Specific Disease Entities
Skeletal dysplasias are a very heterogeneous group of disorders with 461 different
disorders classified into 42 groups, based on genotypes and phenotypes.[[3]] Skeletal survey is an integral part of assessment of skeletal dysplasias.[[4]] While assessing spine radiograph as a part of skeletal survey, a systematic approach
is to be adopted.[[5]]After assessing whether it is a generalized/localized abnormality in the spine;
the spine radiograph should be assessed for the state of ossification, segmentation
anomaly, flattening (platyspondyly), or specific morphologic changes. Here in this
article, we will describe disease entities subcategorized depending on their bone
density. We shall highlight those diseases where spine radiograph is diagnostic; either
alone or in combination with a few other radiographs.
Diseases with uniform/generalized affection of the entire vertebral column
This category can be subdivided into three groups: diseases with normal, decreased,
and increased bone density. Individual groups are described separately.
Diseases with normal bone density
Achondroplasia
One of the commonest skeletal dysplasia in clinical practice; this disorder shows
some characteristic imaging findings. Spine radiograph alone can be suggestive; and
sometimes diagnostic of this disease entity. Classical imaging findings include progressive
narrowing of interpedicular distance in lumbar vertebrae, narrow pedicles causing
spinal canal stenosis, posterior scalloping of vertebral bodies, and “bullet vertebra”
at dorsolumbar junction [[Figure 2]].[[6]] Other findings include an exaggerated lumbar lordosis and horizontally oriented
sacrum. Other radiographs may show classical findings as well [[Table 1]].
Figure 2 (A-C): (A-C) Achondroplasia. (A) Lack of progressive widening of interpedicular distance,
with narrowing at L5-S1 level (arrow). Lateral spine radiograph (B) shows posterior
scalloping (arrows) of vertebral bodies, narrow pedicles (dotted arrows), and classical
“bullet vertebra” appearance at the dorsolumbar junction. D12 has been marked for
diagrammatic depiction of morphology (yellow: vertebral body, blue: pedicle). Pelvis
radiograph (C) “tombstone pelvis”, trident sign (arrow), and rhizomelic shortening
Table 1
Common imaging findings in skeletal dysplasias where spine radiograph is suggestive/diagnostic
|
Disease entity
|
Changes in spine
|
Other radiographs
|
|
Achondroplasia
|
Progressive narrowing of interpedicular distance in lumbar vertebrae
Posterior scalloping of vertebral bodies ‘bullet vertebrae’
Exaggerated lumbar lordosis
Preserved bone density and vertebral body height
|
Rhizomelic dwarfism
Short, broad ‘champagne glass’ pelvis with round, broad ‘elephant ear’ iliac wings
‘Trident sign’: prominent sciatic notch
Chevron deformity, especially at lower femoral metaphysis
Widely spaced 2nd and 3rd metacarpals (‘trident hand’)
|
|
Thanatophoric dysplasia
|
Wafer thin vertebral bodies
Normal bone density
|
Micromelic dwarfism with bowed (type 1) or straight (type 2) femurs & brachydactyly
Macrocephalic clover leaf skull
Narrow thorax with short ribs
|
|
Pseudoachondroplasia
|
Platyspondyly
Wide central anterior tongue like projection
|
Delayed fusion of triradiate cartilage in pelvis
Very delayed appearance and development of femoral head epiphyses
Epimetaphyseal involvement
Prominent posterior costochondral junctions
|
|
MPS IV (Morquio syndrome)
|
Variable platyspondyly
Increased intervertebral disc height
Thin anterior central beaking
Odontoid hypoplasia
|
Macrocephaly
Delayed carpal/tarsal and femoral head ossification with premature arthropathy
Proximal pointing of metacarpals
Irregular epiphyses with widened metaphyses
|
|
Spondyloepiphyseal dysplasia congenita (SEDC)
