Spondyloepiphyseal Dysplasia Workup

• Fine metachromatic inclusions have been described in peripheral lymphocytes. The urinary excretion of acid mucopolysaccharides, including keratosulfate, is normal in patients with SED, in contrast to that in patients with Morquio disease.

• Radiographic imaging in patients with SED congenita: According to Spranger and Langer,^[2] a complete skeletal survey is warranted in the initial assessment. This includes anteroposterior and lateral skull, cervical skull with anteroposterior, open mouth, and lateral views in flexion, neutral, and extension; posteroanterior views of the wrist and hand; anteroposterior and lateral projections of the elbows, hips, and knees; anteroposterior and lateral views of the thoracolumbar vertebrae; and an anteroposterior film of the lumbar and sacral regions.^[25]

  • A generalized delay occurs in the development of ossification centers. The epiphyseal centers of the distal femur and proximal tibia, os pubis, calcaneus, and talus, which are usually present at birth, are absent in these patients. The femoral heads may not be apparent on radiographs until patients are aged 5 years. When the epiphyses do appear, they are flattened and irregular in shape (see image below). Spondyloepiphyseal dysplasia. Radiograph of the pelvis depicting delayed ossification of capital femoral epiphyses, metaphyseal flaring, horizontal acetabular roofs, triangular fragment on the inferior aspect of the broad femoral neck, and coxa vara.
  • Varying degrees of platyspondyly are present, with posterior wedging of vertebral bodies giving rise to oval, trapezoid, or pear-shaped vertebrae, as seen in the image below. The ossification of the bodies may be incompletely fused, as depicted in frontal projection. In adolescents and young adults, end plate irregularities and narrowed intervertebral disk spaces become obvious with an increased anteroposterior diameter of the vertebral bodies. Lumbar lordosis is usually exaggerated. Progressive kyphoscoliosis may develop in late childhood. The most marked abnormality is usually at the thoracolumbar junction, where gross ventral hypoplasia may be present. Spondyloepiphyseal dysplasia. Radiograph of the spine depicting increased anteroposterior diameter, platyspondyly, posterior wedging of the vertebrae, and increased lumbar lordosis.
  • Skull examination may reveal a steep anterior base, with the angle between the floor of the anterior fossa and clivus reaching up to 165° (compared to 110-145° in healthy individuals). Odontoid hypoplasia or os odontoideum leading to atlantoaxial instability is common, as seen in the first image below. Flexion-extension lateral cervical radiographs may reveal anterior, posterior, or anteroposterior instability. The thorax is broad and bell-shaped, as seen in the second image below, and the ribs may flare at the anterior ends. The costovertebral angles are increased, and the intercostal spaces are narrow. Spondyloepiphyseal dysplasia. Radiograph of the upper cervical vertebrae depicting ununited odontoid process. Spondyloepiphyseal dysplasia. Radiograph of the chest, depicting bell-shaped chest and decreased height of the trunk due to platyspondyly.
  • The iliac crests are short and small, with horizontal acetabular roofs and delayed ossification of the pubis. The iliac bones are small in their cephalocaudad dimension, with lack of normal flaring of the iliac wings. The Y cartilage is wide. The acetabular fossae are deep and appear empty due to the severely retarded ossification of femoral heads. Coxa vara of varying severity is almost always present (see image below) Spondyloepiphyseal dysplasia. Radiograph of the pelvis depicting delayed ossification of capital femoral epiphyses, metaphyseal flaring, horizontal acetabular roofs, triangular fragment on the inferior aspect of the broad femoral neck, and coxa vara.
  • In patients with severe coxa vara, progressive varus deformity may occur, leading to discontinuity of the femoral neck and proximal migration of the greater trochanter. The femoral shafts ride high under the iliac wings, and pseudoarticulation of the greater trochanters with the lateral margins of iliac crest is suggested.
  • The delayed ossification of the femoral head predisposes the hip to deformation with flattening, lateral extrusion, hinge abduction, and premature osteoarthritis. Ossification of the femoral head and neck proceeds slowly, frequently from multiple foci. The metaphyseal line of ossification frequently has a mottled appearance, and the femoral heads appear mottled and granular.
  • The ossification centers of the distal femur and proximal tibia are delayed, leading to flattening and irregularity. Genu valgum is usually present, with overgrowth of the medial femoral condyle. Mild flaring of the metaphyses of long tubular bones may be present, along with irregular ossification from alterations in endochondral bone formation. Full-length radiographs of the lower extremity may be indicated to depict the overall alignment before surgical procedures of the hip or knee.
  • The long tubular bones are relatively short and broad. Some metaphyseal flaring is present, especially in the region of the distal femur and proximal and distal humerus. The short tubular bones of the hands and feet are minimally broadened and shortened. Ossification of carpal and tarsal centers is usually delayed or disorganized, with occasional extra epiphyses. Wynne-Davies reported on the appearance of an epiphysis at the base of the second metacarpal, first seen in the patient at age 1-2 years.
• Radiographic imaging in patients with SED tarda: Changes may not be apparent in radiographic images in children younger than 4-6 years. Changes suggestive of atlantoaxial instability, platyspondyly, kyphoscoliosis, and epiphyseal involvement are similar to those seen in patients with SED congenita. However, the thoracic spine is typically involved to a greater extent in SED tarda. In the X-linked recessive type of SED tarda, a mound of bone is typically present in the central and posterior portions of the superior and inferior end plates. These changes are seen on lateral radiographs and are not features of the autosomal dominant or recessive types of SED tarda.

  • Epiphyseal involvement in SED tarda is primarily in the shoulders, as seen in the image below, hips, and knees symmetrically. For the weightbearing joints of the lower extremities, delayed ossification predisposes the joint to deformation and premature osteoarthritis. Changes in the hip may mimic bilateral Legg-Calve-Perthes disease. Spondyloepiphyseal dysplasia. Radiograph of shoulder, depicting severe epiphyseal involvement of proximal humerus, leading to premature osteoarthritis.
  • Varying degrees of coxa magna, flattening, extrusion, and subluxation are present.
• Magnetic resonance imaging

  • Cervical myelopathy may result from C1-C2 instability. Magnetic resonance imaging (MRI) can be used to delineate cord compression. MRI may be obtained prior to surgical intervention in patients with severe spinal deformities.
  • MRI may be used to evaluate the condition of the epiphyseal centers prior to reconstructive procedures.
• Hip arthrography

  • Hip arthrography may be indicated to document congruity of the femoral head or hinge abduction.
  • Severe varus deformity of the cartilaginous femoral neck is usually present and can be depicted on arthrography.
• Computed tomography scan

  • Computed tomography (CT) scan may be used to assess the configuration of bones and joints prior to surgical intervention.
  • Three-dimensional reconstructed images may help in surgical planning in severe cases.

• Prenatal testing

  • Although the gene for SED congenita has been located, its location is variable. Prenatal gene testing is available.
  • Prenatal testing for SED tarda may be offered based on molecular diagnosis.

Yang et al described the pathologic findings in patients with SED.^[26] Abnormalities of the proliferative zone have been identified, with microcystic areas surrounded by a ring of cells. The chondrocytes of the resting zone appear vacuolated, containing periodic acid-Schiff (PAS)–positive cytoplasmic inclusions. Ultrastructural examination revealed these inclusions to be accumulations of fine granular material in dilated cisterns of rough endoplasmic reticulum. However, heterogeneity is present, and these findings are not consistent.