Skeletal Dysplasias and Selected Chromosomal Disorders

Step I: Assessment of Disproportion

Micromelia is overall shortening of the extremities. Rhizomelia is relative shortening of the femurs and humeri. Mesomelia is relative shortening of the radii, ulnae, tibiae, and fibulae. Acromelia is relative shortening of the bones of hands and feet.

Classification of the shortened appendicular segment is helpful for diagnosis. Rhizomelia may be very helpful to confirm the specific diagnosis of the rhizomelic form of chondrodysplasia punctata. Very significant mesomelia suggests a group of specific disorders loosely classified as the mesomelic dysplasias. Acromelia is found in many disorders; when it occurs by itself, several specific dysplasias are suggested, including acrodysostosis, acromicric dysplasia, or pseudohypoparathyroidism.

The pattern of brachydactyly may facilitate diagnosis. For instance, brachydactyly type E manifests with variable shortening of the metacarpals and distal phalanges, and brachydactyly type A4 manifests with shortening restricted to the second and fifth middle phalanges. Even the absence of acromelia may be helpful. The lack of significant hand and foot shortening is a significant feature of spondyloepiphyseal dysplasia congenita (SEDC), a type 2 collagenopathy.

Step II: Assessment of Epiphyseal Ossification

If epiphyseal ossification is delayed or if the ossified epiphyses are very small, irregular for age, or both, then an epiphyseal dysplasia of some sort is present. Carpal and tarsal bones are often affected. In diseases that can be considered pure epiphyseal dysplasias such as multiple epiphyseal dysplasia (MED) and pseudoachondroplasia, carpal and the tarsal bones are markedly crenellated and small ( Fig. 132.1 ). Another excellent location for epiphyseal analysis is the ring apophyses of the vertebral bodies, which exhibit delayed and irregular epiphyseal ossification in epiphyseal dysplasia. Central anterior vertebral body protrusions (central tongues or beaking) noted in Morquio syndrome and pseudoachondroplasia are also disorders related to abnormalities of the ring apophyses.

Step III: Assessment of Metaphyses and Physes

Fraying and irregularity of the physes and abnormal flaring of the metaphyses indicate disturbed endochondral ossification. Marked irregularity of the physes is characteristic of the pure metaphyseal dysplasias such as metaphyseal dysplasia, Jansen or Schmid type. When the metaphyses are merely flared and the physes are fairly normal, endochondral ossification may be slowed, but the actual process of endochondral ossification progresses normally. This occurs in achondroplasia. The metaphyses are flared, whereas the physis and the zone of provisional calcification (ZPC) are sharply defined ( Fig. 132.2 ).

Rickets also disturbs the physis. In rickets, physeal abnormalities lead to the classic appearance of metaphyseal cupping and fraying. Except in healing rickets, the ZPC is inapparent. In metaphyseal chondrodysplasias, the ZPC is present, although it is markedly irregular ( Fig. 132.3 ). Analysis of the sclerotic line of the ZPC is frequently an excellent differentiating feature. Other factors include prominent osteopenia in rickets with blurring of the trabeculae; clinical data are also very helpful.

Step IV: Assessment of the Diaphyses

Diaphyseal abnormalities primarily include bent bones and thickened sclerotic bones. The classic bent bone dysplasia is campomelic dysplasia. Others include hypophosphatasia and kyphomelic dysplasia. Thickened and sclerotic diaphyseal cortices may indicate one of the craniotubular dysplasias.

Step V: Analysis of the Vertebral Bodies

Decreased height of the vertebral bodies is termed platyspondyly . The lumbar vertebral bodies are the best level to analyze compared with the cervical level, especially in infancy. The cervical vertebral bodies tend to appear relatively hypoplastic compared with other levels in the normal infant. This is because ossification occurs later in cervical vertebral bodies compared with vertebral bodies elsewhere. In addition to platyspondyly, other vertebral body changes are important. In the lumbar spine in normal children, the interpediculate distance usually widens on a frontal film moving inferiorly. Inferior narrowing of the interpediculate distance is a feature of fibroblast growth factor receptor 3 (FGFR3) abnormalities such achondroplasia and thanatophoria.