|
Significant platyspondyly
Anisospondyly
Cervical kyphosis
Pear shaped vertebral bodies
|
Delayed ossification of carpals, tarsals including calcaneum, femoral head and pubic
bone with premature arthropathy
Macrocephaly
Horizontal acetabular roof
Normal hands/feet
Retinal detachment, high myopia
|
|
Spondyloepiphyseal dysplasia tarda (SEDT)
|
Variable platyspondyly
Posterior hump of vertebral bodies
|
Normal skull/hands/feet
Premature arthropathy of hips with irregular epiphyses
Narrow pelvis
|
|
Progressive pseudorheumatoid arthropathy of childhood (PPAC)
|
Mild platyspondyly
Reduced intervertebral disc height
Gouge shaped anterosuperior vertebral endplate defect
|
Metaphyseal expansion in short bones of hand and feet, especially the proximal phalanges
|
|
Spondylometaphyseal dysplasias (SMD)
|
Subtle vertebral endplate irregularities
Mild (Sutcliffe type) to pronounced platyspondyly (Kozlowski type)
Ovoid vertebral bodies (Sutcliffe type)
Rounded pedicles (Kozlowski type)
|
Metaphyseal corner fracture of long bones (Sutcliffe type)
|
|
DMC syndrome
|
Irregular constrictions at central vertebral endplates
|
Short stature, intellectual disability
Lacy iliac wings
Small & irregular femoral head epiphyses
|
|
Chondrodysplasia punctata (CDP)
|
Vertebral body stippling
Coronal clefting in dorsolumbar vertebrae
|
Variable stippling of multiple epiphyses of long bones, carpals and tarsals (early
in life)
Irregular epiphyses with asymmetric limb shortening (late in life)
|
|
Osteogenesis imperfecta
|
Reduced bone density
Biconcave codfish vertebrae
Mild to severe platyspondyly (type 3) with multiple vertebral body collapses (type
3)
|
Diffuse osteopenia
Pencil thin cortices
Multiple long bone metaphyseal fractures at variable stages of healing
Macrocephaly with platybasia and Wormian bones
Hypertrophic Callus (type 5)
Interosseous membrane ossification (type 5)
|
|
Achondrogenesis
|
Poor ossification of vertebral bodies with preserved ossification of pedicles
Platyspondyly
Widened cervical and lumbar spinal canals (type 1B)
|
Micromelic dwarfism
Unossified skull vault (type 1A/B)
Crescent shaped iliac wings (type 1A/B)
Beaded ribs (type 1A)
|
|
Hypophosphatasia
|
Poor ossification of both vertebral bodies and pedicles
|
Poor skull base ossification
Thin ribs
Metaphyseal lucencies
Diaphyseal spurs
Missing long bones (absent ossification)
Hypoplastic fibulae
|
|
Osteopetrosis
|
Increased bone density with predominant endplate involvement (‘sandwich vertebrae’)
|
Obliteration of medullary cavities of long bones
Bone within bone appearance
Multiple long bone fractures
|
|
Pyknodysostosis
|
Spool shaped vertebrae (central concavity at anterior border)
|
Obtuse mandibular angle
Wide open skull sutures with multiple wormian bones
Terminal acrosteolysis
Preserved medullary cavity
Small pelvis with shallow acetabular cavity
|
Hypochondroplasia
The clinical phenotype and radiological findings are similar to achondroplasia; but
findings are usually mild. Spine and cranial radiographs may show only mild changes
[[Figure 3]].[[7]]
Figure 3 (A and B): (A and B) Hypochondroplasia: AP radiograph of (A) showing only mild progressive narrowing
of interpedicular distance. Lateral radiograph (B) shows definite, but mild, posterior
vertebral body scalloping (arrows)
Thanatophoric dysplasia
This is a lethal skeletal dysplasia, allelic to achondroplasia but having more severe
presentation. It can be detected on prenatal ultrasonography in view of severe micromelia.
Typical radiographic findings [[Figure 4]] include “wafer-thin” vertebral bodies, bent or “ telephone handle” shaped femur,
trident pelvis, severe micromelia, and a deformed “cloverleaf”skull in some subtypes.[[5]] The bone density is usually normal.
