examination, followup radiographs, and biochemical tests to exclude enzyme deficiencies. This results in an overall picture which should make a diagnosis possible (Table 2).

TABLE 2

TABLE 2

TABLE 2

TABLE 2

The changes in the femoral head can be similar to Perthes’ disease (Fig 3). However, the following radiologic findings suggest the diagnosis of epiphyseal dysplasia: bilateral symmetric hip involvement, few cystic and sclerotic changes in the femoral head, co-involvement of the acetabulum, absence of a tendency to lateral calcification and subluxation, and involvement of the spine or other joints. 1,16

Fig 3A–B.

Fig 3A–B.

Perthes’ disease is bilateral in 15%11 and shows asymmetric irregularities in the region of the femoral heads, 8 and cystic changes are found not only in the epiphyses of the proximal femur but often in the metaphysis. 1 Clear differentiation from Perthes’ disease is difficult and the gender distribution provides no indication (boys are affected four times more often).

The distinction is important because the prognosis of spondyloepiphyseal dysplasia and epiphyseal dysplasia Type I 10 is worse compared with Perthes’ disease 37 and the indication for therapeutic intervention is more guarded. 1,32 Nevertheless, measures to improve mobility can become necessary as in Patient 2 with multiple epiphyseal dysplasia in the current study. If increasing movement deficits develop despite intensive physiotherapy, the authors try initially to improve the ROM (especially abduction and internal rotation) by inpatient physiotherapy. If this is not successful, the authors regard this, as with Perthes’ disease, as an indication for more aggressive management with mobilization under anesthesia and arthroscopic mobilization, if necessary. If abduction has been achieved successfully, a plaster bed in maximum abduction is made and physiotherapy is continued for several days under epidural anesthesia. 16

Small stature, platyspondylia, symmetric radiologic changes in the hips, and changes in the end-plates of long bones suggest the diagnosis of spondyloepiphyseal dysplasia. 13 Distinction from mucopolysaccharidosis Type IV (Morquio’s syndrome) and pseudoachondroplasia is difficult, as there are similar changes in the spine. The presence of flat oval vertebral bodies is characteristic. 18,28 According to Maroteaux and Lamy 23 the anterior tongue-shaped projections of the vertebral bodies are typical changes. These can be explained by the defective development of the ring apophyses and recall Morquio’s disease primarily. 26 Morquio-Brailsford disease initially was classified as intermediate spondyloepiphyseal dysplasia. After increased keratosulfate excretion in the urine was found in this syndrome, it was assigned to the mucopolysaccharidoses. 20 The biochemical finding of keratosulfate in the urine attributable to a lysosomal defect is regarded as the most important differential diagnostic criterion for identifying Type IV mucopolysaccharidosis. 3,26 The normal development of the teeth, the mandible, the ribs, and the sternum, and the absence of hepatomegaly and kyphoscoliosis argue against the presence of Morquio syndrome. 13

The most important evidence for the presence of pseudoachondroplasia, apart from shortening of the torso and the limbs, is coarseness of the hands and feet, massive ligament laxity associated with genua vara and recurvata, instability of the ankles, and the marked pes plano-valgus. 23 Pseudoachondroplasia also can be distinguished successfully from spondyloepiphyseal dysplasia tarda because of the time that the illness appears and because of the fact that a short torso develops with less limb shortening. 13,22,28

Deposition of an abnormal proteoglycan in cartilage has been reported, 29 abnormalities in cartilage oligomeric matrix protein were found, similar to epiphyseal dysplasia. 4

In individual case reports of spondyloepiphyseal dysplasia, retinal detachment, myopia, cataract, and isolated cases of impaired hearing have been reported. The causes for this have not been elucidated. 21,28 An association of spondyloepiphyseal dysplasia with nephrotic syndrome with proteinuria, hypoalbuminemia, hypercholesterolemia, and edema also was observed. 9

In individual cases, multiple epiphyseal dysplasia is associated with progressive arthropathy. The first symptoms in the form of joint symptoms and finger swelling occur in childhood, suggesting a diagnosis of juvenile chronic arthritis. When epiphyseal dysplasia is present, the typical radiologic alterations of rheumatoid arthritis (erosions, periosteal reactions) will not be evident; clinically, there is no joint swelling attributable to synovitis, and morning stiffness and inflammatory joint pains also are absent. 5,13

Other diseases, such as achondroplasia, diastrophic dwarfism, Pfaundler-Hurler’s disease, hemimelic epiphyseal dysplasia, and punctate hemimelic dysplasia can be distinguished from the described syndromes on the basis of the characteristic clinical appearance, the radiologic findings, and the laboratory investigations.

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