Anisospondyly is when the vertebral body shape varies wildly ( e-Fig. 132.4 ). Multiple ossification centers may also be present. Although rare, this is a specific finding in dyssegmental dysplasia.

Step VI: Assessment of Bone Mineralization

Bone mineral density should be assessed by not only examining the actual “whiteness” of bones but also by determining the relative thickness of the cortices relative to the medullary cavity and the coarseness of the trabeculae. Osteopenia, especially when severe, indicates defective bone mineralization, as seen in rickets, hypophosphatasia, and osteogenesis imperfecta (OI). Abnormally dense bones may indicate one of the craniotubular disorders such as pyknodysostosis and osteopetrosis. In the neonate, bones are normally sclerotic and the medullary cavity narrowed. Distinguishing abnormally dense bones from normal neonatal sclerosis can be difficult.

Step VII: Assessment of Joints

Multiple joint dislocations are a salient and persistent feature of some dysplasias. A standard skeletal survey frequently includes only frontal views of the skeleton, which may make it difficult to identify joint dislocations, especially in the infant. The elbow is frequently involved in the setting of dislocations secondary to a dysplasia. Dedicated lateral views are recommended when dislocation is clinically suspected.

Step VIII: Summation

After all radiologic findings have been established, a gamut search of some or all of these abnormalities, in conjunction with the clinical findings, may lead to the specific diagnosis. If the “group” of dysplasias has been established, then the specific diagnosis can often be made by referring to a differential diagnosis table such as that developed by Taybi and Lachman.

Fibroblast Growth Factor Receptor Type 3 Group

Common Features in FGFR3 Group

• Platyspondyly

• Narrow sacrosciatic notch

• Interpediculate narrowing

• Short, thick long bones

• Ovoid lucency at femoral necks (scooped out appearance)

• Frontal bossing

• Trident hands

• Fibula longer than tibia

Thanatophoric Dwarfism

Given the lethality of this dysplasia, it is aptly named after Thanatos, the Greek god of death ( Thanatophoria , meaning “death loving”).

Type 1 includes “cloverleaf skull,” caused by in utero craniosynostosis, and curved long bones. The femurs have a “French telephone receiver” appearance. The type 2 variant has straight long bones and no craniosynostosis.

Platyspondyly is severe. The vertebral bodies are described as U -shaped or H -shaped on an anteroposterior projection.

Radiographic Findings ( Fig. 132.5 )

• 1.

  Skull: proportionately large skull in relation to the body, narrow skull base, cloverleaf skull (type 1 only)

• 2.

  Thorax: long, narrow trunk; very short ribs; handlebar clavicles

• 3.

  Spine: severely flattened, small vertebral bodies with round anterior ends

• 4.

  Pelvis: small, flared iliac bones; very narrow sacrosciatic notches; flat, dysplastic acetabula

• 5.

  Extremities: generalized micromelia; ovoid lucency of femoral necks, round proximal femoral metaphyses with medial spike, curved long bones (type 1 only)

Achondroplasia

Patients with achondroplasia have normal mentation and a normal or near normal lifespan. As in other members of the FGFR3 family, long bones are short and thick. Interpediculate narrowing is present. In infancy, femoral necks have a scooped out appearance. Since the sacrosciatic notches are narrowed, the pelvic inlet has an appearance of a wide-mouthed champagne glass.

Except for the portions of the occipital bone that form the margin of the foramen magnum, all the bones of the skull are formed by membranous ossification. This results in an enlarged forehead and is termed frontal bossing . In contrast, the foramen magnum is narrowed and can cause cervicomedullary compression.

Radiologic Findings ( Fig. 132.6 and e-Fig. 132.7 )

• 1.

  Skull: enlarged, with significant midface hypoplasia; hydrocephalus rarely present; small skull base with tight foramen magnum

• 2.

  Thorax: small; shortened and anteriorly splayed ribs

• 3.

  Spine: short pedicles with decreased interpediculate distance most marked in the lumbar spine moving downward; posterior vertebral body scalloping, gibbus deformity

• 4.

  Pelvis: round iliac wings with lack of flaring (elephant ear–shaped), flattened acetabular roofs, narrow sacrosciatic notches with champagne glass shaped pelvic inlet

• 5.