Figure 4: Thanatophoric dysplasia in a stillborn. Note well mineralized bones, “wafer thin”
vertebrae (arrows), trident acetabulum (dotted arrow & marked in yellow), and short
bowed femur (curved arrows)
Campomelic dysplasia
This is a perinatally lethal dysplasia. Common imaging findings include shortening
and bowing of the long bones, diaphyseal spurs, hypoplastic scapulae, narrow and “foreshortened”
iliac wings, 11 pairs of ribs, and hypoplastic fibulae. The long bones in lower limb
shows typical angulation; in femur at the junction of upper third and mid-third; whereas
in tibia at the junction of mid and lower third.
In the spine radiograph, the typical imaging finding is absent ossification of the
pedicles of thoracic vertebrae.[[8]] Bone density is usually normal.
Pseudoachondroplasia
This disease entity is a variant of the spondyloepiphyseal dysplasia group of disorders.
Spine as well as the epiphyses show typical imaging features. Spine radiograph reveals
platyspondyly and classical central “tongue-like” projection, most prominent in the
lumbar vertebrae [[Figure 5]].[[9]] This is to be differentiated from the central beaking of Morquio syndrome. The
projection in pseudoachondroplasia is thicker/wider than that in Morquio syndrome.
Other important findings in pseudoachondroplasia include prominent posterior costo-vertebral
junctions, generalized epiphyseal irregularity, delayed appearance, and small size
of femoral head epiphysis, wide open triradiate cartilage, metaphyseal beaking/spurs[[Figure 6]].[[9], [10]]
Figure 5 (A and B): (A and B) Pseudoachondroplasia. Spine radiograph in two patients. 2 year old girl
(A) showing severe platyspondyly with anterior tongue-like projections (arrows); mimicking
MPS IV. Seven year old girl showing more pronounced projections (arrows in B). L1
vertebral body has been marked in yellow for diagrammatic representation of morphology
Figure 6 (A and B): (A and B) Classical appearance of pelvis in pseudoachondroplasia in different age
groups. 6 year old girl (A) showing wide unossified Y cartilage (asterisk), small
femoral head epiphyses (arrow), unossified inferior pubic rami (block arrows). Same
girl at the age of 13 years (B) show more pronounced degenerative changes around hip
joints. Note that the femoral head is yet very small (arrow); Y cartilage and inferior
pubic rami (block arrow) still unossified. Note the typical flaring of lower femur
and upper tibial metaphyses (marked in yellow)
Mucopolysaccharidoses (MPS)
Mostly diagnosed on the clinical phenotype and enzyme assays, this group of disorders
shows typical changes in spine radiograph; as a part of “dysostosis multiplex.” Usual
imaging findings include variable platyspondyly, anterior vertebral beaking, odontoid
hypoplasia, and maintained/increased intervertebral disc height [[Figure 7]].[[11]] The beaking is in anteroinferior location in MPS type 1 (Hurler’s syndrome)[[12]] and central in MPS type 4 (Morquio syndrome).[[13]] Other imaging findings are listed in [[Table 1]].
Figure 7 (A-C): (A-C) MPS 1 (A) showing typical anteroinferior beaking of lumbar vertebrae (arrows).
MPS 4 (B) showing diffuse platyspondyly with thin central beaking (arrows) and widened
IV disc spaces. Typical vertebral shape has been marked in yellow in a and blue in
b. Hand radiograph (C) showing proximal pointing of metacarpals (marked in yellow)
and “bullet shaped” phalanges (marked in white)
Mucolipidosis (MLS)
Several subtypes of this disease entity exists. Skeletal survey reveals imaging findings
similar to MPS; with the additional finding of periosteal “cloaking”[[14]] or lamellated periosteal reaction involving the long bones [[Figure 8]]. This typical imaging finding is most evident in infancy and disappears thereafter.
