Achondroplasia Workup

Updated: May 11, 2020
  • Author: Shital Parikh, MD; Chief Editor: Jeffrey D Thomson, MD  more...
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Workup

Laboratory Studies

Plasma can be analyzed for the FGFR3 mutation in the mother when a short-limb skeletal dysplasia is diagnosed antenatally by means of ultrasonography (US). [20, 10] This can be confirmatory for achondroplasia and can help the family to make educated decisions.

DNA testing can be performed when both of the parents are affected. Infants with affected genes from both the parents (double homozygous) are either stillborn or die shortly after birth.

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Imaging Studies

Radiography

Radiographs of the skull, spine, and extremities reveal the characteristic features. A lateral skull radiograph demonstrates midface hypoplasia, enlarged calvaria, frontal prominence, and shortening of the base of the skull. The size of the foramen magnum is diminished. (See the image below.)

Characteristic skull seen in patients with achondr Characteristic skull seen in patients with achondroplasia, with frontal bossing, small foramen magnum, midface hypoplasia, and relative enlargement of skull as compared with face.

A lumbar spine (anteroposterior [AP]) view reveals distinct narrowing on the interpedicular distances from proximal to distal in L1-5 (see the image below). Normally, the interpedicular distance from the cephalocaudad direction should increase. However, if this distance decreases or remains unchanged, it is abnormal. The changes should be observed in three consecutive vertebrae.

Progressive narrowing of coronal interpedicular di Progressive narrowing of coronal interpedicular distance in lumbar spine in patients with achondroplasia. Note characteristic shape of pelvis with horizontal sacral position.

The lateral view reveals shortening of the pedicles and vertebral bodies with significant posterior scalloping. Various degrees of thoracolumbar kyphosis may be present before walking age (see the image below). This may be associated with wedging of T12 or L1. Once ambulation is established, kyphosis generally improves, and lumbar lordosis develops. The inclination of the sacrum becomes increasingly horizontal.

Thoracolumbar kyphosis with narrow lumbar spinal c Thoracolumbar kyphosis with narrow lumbar spinal canal and concave posterior bodies in 13-month-old child with achondroplasia.

Scoliosis of more than 20° develops in some patients. The curves are relatively short and are located in the thoracolumbar or lumbar region. Rotation is not a prominent feature. Degenerative changes can be seen in the vertebral column, particularly at the anterior margins of the vertebral bodies located in the thoracolumbar area and in the cervical spine. However, such changes are compatible with the patient's age.

The pelvis is typically broad and short, and the ilium has a square appearance. The sacrosciatic notch is short, and the acetabular roof is horizontal (see the image below). The femoral neck is short with trochanteric overgrowth, giving an appearance of coxa vara. However, true coxa vara is not seen. Arthritic changes of the hip, even in older patients, usually are not observed. This can be attributed to the reduction of major joint lever arms and the comparative lightness (50 kg) of the patient.

Typical features of lower limbs in person with ach Typical features of lower limbs in person with achondroplasia, including horizontal acetabular roofs, small sacrosciatic notches, genu varum and ankle varum with relative overgrowth of fibula, and inverted V-shaped distal femoral physis.

The long bones have metaphyseal flaring and are short and thick. During the first year, the proximal metaphyses of the femur and the humerus have oval areas of radiolucency. Sites of major muscle attachments (eg, deltoid and patellar tendon tuberosity) are prominent.

The distal femoral physes are configured in the shape of an inverted V (chevron). Bowing usually affects the tibia more than the femur. The fibula is typically longer than the tibia.

The humerus is markedly shortened, and the radial head frequently is dislocated. The ulna is typically short with an elongated styloid process. The proximal and middle phalanges of the hand are broader, with greater shortening than the distal phalanges and metacarpals.