  Extremities: rhizomelic micromelia

• 6.

  Hands: brachydactyly with trident hands

• 7.

  Knees: central deep notch in growth plates (Chevron deformity)

• 8.

  Hips: proximal femoral ovoid lucency (infancy); hemispheric capital femoral epiphyses, short femoral necks

• 9.

  Legs: prominent tibial tubercle apophyseal region, fibula overgrowth

• 10.

  Arms: Cortical hyperostosis at deltoid insertion on anterolateral humerus

Hypochondroplasia

In hypochondroplasia, radiographic and clinical findings are less severe compared with achondroplasia, and the diagnosis can be challenging. Stature is slightly shortened but is highly variable and may be normal given the range of normal stature in society. Radiographically, aside from shortening of the long bones, interpediculate narrowing is the most sensitive finding.

Common Features in Type 2 Collagenopathy Group

• Platyspondyly

• Delay in epiphyseal ossification most apparent in femoral heads

• Cleft palate

• Myopia

• Short stature

• Occipitoatlantal or atlantodental instability

Spondyloepiphyseal Dysplasia Congenita

The combination of platyspondyly and short long bones make SEDC a good example of short-limbed, short-trunk dwarfism. It is also a good model for an epiphyseal dysplasia. Ossification in the vertebral bodies begins in the fetus at the lower thoracic spine and progresses superiorly and inferiorly. The cervical spine ossifies last. The normal cervical spine vertebrae at birth are slightly dorsally wedged and are small. In infants with SEDC, the cervical vertebral bodies show little or no ossification. Thoracic and lumbar bodies are, however, small, dorsally wedged, and anteriorly rounded (pear- or oval-shaped), similar in appearance to the cervical spine in the normal infant. In childhood, characteristic central beaks, typical of epiphyseal delay, may be seen. In the adult, vertebral bodies are flattened with irregular end plates.

At birth, no ossification of the talus, calcaneus, or the epiphyses at the knee is present. Normally, the talus and the calcaneus ossify at 20 to 24 weeks' gestation and the epiphyses at about 36 weeks' gestation.

One salient feature is that the hands and feet in patients with SEDC are normal, apart from carpal, midfoot, and hindfoot ossification delay.

Radiologic Findings ( Fig. 132.8 )

• 1.

  Thorax: small; short ribs

• 2.

  Spine: dorsally wedged or oval vertebral bodies (at birth); anteriorly rounded platyspondyly (later)

• 3.

  Pelvis: absent pubic ossification (at birth and during infancy), vertical ischia with short ilia

• 4.

  Extremities: normal tubulization with mild micromelia, significant generalized ossification delay (early), and hypoplastic-appearing or dysplastic epiphyses (later), unossified talus or calcaneus in the newborn, normal hands and feet with ossification delay (epiphyses or carpal, tarsal)

Kniest Dysplasia

The same delay in epiphyseal ossification is seen along with platyspondyly. Cloudlike dystrophic calcification is present in abnormally enlarged epiphyses as the child gets older. On magnetic resonance imaging (MRI), the areas of calcification have prolonged T2 values that are likely related to the degeneration of abnormal collagen matrix.

Radiologic Findings ( e-Fig. 132.9 )

• 1.

  Thorax: small to normal

• 2.

  Spine: coronal clefts (at birth and during infancy), platyspondyly with endplate irregularity (later)

• 3.

  Extremities: dumbbell femurs; generalized ossification delay, epiphyses becoming hypoplastic or dysplastic and then later even mega-epiphyses, cloudlike irregular calcification in physeal plate regions (in late childhood and early adulthood); hands with bulbous joints (metaphyseal flaring or epiphyseal fragmentation) mimicking rheumatoid arthritis

Note: In the newborn, Kniest syndrome is radiographically identical to SEDC except for coronal clefts and dumbbell femurs.

Common Features in Type 11 Collagenopathy Group

• Similar to type 2 collagenopathy

• Cleft palate

• Sensorineural hearing loss

• Myopia (except for Stickler type 3)

• Epiphyseal dysplasia (may be large or mildly flattened)

• Early arthritis

• Platyspondyly