An 8-year-old boy was seen by an orthopedic surgeon for evaluation of growth and developmental distur-bances. He admits to generalized muscle weakness, joint stiffness, and a waddling gait with compromised stability. Physical examination reveals coarse facial features, short trunk dwarfism, short neck, pectus carinatum, protuberant abdomen, and enlarged wrists and hands.
Prepared by
Troy Marlow, MD
and
Timothy Han, III, MS
from the Department of Radiology at the Medical University of
South Carolina, Charleston, SC.
CASE SUMMARY
An 8-year-old boy was seen by an orthopedic surgeon for
evaluation of growth and developmental distur-bances. He admits to
generalized mus-cle weakness, joint stiffness, and a waddling gait
with compromised stability. Physical examination reveals coarse
facial features, short trunk dwarfism, short neck, pectus
carinatum, protuberant abdomen, and enlarged wrists and hands. His
mental capacity was age appropriate. Urine screening for
mucopolysaccharides was positive. Fibroblast culture of a skin
biopsy showed reduced activity of
N-acetyl-galactosamine-6-sulfate-sulfatase.
DIAGNOSIS
Morquio's syndrome
IMAGING FINDINGS
Anteroposterior and lateral views of the lower thoracic spine
and lumbar spine reveal flattening and irregularity of the
vertebral bodies. Anterior beaking is demonstrated in the thoracic
vertebrae on the lateral projection (Figure 1). The pelvic and
abdominal films show flared ilia laterally with inferior
constriction (wine-glass shape) (Figure 2). Frontal view of the
femora reveal enlarged acetabular cavities with rough margins, and
there are poorly formed femoral epiphyses and widened femoral necks
with coxa valga (Figure 3). Atlantoaxial subluxation at rest can be
demon-strated by lateral view of the craniocervical junction
(Figure 4). These findings, along with the biochemical laboratory
results, help to distinguish Morquio's syndrome from
spondyloepiphyseal dysplasia, which shares similar spinal changes,
but is more frequently associated with coxa vara.
DISCUSSION
There are at least 12 types of inherited genetic disorders
dealing with specific lysosomal enzyme deficiencies. This
collective group of mucopoly-saccharidoses (MPS) are associated
with an incomplete metabolism of keratan sulfate, dermatan sulfate,
heparan sulfate, or chondroitan sulfate within the lysosomes, with
the resultant accumulation in the brain, viscera, and joints
throughout the body.
2
Morquio's syndrome (MPS type IV) is the most common of these
storage disorders and is characterized by the inability to
metabolize keratan sulfate. This disease is autosomal recessive and
both sexes are affected with the same frequency. The predominant
clinical features of Morquio's syndrome are skeletal and
neurologic. Both types of Morquio's syndrome are characterized by
short-trunk dwarfism, fine corneal deposits, a skeletal dysplasia
that is distinct from other mucopolysaccharidoses, and preservation
of intelligence.
Children with Morquio's syndrome manifest short-trunk dwarfism
within the first 2 years of life. Marked dwarfism, dorsal
kyphoscoliosis, muscular hypotonia, and weakness are prominent
early childhood presentations. Also seen are coarse faces with
short nose, broad mouth, widely spaced teeth with thinned enamel,
corneal clouding, ligamentous laxity, and joint stiffness. Adult
height rarely exceeds 4 feet. Pectus carinatum (horizontal and
protuberant sternum) and a shortened neck with the head appearing
sunken into the chest are the norm. Mental capacity is generally
normal, but deafness often develops. Most patients survive into
their third or fourth decades.
1
Radiographic features include oval-shaped vertebral bodies with
anterior beaking (Figure 1); unossified femoral heads with proximal
femoral valgus deformities (Figure 3); and broad, flat ilia (Figure
2). By 2 to 3 years of age, universal platyspondyly with central
beaking is almost pathognomonic. The long tubular bones are
thickened and shortened as well.
1
Odontoid hypoplasia is common in children with Morquio's
syndrome. Instability of the odontoid process and ligamentous
laxity can result in life-threatening atlantoaxial subluxation
(Figure 4).
5
Atlantoaxial instability with progressive myelopathy is one of the
most disabling features of Morquio's syndrome. Neurologic injury
and sudden death are likely the result of spinal cord compromise
from C1C2 instability as well as extradural soft-tissue
hypertrophy anterior to the spinal cord in the upper cervical
spine.
2
The diagnosis is made by urine screening for MPS and confirmed
by serum testing for the specific sugar abnormalities or the
decreased enzyme activity of
N-acetyl-galactosamine-6-sulfate-sulfatase within leukocytes or
fibroblast cultures from skin biopsy upon laboratory assay.
2