Figure 8 (A-C): (A-C) Mucolipodosis in a 3 year old boy. Globular appearance of vertebrae with subtle
anteroinferior beaking (marked in yellow in A). Florid dysostosis multiplex is not
seen, however medullary expansion (manifested by thinning of cortices) and undertubulation
is evident in hand bones and humerus (arrows in B and C)
Spondyloepiphyseal dysplasia congenita (SEDC)
As evident by its name, this disease entity affects the spine and the long bone epiphyses.
A disease caused by faulty collagen development (collagenopathy)[[15]]; this disease usually manifests with a very short stature, coxa vara, waddling
gait, and retinal detachment/high myopia in childhood.[[16]] Radiographic findings are quite characteristic. Spine radiograph reveals significant
platyspondyly, anisospondyly (variation in size of vertebral bodies), cervical kyphosis,
and a pear-shaped vertebral body in smaller children/infants [[Figure 9]].[[17]] Other classical imaging findings include apparent pubic diastasis, coxa and vara,
very delayed appearance of femoral head epiphyses, generalized epiphyseal irregularity
[[Table 1]].
Figure 9 (A-D) : (A-D) Spondyloepiphyseal dysplasia congenita (SEDC). (A and B) Anisospondyly: L4
is larger than L3 and L5 (A); L5 smaller than rest of the lumbar vertebrae (B) Cervical
kyphosis (arrow) with cervical vertebral body hypoplasia (C) Apparent DDH in pelvis
radiograph (D) in a 4 year old boy due to delayed ossification of femoral head epiphyses
(dotted arrows)
Spondyloepiphyseal dysplasia tarda (SEDT)
A very heterogeneous group of disorders, this disease also affects the spine as well
as the epiphyses. However, the presentation is not as early as SEDC. Usual clinical
presentation is with premature osteoarthritis involving the large joints. Many clinical
variants are known to exist. Typical imaging findings include variable platyspondyly
and “posterior hump” of vertebral bodies [[Figure 10]].[[18]] Epiphyses of the long bones show irregular outline and early degenerative changes.
Figure 10 (A and B): (A and B) Spondyloepiphyseal dysplasia tarda (SEDT). Platyspondyly with classical
“hump” at the posterior 2/3rd part of vertebral bodies (arrows in A) with severe reduction of IVD spaces. Extensive
early degenerative changes around hip joints (arrows in B)
Progressive pseudorheumatoid arthropathy of childhood (PPAC)
A subtype of SEDT; this disease has a unique clinical presentation with early development
of painless joint contractures involving small joints of the hand.[[19]] It often mimics rheumatologic condition[[20]] and misdiagnosed based on clinical appearance alone. Imaging is diagnostic of this
entity. Spine radiograph shows anterosuperior endplate defect (gouge shaped) with
mild platyspondyly. Early development of degenerative changes and reduction of IVD
spaces may occur. Diagnostic hand/feet radiographic finding is metaphyseal expansion
of proximal phalanges [[Figure 11]].[[21]]
Figure 11 (A and B): (A and B) PPAC in a 10-year old boy presenting with painless contractures of small
joints of hands. Typical anterosuperior endplate defects (arrows) in dorsolumbar vertebrae
(A). Typical morphology marked in yellow. Classical metaphyseal expansion of the proximal
phalanges (arrows in B)
Spondylometaphyseal dysplasias (SMD)
Various subtypes exist; with the common feature of involvement of spine as well as
long bone metaphyses. The spinal changes may range from subtle endplate irregularity
to platyspondyly [[Figure 12]]. Spondylometaphyseal dysplasia Sutcliffe type (corner fracture type) may show ovoid
appearance of vertebral bodies. A distinctive feature of this entity is presence of
“corner fractures” at long bone metaphyses.[[22]] SMD Kozlowski type presents with a more pronounced platyspondyly and rounded appearance
of pedicles on AP spine radiograph.[[23]]
Figure 12 (A-C): (A-C) Spondylometaphyseal dysplasia Kozlowski type. Significant platyspondyly (arrows
in A and B) with rounded pedicles (dotted arrow in A). Extensive metaphyseal irregularity
(arrow) in proximal femur (C)
Multiple epiphyseal dysplasia (MED)
Multiple epiphyseal dysplasia primarily presents as generalized epiphyseal irregularity
and sclerosis.[[24]] The spinal changes are variable, and may be only subtle irregularity of the endplates.[[18]]
Dyggve-Melchior Claussen syndrome (DMC)
Clinical presentation of this rare disorder is usually with intellectual disability
and short stature. Apart from the classical and characteristic “lacy iliac wings”[[25]]; the spinal changes also are quite suggestive. It presents as irregular constrictions
at the central vertebral endplates [[Figure 13]].
