Dysostosis Multiplex

Ralph Lachman, MD
Cedar Sinai Skeletal Dysplasia Registry
Sean Turbeville, Ph.D.
BioMarin Pharmaceutical Inc.
Introduction
Spine
The mucopolysaccharidoses (MPS) have in common a quite specific radiological expression, which is termed “dysostosis
multiplex.” This poster presentation covers the entire skeletal system to show the spectrum of dysostosis multiplex changes
suggesting the presence of MPS disease in the individual. Also, several previously unreported dysostosis multiplex findings
are shown.
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Helen Nicely, Ph.D.
BioMarin Pharmaceutical Inc.
Superiorly notched [inferiorly beaked] vertebral bodies
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Middle beaked in MPS IV [Morquio]
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Posterior scalloping
Background
All types of MPS disease exhibit dysostosis multiplex to a greater or lesser degree. The role of the radiologist and other clinicians is to recognize any of these diverse changes on radiographs so that the patient can be tested to ascertain which MPS
disease is present for treatment, genetic counseling, and management. It is suspected that perhaps certain mildly affected
individuals go through life symptomatic but undiagnosed. The diagnosis is usually suggested by a combination of “clinical”
and radiographic features. The radiological manifestations play an extremely important role.
Dysostosis multiplex changes are widespread in the skeletal system and involve many different bones. At times even the
“routine” chest film will reveal changes suggesting the diagnosis of possible MPS disease.
The following mucopolysaccharidoses manifest dysostosis multiplex:
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MPS I-H (Hurler)
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MPS I-S (Scheie)
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MPS II (Hunter)
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MPS III A,B,C (Sanfilippo)
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MPS IV A,B (Morquio)
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MPS VI (Maroteaux-Lamy)
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MPS VII (Sly)
Dysostosis multiplex is also a feature of mucolipidoses and other storage diseases, including:
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Mucolipidoses [ML]:
ML II (I-Cell disease/Leroy)
ML III (Pseudo-Hurler Polydystrophy)
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Other storage diseases:
Multiple Sulfatase Deficiency
Carbohydrate-Deficient Glycoprotein Syndrome
GM I Gangliosidosis
Geleophysic Dysplasia
The following patient images show how dysostosis multiplex can affect the outward appearance of the patient.
Figure 7: Lateral spine radiograph: both superior notched and middle beaked vertebral bodies, posterior scalloping
Pelvis
Rounded iliac wings
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Ilia, tapered inferiorly
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Figure 8: Pelvis/hips radiograph: rounded iliac wings with inferior tapering
Figure 9: Pelvis/hips radiograph: inferior tapering at the expense of the acetabulae, dysplastic femoral epiphyses
Figure 10: Pelvis/hips radiograph: rounded iliac wings, tapered iliac bases with double contoured lateral walls, long femoral necks
Long Bones
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Mildly hypoplastic epiphyses [often generalized]
Long/narrow femoral neck
Hypoplastic/fragmented CFE
Thick [short] diaphyses
Proximal humeral notching
Figure 1: Full-body view of a male MPS VI patient
Figure 2: Arm and hand of a female MPS VI patient
Radiological Findings - Dysostosis Multiplex
Familiarity with the radiological findings of dysostosis multiplex will allow radiologists and other clinicians to identify patients
who may have mucopolysaccharidoses and other storage diseases so that these patients can be tested and referred for
treatment and counseling.
Figures 3 through 13 illustrate the radiographic appearance of dysostosis multiplex in multiple areas of the skeletal system in patients affected
with mucopolysaccharidoses.
Skull
Figure 11: Upper extremity radiograph: hypoplastic distal ulna and radius
Hands
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Metacarpals: Proximal pointing
Metacarpals: Thick, short, with thin cortices
Carpal bones: Irregular, hypoplastic
Tarsal bones: Irregular contours
Abnormal J-shaped sella
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Thickened diploic space
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Figure 12: Hands radiograph: severe proximal pointing of metacarpals, short/wide metacarpals with thin cortices, irregular/hypoplastic carpal bones
Figure 13: Hands radiograph: milder proximal pointing with metacarpal widening and thin cortices
Figure 3: Skull radiograph: severe abnormal J-shaped sella
Figure 4: Skull radiograph: abnormal J-shaped sella, thick diploic spaces
Thorax
Short, thick clavicles
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Paddle [oar-shaped] ribs
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Figure 5: Thorax radiograph: short thick clavicles, paddle-shaped ribs
Figure 6: Thorax radiograph: short clavicles, paddle-shaped ribs, medial humeral notching
Enzyme Replacement Therapy (ERT) for MPS VI
A new era in the treatment of the mucopolysaccharidoses (MPS) has occurred with the advent of enzyme replacement
therapy (ERT). A case in point is the new treatment Naglazyme® (galsulfase), introduced in 2005 by BioMarin Pharmaceutical
Inc., specifically for the treatment of MPS VI. It is apparent that the earlier this therapy is initiated the better the expected
results. Therefore it becomes imperative that the clinician (geneticist, pediatrician, radiologist, etc.) determine the diagnosis
as early as possible.