Diagnostic Considerations

Other rare skeletal diseases such as spondyloepiphyseal dysplasias (SED) and spondylometaphyseal dysplasia (SMD) have skeletal manifestations that are similar to those of Morquio A syndrome (mucopolysaccharidosis type IVA [MPS IVA]). Congenital SED can usually be distinguished from Morquio A syndrome because the skeletal deformity in patients with congenital SED is present at birth. However, it is very difficult to differentiate Morquio A syndrome from other types of SED during the neonatal period. Radiographs from patients with two other types of SED, Dyggve-Melchior-Clausen syndrome (DMC) and Smith-McCort syndrome (SMC), show a characteristic lacelike appearance of the iliac crests,^[43]which is absent in patients with Morquio A syndrome. DMC can be clinically distinguished from Morquio A syndrome, since DMC causes intellectual disability. Morquio syndrome is also unique from other MPSs because the brain is not affected and it may not result in corneal clouding.

Differential Diagnoses

Hunter Syndrome (Mucopolysaccharidosis Type II)
Sanfilippo Syndrome (Mucopolysaccharidosis Type III)
Maroteaux-Lamy Syndrome (Mucopolysaccharidosis Type VI)
Sly Syndrome (Mucopolysaccharidosis Type VII)
GM1 Gangliosidosis
Mucolipidosis II
Mucolipidosis III
Mucopolysaccharidosis Type I H/S
Mucopolysaccharidosis Type IH
Mucopolysaccharidosis Type IS
Spondyloepiphyseal dysplasias (SED)
Spondylometaphyseal dysplasia (SMD)

Workup

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Elosulfase alfa (Vimizim®) voor Morquio A syndroom voldoet niet aan de stand van de wetenschap en praktijk.
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Media Gallery