Figure 13 (A and B): (A and B) DMC in a 7-year girl with intellectual disability. Typical central endplate
depression in thoracolumbar vertebrae (arrows in A). Typical morphology marked in
yellow. Classical “lacy” iliac wings (arrows in B)
Chondrodysplasia punctata (CDP)
Several subtypes of this disease exist. Most striking imaging appearance is stippling
of the bones.[[26]] This feature can be seen involving long bone epiphyses, carpal and tarsal bones
and even involving the vertebral bodies. Coronal clefts can be seen in dorsolumbar
vertebrae [[Figure 14]].[[18]] Platyspondyly is usually absent.
Figure 14: Chondrodysplasia punctata. Extensive stippling involving nearly all vertebral bodies
including sacrum (arrows)
Diseases with reduced bone density
Osteogenesis imperfecta (OI)
Phenotypically and genotypically very heterogeneous; this disease entity can present
either in the perinatal period or much later in life with recurrent fractures. The
most severe lethal perinatal type 2 OI may not very often undergo radiological imaging.
Type 3 OI shows the presence of significant platyspondyly; multiple vertebral body
collapses [[Figure 15]]; evidence of recurrent fractures involving long bones and ribs, multiple wormian
bones in the skull.[[1], [18]] Other subtypes may show a milder degree of platyspondyly. Other imaging findings
of OI are listed in [[Table 1]].
Figure 15 (A-C): (A-C) Osteogenesis imperfecta type 3. Note severe osteopenia and multiple vertebral
body collapses (arrows in B) (A and B). Note that owing to osteopenia, it is difficult
to differentiate between vertebral body and IV disc space density. Severely deformed
long bones with transverse fracture (arrow in C)
In a spine radiograph with generalized osteopenia and platyspondyly; it is always
prudent to exclude leukemia as a cause, especially in a recent onset platyspondyly.
Achondrogenesis
This is a lethal skeletal dysplasia. Several different subtypes have been described;
types IA, IB, and II. Their radiological phenotypes are different; and so also are
the genetic abnormalities. All the three types show absent/very poor ossification
of vertebral bodies with ossification of pedicles. Crescent shaped iliac wings and
non-ossified skull vault are seen in types IA and IB. Type IA also shows “beaded ribs.”
Type IB shows widening of cervical and lumbar spinal canals, termed as “cobra-head”
appearance [[Figure 16]].[[5], [27], [28]] It is important to recognize the findings of undermineralization and platyspondyly
on an antenatal sonography.
Figure 16: Achondrogenesis type IB. infantogram in a stillborn fetus shows non-ossified vertebral
bodies and visualization of the pedicles (arrows), crescent shaped iliac wing (dotted
arrow and marked in yellow), severe micromelia (curved arrows), no beading of the
ribs
Hypophosphatasia
Perinatal hypophosphatasia is a rare lethal skeletal dysplasia characterized by undermineralization
of bones. There is poor ossification of neural arches, pedicles, and even entire vertebral
bodies.[[29]] Other imaging findings include shortening and bowing of long bones with diaphyseal
“spurs”, metaphyseal lucencies, non-ossification involving long bones (missing bones),
hypoplastic fibulae, absent skull base ossification, and thin ribs.
Osteopenia with tall vertebral bodies in a child with short stature can be found in
3M syndrome.
Diseases with increased bone density
Osteopetrosis
One of the common sclerosing bone dysplasia; this disease presents with hepatosplenomegaly
and signs of bone marrow failure.[[1]] Osteopetrosis has two major types: autosomal recessive (more severe infantile variety)
and autosomal dominant variety.
