Diastrophic Dysplasia Workup

• Laboratory tests may include a determination of serum calcium, phosphate, alkaline phosphatase, and protein to exclude hypophosphatasia and hypophosphatemia.
• Urine should be screened for storage products in cases of progression.
• Cytogenetic studies can be used for DNA and mutational analyses to confirm the diagnosis, either prenatally or postnatally.

• Radiography: A skeletal survey, including lateral imaging of the head and neck, and anteroposterior imaging of the entire spine, pelvis, arms, hands, and legs, should be requested.^[24]

  • Skull findings are normal initially, although calcifications develop in the pinna of the ear and later in the cranium. Precocious calcification of laryngeal and costal cartilages is a typical feature. A double-layered manubrium has been reported in 81% of patients. The most common finding is an accessory ossification center located ventral to the cranial part of the manubrium. In older patients, this ossification center may fuse with the main part of the manubrium, giving the appearance of an anteriorly bulging manubrium.
  • The spine has normal vertebral body height and breadth, and scoliosis is not present at birth. Developmental anomalies of the vertebra are unusual. Kyphosis and subluxation may be evident in the cervical spine, as seen in the first two images below. Cervical spina bifida occulta is present in almost all patients. Progressive scoliosis usually begins in the first year of life and may become severe. It may occur in the form of either a sharp angular curve, as seen in the third image below, or a gradual idiopathic curve. The interpedicular distances narrow only slightly at descending levels of the lumbar spine, unlike the findings in achondroplasia. Scoliosis in a patient with diastrophic dysplasia. The curve is a mild, nonprogressive-type curve. Note the degenerative changes associated with the scoliosis. Radiograph of the cervical spine obtained with the neck in neutral alignment shows severe kyphosis between C2 and C6 in a patient with diastrophic dysplasia. Early progressive type of scoliosis in a patient with diastrophic dysplasia. These curves typically have short segments and are sharply curved; they may have associated dysplastic changes in the vertebrae.
  • Pelvic configuration findings are abnormal, with some distortion of the iliac bones and posterior tilting of the sacrum. The acetabular roofs are widened and irregular, but unlike the findings in achondroplasia, the sacrosciatic notches are normal.
  • The long bones are short and thick and appear relatively massive. The mild metaphyseal broadening and flaring seen in the neonatal period increases markedly with growth, as seen in the image below. Both the ulna and fibula are shortened, contributing to the valgus of the knees and radial head subluxation. Epiphyseal development is delayed in the major limb articulations, and these epiphyses, when they do appear, are flattened and irregular. In the newborn, these flattened epiphyses may have a stippled appearance. The humerus in a patient with diastrophic dysplasia. Typically, all of the long bones are short and thick. Note the epiphyseal flattening and irregularity of the proximal humeral epiphysis. Metaphyseal flaring of the distal humerus is present.
  • At birth, the distal and capital femoral epiphyses are absent. In one study, the proximal femoral ossific nuclei had not appeared in 20% of patients by the age of 12 years. In childhood, the femoral necks are short and broad with a prominent trochanteric region. The capital femoral epiphyses show flattening, irregularity, and inferomedial bulking. The acetabulum is shallow, with a double-hump configuration. The changes in the hip lead to secondary osteoarthritis before early middle age, as seen in the images below. The distal femoral epiphyses appear to be medially displaced, perhaps due to underossification of the lateral portions. Pelvis with both hips in an adult with diastrophic dysplasia. Note the dysplastic shape of the femoral head, along with characteristic degenerative changes. Pelvis and both hips in a patient with diastrophic dysplasia. Note the short and broad neck of the femur. The appearance of the femoral epiphyses is delayed. Flattening of the epiphyses is present. Image in a patient with diastrophic dysplasia. The acetabulum is shallow and shows a double-hump configuration on the right side. Both the femoral heads are severely dysplastic.
  • Excessive valgus is present in the knee joint, with a mean tibiofemoral angle of 14°. Most patients experience some instability in early life. Signs of early degeneration and deformation of the bony epiphyses develop in patients younger than 6 years. The lateral femoral condyle is hypoplastic. The patellofemoral joint is abnormal with a marked patella infera, and the patella is in a lateral position with bony fragmentation. See image below. Image in a patient with diastrophic dysplasia. The patella is subluxed laterally, with mild hypoplasia of the lateral femoral condyle.
  • Characteristic radiologic features of the hands, as seen in the images below, and feet exist. The carpal centers appear early, in contrast to the epiphyseal delay observed elsewhere, and opaque borders and osteopenic centers, as well as some irregularity of shape, are depicted. The tubular bones of the hands are short, broad, and irregularly ossified, with metaphyseal flaring associated with flat epiphyses. The first metacarpal is particularly short, ovoid, or triangular, and the proximal phalanx of the thumb may be subluxated or dislocated. Although the proximal interphalangeal joints of the digits are ankylosed, a radiolucent space is present early on; this later fuses. Image in a patient with diastrophic dysplasia. The tubular bones of the hand are short and broad. The first metacarpal is particularly shortened. The ulna is shorter, and the radius shows flaring at its distal end. Image in a patient with diastrophic dysplasia. Oblique view of the hand shows a short first ray with marked abduction. Image in a patient with diastrophic dysplasia. Radiograph of the hands shows abducted and short first metatarsal, along with affection of the proximal interphalangeal (PIP) joint of all fingers. Ankylosis of the fifth PIP joint is present. The middle phalanges appear extremely short.
  • The tubular bones of the feet are similar to those of the hands, and metatarsus adductus with medial twisting of metatarsals is evident, as seen in the first image below. The first metatarsal may be particularly shortened. Equinus deformity is usually present, as seen in the last two images below. Image in a patient with diastrophic dysplasia. The metatarsus adductus with medial twisting of metatarsals is evident. The first metatarsal is shortened. Also note the lateral subluxation of the navicular over the talus that gives the appearance of a skew foot. Deformity of the foot in a patient with diastrophic dysplasia. Severe equinus deformity in a patient with diastrophic dysplasia.
• MRI: MRI studies may be helpful in the evaluation of patients with diastrophic dysplasia.^{[18, 25, 26]}