Lateral view of spine in a child aged 8 years and 7 months. This radiograph shows advanced platyspondyly, irregularity, and anterior beaking of vertebral bodies characteristic of dysostosis multiplex. Note also the gibbus deformity and lordosis, which are characteristic of Morquio syndrome.
Cervical spine, flexion and extension views, in a child aged 5 years and 11 months. These flexion and extension images depict anterior and posterior subluxation, respectively, of the atlas secondary to odontoid hypoplasia.
Bilateral lower extremity views in a patient aged 22 years and 6 months. Metaphyseal irregularities and the characteristic genu valgus deformity are easily observed in this image.
Bilateral hand radiographs in a patient aged 22 years and 6 months. Note the tapering of the proximal portion of metacarpals 2 through 5 and small irregular carpal bones. The epiphyseal involvement characteristic of Morquio syndrome is exemplified by the tapered irregular distal radius and ulna. Overall, the bones are osteopenic with cortical thinning.
Upper extremities in a child aged 6 years and 11 months. Note the irregular epiphyses and widened metaphyses. Cortical thinning and mild widening of the diaphysis of the humerus are visible.
Multiple abnormalities are present in the pelvis, including dysplastic femoral heads and oblique acetabular roof with coxa valgus deformity. Flared iliac wings usually observed in Morquio syndrome are not well represented in this radiograph.
Anteroposterior view of the chest in a child aged 8 years and 4 months with Morquio syndrome. To reference the relatively small size of this chest, this patient's vital capacity was 500 cc, but the expected value based on height and weight was 1400 cc. Widened metaphyses and irregular epiphyses of the humeri and generalized platyspondyly are present. Oar-shaped ribs (widening ribs anteriorly and narrowing at the vertebrae) are easily observed and are another key characteristic of dysostosis multiplex.
Defects in keratan sulfate (KS) degradation resulting in Morquio syndrome.
The individual on the front of the scooter is 19 years old and has Morquio syndrome. Her friend on the back is an average-stature 10 year old without Morquio syndrome. On the driver, note the enlargement at the knees and the wrist deformity. Also, note the successful adaptation of the scooter to ambulate.
Note the short trunk and protuberant rib structure in this child with Morquio syndrome. More importantly, notice that Morquio syndrome is not preventing this child from being active and fishing.
Clinical pictures of patients with Morquio A syndrome (mucopolysaccharidosis type IVA [MPS IVA]). Left panel: a 31-year-old female patient with a severe form. Middle panel: an 18-year-old male patient with an intermediate form. Right panel: a 25-year-old male patient with a mild form. Courtesy of the Carol Ann Foundation; image adapted from Educational CD for International Morquio Organization.
Clinical features of a patient with Morquio A syndrome (mucopolysaccharidosis type IVA [MPS IVA]). This patient had a severe form of MPS IVA at age 3 years and had bone abnormalities of pectus carinatum, kyphoscoliosis, genu valgum, short stature, prominent forehead, and abnormal gait (height, 90 cm; 50th percentile of male MPS IVA growth chart; body weight, 14 kg). Courtesy of the Carol Ann Foundation; image adapted from Educational CD for International Morquio Organization.
MRI of the cervical spine in a patient aged 4 years. A baseline study of the upper cervical anatomy is recommended no later than age 2 years or at diagnosis using flexion/extension radiography. If severe pain or pain associated with weakness or strength or tremors (or clonus) in the arms or legs occurs, the patient should undergo studies of the neck to evaluate for the slippage (subluxation) of the neck vertebrae and compression of the spinal cord. Radiography and MRI are performed with the head bent forward (flexion) and with the neck back (extension) and is performed annually for monitoring. Courtesy of the Carol Ann Foundation; image adapted from Educational CD for International Morquio Organization.
Clinical picture of hip deformity in an 8-year-old patient with Morquio A syndrome (mucopolysaccharidosis type IVA [MPS IVA]). Multiple abnormalities are shown in the hip, including spondyloepiphyseal dysplastic femoral heads, oblique acetabular roof with coxa valgus deformity, and flared iliac wings. Courtesy of the Carol Ann Foundation; image adapted from Educational CD for International Morquio Organization.
Skeletal/joint disease - hands. Bilateral hand radiographs in a patient aged 6 years. Note the tapering of the proximal portion of metacarpals 2 through 5 and small irregular carpal bones. The joints may become hyperlaxity by age 2 years. Eventually, the hands take on a characteristic tilting of the radial epiphysis toward the ulna due to a combination of metaphyseal deformities, hypoplasia of the bones, and degradation of connective tissues near the joint secondary to GAG accumulation. Courtesy of the Carol Ann Foundation; image adapted from Educational CD for International Morquio Organization.