Primary radiographic criteria for diagnosis are as follows:

  • Decrease in interpedicular distance in the lumbar spine
  • Square short ilia
  • Short, broad neck of femur
  • Shortening of long tubular bones, with metaphyseal flaring
  • Brachydactyly

Secondary radiographic criteria for diagnosis are as follows:

  • AP shortening of lumbar pedicles
  • Dorsal concavity of lumbar vertebra
  • Long distal fibula
  • Short distal ulna
  • Long ulnar styloid

Computed tomography

The size of the foramen magnum can be measured most accurately by means of computed tomography (CT). [23, 24] The spinal canal is narrowed developmentally, particularly in the lower lumbar segments. The cross-sectional anatomy can be evaluated noninvasively with this modality. CT can be performed to develop a three-dimensional image of the rib cage, which can be used to calculate lung volumes and can substantiate a successful surgical chest expansion.

Magnetic resonance imaging

Given the incidence and potential severity of neurologic symptoms associated with foramen magnum stenosis, baseline magnetic resonance imaging (MRI) is strongly recommended in infancy. [25] Cervicomedullary compression at the foramen magnum, fusion of C1, or isolated subaxial cervical stenosis can be demonstrated (see the image below). In addition, MRI can show myelomalacia, intramedullary cyst, or angulation at the craniocervical junction.

MRI showing cervicomedullary compression at forame MRI showing cervicomedullary compression at foramen magnum in patient with achondroplasia.

MRI may be used to establish the cause of neurocranial enlargement. Dilated ventricles without hydrocephalus, and communicating and noncommunicating forms of hydrocephalus may be observed.

MRI is also recommended for preoperative evaluation of lumbar spinal stenosis, especially to determine whether associated disc herniations exist and the proximal level of compression. The average area of L1 is decreased by 39%, and that of L5 is decreased by 27%. Kyphosis correlates strongly with neurologic symptoms, and MRI can demonstrate apical wedging and neurologic involvement.

Ultrasonography

In the fetus, heterozygous achondroplasia is associated with normal or near-normal femur lengths until 20-24 weeks of pregnancy. Thereafter, the growth rate of the femur decreases. Hence, US may not be useful for diagnosing achondroplasia in the first half of the pregnancy. Later in the pregnancy, US can detect short-limb dysplasia. However, differentiation among various skeletal dysplasias is difficult.

In the neonate, US can be used to detect ventricle size and other abnormalities. It cannot be used once the sutures and fontanelles close. MRI is the imaging modality of choice at that time.

Cine-phase contrast and magnetic resonance angiography

Cine-phase contrast and magnetic resonance angiography (MRA) [26]  are useful for studying the pathophysiology of brainstem compression and hydrocephalus. Gated cine-phase contrast cerebrospinal fluid (CSF) flow studies can be used to evaluate CSF dynamics across the foramen magnum. MRA (venography) can be used to depict obstructed venous drainage due to jugular foramen stenosis. [27]  Steno-occlusive disease of the internal jugular vein, reduced blood flow in the superior sagittal sinus, and compensatory enlargement in the emissary veins can be depicted.

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Other Tests

Somatosensory evoked potential (SSEP) abnormalities have been reported for 44% of neurologically intact persons with achondroplasia and are probably related to brainstem compression at the level of the foramen magnum.

Pulmonary function tests are useful for preoperative evaluation when respiratory symptoms are present. Typically, the vital capacity is decreased, averaging 68% for affected males and 72% for affected females.

A sleep study may be performed if symptoms suggest airway obstruction. [28] The cause of airway obstruction can be established to guide the treatment. Differentiating between central sleep apnea (due to brain stem or upper cervical cord compression) and obstructive sleep apnea (due to midface hypoplasia) is helpful.

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Procedures

Reports exist of sudden blindness associated with an increase in the intracranial pressure (ICP). Hence, ICP monitoring is recommended in persons with achondroplasia with moderate ventriculomegaly, as demonstrated by MRI. This is performed with a percutaneous spinal catheter. Treatment is recommended when the ICP is higher than 15 mm Hg.

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Histologic Findings

Biopsy from the growth plates of the ilium and proximal fibula reveal an essentially normal structure. Glycosaminoglycan determination is normal. The proportion of proteoglycan aggregates increases in the fibular head. The defect is mainly quantitative and lies in the proliferative zone of the growth plate.

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