The autosomal dominant variant has two subtypes: I and II. Commonly, the patients
present with recurrent fractures, hepatosplenomegaly, and anemia. Multiple cranial
nerve compression may occur secondary to skull vault sclerosis. Radiographic features
include generalized osteosclerosis, sclerosis of the base of skull (subtype I of autosomal
dominant osteopetrosis), multiple fractures involving the long bones.
Spine radiograph shows classical “sandwich” vertebrae, especially in the subtype II
autosomal dominant form.[[18], [30]] This appearance refers to a marked sclerosis of the upper and lower endplates [[Figure 17]]. Other long bones show the classical “bone-within-bone” appearance.
Figure 17 (A and B): (A and B) Osteopetrosis. Classical “sandwich vertebrae” (arrows in a). Extensive
bony sclerosis and obliteration of marrow cavity (asterisk in B). Note fracture of
left femoral neck (arrow in B)
The autosomal recessive variant of osteopetrosis has more severe clinical manifestations
early in infancy. They present with failure to thrive, hepatosplenomegaly, anemia
and pancytopenia, and features of cranial nerve entrapment. Radiographic features
include generalized osteosclerosis, obliteration of marrow cavity, bone-within-bone
appearance, and calvarial sclerosis. Renal tubular acidosis may be associated.
Pyknodysostosis
This is another sclerosing bone dysplasia and considered in a differential diagnosis
of osteopetrosis on radiographs. The clinical presentations are different from that
of osteopetrosis. Usually there is no hepatosplenomegaly or anemia.[[1]] On radiographs, medullary cavities of the long bones are preserved. Differentiation
from osteopetrosis solely on the basis of spinal radiograph is not often possible.
Typical imaging findings include “spool shaped” vertebrae,[[31]] acro-osteolysis of distal phalanges of hands/feet, obtuse mandibular angles, and
wide open cranial sutures [[Figure 18]].[[32]]
Figure 18 (A-C): (A and C) Pyknodysostosis. Osteosclerosis and spool shaped vertebrae (arrows in A,
and marked in yellow). Associated findings are obtuse mandibular angle (B), wide open
lambdoid suture (arrow in B) and acroosteolysis (dotted arrow in C)
Diseases with more focal/localized involvement of the vertebral column
This group predominantly involves the vertebral segmentation anomalies; which can
be isolated or as a part of some defined syndromes. Isolated segmentation anomalies
of one vertebral body in the form of a butterfly vertebra or hemivertebra may be an
isolated finding; however, in presence of specific clinical morphologic markers, they
may be significant.
Multiple vertebral segmentation anomaly is more suggestive of a syndromic association.
Klippel-Feil syndrome
Usually presents as a short neck, low hairline and restriction of neck movements.
On radiographs, there are usually multiple cervical vertebral segmentation anomalies,
an abnormal bony bar (omovertebral bar) connecting a high-up and small malaligned
scapula.
Spondylocostal dysostosis
This is a heterogeneous group of disorder characterized by multiple vertebral segmentation
anomalies (>/= 10), and associated rib anomalies (fusion/absence/malalignment). The
thoracic cavity is mostly symmetrical in these groups of disorders. The spondylocostal
dysostosis type 1 is also known as Jarcho-Levin syndrome and is characterized by severe
shortening of the axial skeleton resulting in a “crab-like chest.” The typical radiological
appearance of SCD type 1 is a “pebble like” appearance of the vertebral bodies; whereas
in SCD type 4 the classical appearance described is a “tramline” appearance [[Figure 19]] secondary to the prominent pedicles.[[33]]
Figure 19: Spondylocostal dysostosis 4. Multiple vertebral segmentation anomalies (arrows) and
associated rib anomalies (dotted arrow). Note the prominent pedicles giving rise to
“tram track appearance”. Lumbar vertebrae are normal
There are several diagnostic algorithms[[33]] described for analysis of vertebral segmentation anomalies, detailed description
of which is beyond the scope of this article.