Skeletal/joint disease - hands. The epiphyseal involvement characteristic of Morquio syndrome is exemplified by the tapered irregular distal radius and ulna. Overall, the bones are osteopenic with cortical thinning. Upper extremities in a child aged 2 years, 3 months (left panel). Note the irregular epiphyses and widened metaphyses. Cortical thinning and mild widening of the diaphysis of the humerus are visible. With aging, the bone deformity progresses, eg, with the tilting of the radial epiphysis toward the ulna. The humerus usually appears shortened later. Courtesy of the Carol Ann Foundation; image adapted from Educational CD for International Morquio Organization.
Skeletal/joint disease - hands. Unlike other mucopolysaccharidoses, Morquio syndrome is associated with ligamentous laxity. The cause of abnormal joint function remains unknown, presumably derived from a combination of metaphyseal deformities, hypoplasia of the bones, and degradation of connective tissues near the joint secondary to GAG accumulation. The wrist and fingers (small joints) are usually extremely weak, resulting in a very weak grip. Difficulties with dressing, personal hygiene, and writing can result from this hypermobile ligament. Range-of-motion exercises, swimming, and computer typing appear to offer some benefits in preserving joint function and fine motor skills and should be started early in the clinical course. Wrist splints and plastic braces may benefit fine motor functioning. The indication of physical therapy and its benefits in Morquio syndrome should be studied further. Courtesy of the Carol Ann Foundation; image adapted from Educational CD for International Morquio Organization.
Skeletal/joint problem – hands and legs. This 10-year-old patient with Morquio A syndrome (mucopolysaccharidosis type IVA [MPS IVA]) showed skeletal habitus with a disproportionate short stature of short trunk type with relatively long extremities. The upper extremities show lateral bowing and prominence of the radius. In the lower extremities, there is genu valgum (knocked knee). A skew foot posture is seen in both feet, as well as increased sandal gap between toes 1 and 2. Extreme ligamentous laxity permits very hypermobile knees, fingers, and wrists. The feet show pronated pes planus. Muscle bulk is reduced, particularly in the extremities. Generalized mild to moderate hypotonia is present. Courtesy of the Carol Ann Foundation; image adapted from Educational CD for International Morquio Organization.
Spinal cord pathophysiology. Odontoid hypoplasia is the most critical skeletal feature to be recognized in any patient with Morquio syndrome (mucopolysaccharidosis type IV [MPS IV]). This, in combination with ligamentous laxity and extradural mucopolysaccharide deposition, results in atlantoaxial subluxation, with consequential quadriparesis or even death. Another potential complication is cervical myelopathy. A history of exercise intolerance in patients with MPS IV often predicts occult cervical myelopathy, which can also cause bowel and bladder dysfunction and compression of the spinal cord, leading to weakness or paralysis. Mortality and morbidity are primarily related to the atlantoaxial instability and subsequent cervical myelopathy, and patients with a severe form, primarily related to cervical instability, often do not survive beyond the second or third decade of life. A minor fall or extension of the neck can result in spinal cord injury and subsequent quadriparesis or sudden death. Courtesy of the Carol Ann Foundation; image adapted from Educational CD for International Morquio Organization.
Pathophysiology of difficult airway in Morquio A syndrome. Both restrictive and obstructive respiratory pathology are common in patients with Morquio A syndrome. The restrictive defect results from thoracic cage deformity, and the obstructive defect is caused by tracheobronchial abnormalities, large tongue and mandible, adenoidal, tonsillar, and vocal cord hypertrophy by the accumulation of storage materials. An imbalance of growth between trachea, cervical spine, and brachiocephalic artery causes tracheal obstruction. Moreover, individuals with Morquio A syndrome have small nasal passages caused by thickened mucous membranes and thick and copious secretions. Chronic upper respiratory tract infection further decreases the already diminished airway lumen. Courtesy of the Carol Ann Foundation; image adapted from Educational CD for International Morquio Organization.
Tracheal obstruction. CT angiography in a 29-year-old patient shows severe tracheal obstruction. Tracheal narrowing (T; trachea), often due to compression from the crossing brachiocephalic (innominate) artery, increases with age. Note the position of the brachiocephalic artery (A) anterior to the trachea. Cervicothoracic spine moves forward while a severe pectus carinatum (M: manubrium) compresses backward. Courtesy of the Carol Ann Foundation; image adapted from Educational CD for International Morquio Organization.