  • In cervical kyphosis with neurologic deficit, MRI performed in neutral position and in extension helps determine the degree of anterior cord compression. In all age groups, degenerative changes in the intervertebral disks and decreases in disk heights are common. No stenosis of the foramen magnum is present, but the spinal canal is narrowed, especially with advanced age. These findings also explain the stiffness of the cervical spine on clinical examination.
  • In a study of MRI analysis for the thoracic and lumbar spine, the transverse dural tube area at all levels was below the reference range. All patients had narrowed disk heights and a decrease in signal intensity on T2-weighted images, suggesting disk degeneration. All patients had muscular atrophy of psoas muscles and back muscles on T1-weighted images and degeneration-like facet joint hypertrophy.
  • MRI of the hip joint can depict the flattened femoral ossific nuclei, acetabuli, thickness of articular cartilage, and joint congruity.
• Ultrasonography: Plain radiographs do not provide adequate information in patients with diastrophic dysplasia, due to abnormal ossification and severe deformation. In one study, ultrasonography of the knee joint revealed lateral deviation of the anatomic complex of the femoral condyles and patella, deformed patellofemoral joint, hypoplastic lateral femoral condyle, deep trochlear groove, and a distally aligned patella or patella infera.^{[27, 28]}
• Prenatal ultrasonography: Prenatal ultrasonography may be used to diagnose this condition in utero during the second trimester. Long bone measurements at least 3 standard deviations below reference ranges, and abnormalities of feet and hands may be diagnostic. Parents may opt to terminate the pregnancy after genetic counseling.^{[29, 30, 31]}
• Arthrography: Arthrograms of major joints depict flattening of the epiphyses and other joint abnormalities.
• CT: CT scanning with or without 3-dimensional (3D) reconstruction may be useful in preoperative planning and for improving the definition of bony anatomy in cases of severe deformities. Image in a patient with diastrophic dysplasia. CT scan, A 3-dimensional reconstruction, shows bilateral dysplasia and dislocation of hips.

• DNA analysis: Prenatal diagnosis is possible in the first trimester via mutation analysis of chorionic villus DNA.
• Spirometry: Rigid spinal deformities can reduce the mobility of the chest cage. In one study, at least 1 abnormally low spirometric finding was found in 33% of children and in 54% of adults. The angle of thoracic or thoracolumbar scoliosis and the age of the patient is correlated with the measured parameters.

The histologic characteristics of the cartilage appear to be similar in the fetus and older patient and therefore may be useful in differentiating diastrophic dysplasia from other osteochondrodysplasias in the second trimester.

The degenerative changes are primarily seen in the resting cartilage. At low magnification, the changes appear as irregular myxoid degeneration with small cystic areas. At higher magnification, the chondrocytes are surrounded by a halo of dense-appearing cartilage matrix. The chondrocytic nuclei are larger than normal, with some lacunae containing 2 nuclei. The chondrocytes appear to be irregularly distributed in the surrounding densely staining matrix. Scattered foci are acellular, and within these foci, residual thickened collagen fibers form an irregular lacy pattern within amorphous material. The physeal growth zones have normal-appearing hypertrophic and proliferating zones with normal columnization.