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Author

Kazuki Sawamoto, PhD, MS Postdoctoral Research Fellow, Skeletal Dysplasia Lab, Pediatric Orthopedic Surgery, Nemours Alfred I duPont Hospital for Children

Disclosure: Nothing to disclose.

Coauthor(s)

Melodie Melbouci University of Delaware

Disclosure: Nothing to disclose.

Adriana M Montaño, PhD Professor, Department of Pediatrics, Department of Biochemistry and Molecular Biology, Vice Dean for Research, Doisy Research Center, St Louis University School of Medicine

Adriana M Montaño, PhD is a member of the following medical societies: American Society of Gene and Cell Therapy, American Society of Human Genetics, Japanese Society for Inherited Metabolic Diseases, Little People of America, Molecular Biology Society of Japan, Society for the Study of Inborn Errors of Metabolism, The Genetics Society of Japan

Disclosure: Nothing to disclose.

William G Mackenzie, MD Professor of Orthopedic Surgery, Jefferson Medical College of Thomas Jefferson University; Chairman, Department of Orthopedics, Co-Director, Muscular Dystrophy Association Clinic, Nemours Alfred I duPont Hospital for Children

William G Mackenzie, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Medical Association, American Orthopaedic Association, Canadian Orthopaedic Association, College of Physicians and Surgeons of British Columbia, Dwarf Athletic Association of America, Eastern Orthopaedic Association, European Paediatric Orthopaedic Society, International Federation of Paediatric Orthopaedic Societies, International Pediatric Orthopaedic Think Tank, International Society of Orthopaedic Surgery and Traumatology, Limb Lengthening and Reconstruction Society, Little People of America, Pediatric Orthopaedic Society of North America, Royal College of Physicians and Surgeons of Canada

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: BioMarin<br/>Received research grant from: BioMarin<br/>Received income in an amount equal to or greater than $250 from: BioMarin paid to Honorarium<br/>Board Memberships for: MPS; Little People of America.

Mary C Theroux, MD Professor of Anesthesiology and Pediatrics, Sidney Kimmel Medical College of Thomas Jefferson University; Director of Anesthesiology Research, Staff Pediatric Anesthesiologist, Department of Anesthesiology and Critical Care Medicine, Nemours Alfred I duPont Hospital for Children

Mary C Theroux, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Anesthesiologists, Association of University Anesthetists, International Anesthesia Research Society, Society for Pediatric Anesthesia

Disclosure: Nothing to disclose.

Christian Pizarro, MD Professor of Surgery and Pediatrics, Sidney Kimmel Medical College of Thomas Jefferson University; Chief of Cardiothoracic Surgery, Director, Nemours Cardiac Center, Nemours Alfred I duPont Hospital for Children

Christian Pizarro, MD is a member of the following medical societies: American Association for Thoracic Surgery, American College of Surgeons, American Heart Association, American Medical Association, Congenital Heart Surgeons Society, European Association for Cardio-Thoracic Surgery, International Society for Heart and Lung Transplantation, Society for Cardiothoracic Surgery in Great Britain and Ireland, Society of Thoracic Surgeons, World Society for Pediatric and Congenital Heart Surgery

Disclosure: Nothing to disclose.

Julie Hoover-Fong, MD, PhD, FACMG Professor, Department of Genetic Medicine, Director, Greenberg Center for Skeletal Dysplasias, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

Julie Hoover-Fong, MD, PhD, FACMG is a member of the following medical societies: American College of Medical Genetics and Genomics, American Society of Human Genetics, International Skeletal Dysplasia Society

Disclosure: Nothing to disclose.

Michael C Ain, MD Associate Professor, Departments of Neurosurgery and General Surgery, Division of Pediatric Orthopaedic Surgery, Johns Hopkins University School of Medicine

Michael C Ain, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Association, Scoliosis Research Society, Pediatric Orthopaedic Society of North America

Disclosure: Nothing to disclose.

Shunji Tomatsu, MD, PhD Professor, Department of Pediatrics, Jefferson Medical College of Thomas Jefferson University; Principal Research Scientist and Director, Skeletal Dysplasia Lab, Departments of Biomedical Research and Orthopedics, Nemours/Alfred I duPont Hospital for Children; Professor, Department of Pediatrics, St Louis University School of Medicine; Adjunct Professor, Department of Pediatrics, Shimane Medical University and Gifu University School of Medicine, Japan

Shunji Tomatsu, MD, PhD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Received research grant from: R01HD065767; P30GM114736; the Austrian MPS Society; The Bennett Foundation; Carol Ann Foundation. .

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Margaret M McGovern, MD, PhD Professor and Chair of Pediatrics, Stony Brook University School of Medicine

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Karl S Roth, MD Retired Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, The Scientific Research Honor Society, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Nancy E Braverman, MD, MS Associate Professor, Department of Human Genetics, McGill University Faculty of Medicine, Canada

Nancy E Braverman, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American Society of Human Genetics, Society for Inherited Metabolic Disorders, Society for the Study of Inborn Errors of Metabolism

Disclosure: Nothing to disclose.

Acknowledgements

Authors' note: Kazuki Sawamoto, PhD, MS, Melodie Melbouci, and Adriana M Montaño Suárez, PhD, have contributed equally to the current updated version of this article.

Sections Morquio Syndrome (Mucopolysaccharidosis Type IV)
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Morquio Syndrome (Mucopolysaccharidosis Type IV) Differential Diagnoses

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