Sly Syndrome (Mucopolysaccharidosis Type VII) Clinical Presentation

Updated: Nov 30, 2017
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
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Presentation

History

As with most other mucopolysaccharidoses (MPSs), the severity of symptoms in patients with Sly syndrome (mucopolysaccharidosis type VII [MPS VII]) varies widely. Sly syndrome is a progressive, debilitating, and life-threatening disease that affects multiple organ systems.

Most severe cases of Sly syndrome present as nonimmune hydrops fetalis. Neonatal jaundice may be present at birth.

Clinical findings include macrocephaly with coarse facial features, shortened neck, variable degree of corneal opacities, auditory impairment, valvular cardiac disease, hepatosplenomegaly, inguinal and umbilical hernias, recurrent upper respiratory infections due to skeletal chest abnormalities, hirsutism, and joint contractures.

Corneal opacities may develop at any time in patients older than 1 year.

Marked growth retardation and dysostosis multiplex may develop in severe cases.

Mental retardation is a common feature of Sly syndrome but is usually moderate and nonprogressive. Other CNS concerns include hydrocephalus and neurodegenerative processes.

In milder forms of Sly syndrome, symptoms appear at age 4 years or older. 

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Physical

Clinical presentations of Sly syndrome include the following:

  • Severe and early onset form (present at birth or within the first 4 years of life): Prenatal form presents with nonimmune hydrops fetalis. Severe neonatal form presents with neonatal cholestasis with hepatosplenomegaly
  • Late onset (frequently in patients >4 years): Patients present with milder symptoms.

Major clinical manifestations include the following:

  • Dysmorphic features; macrocephaly, coarse facial features, frontal prominence, premature closure of sagittal lambdoid sutures, and a shortened neck.
  • Corneal clouding or opacity is also a feature, although it varies in age of onset. Iris colomba may be observed.
  • Auditory impairment can occur.
  • Visceral involvement and hepatosplenomegaly is a characteristic feature.
  • Gastrointestinal symptoms and ascites may develop.
  • Abnormal skeletal findings include: dysostosis multiplex, J-shaped sella turcica, platyspondyly, thoracolumbar gibbus, odontoid hypoplasia, acetabular dysplasia (dislocated hip), narrow sciatic notches, joint contractures, pointed proximal metacarpals, metatarsus adductus, short stature, dwarfism, kyphoscoliosis, and wide rib cage/shield chest (pectus carinatum).
  • Connective tissue involvement includes inguinal and umbilical hernias and, rarely, vascular anomalies.
  • Growth and development is affected by postnatal short stature, hypotonia, and neurological disorders that ultimately lead to mental retardation. Mental retardation is often moderate, nonprogressive, and most pronounced in speech and language development. [5]
  • Lymphedema/edema, heart disease (eg, valvular heart disease), and aortic regurgitation may develop.
  • Patients may be hirsute.
  • Chronic inflammatory lung disease and recurrent respiratory infections are common.
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Causes

Causes of Sly syndrome include the following:

  • Deficiency of the lysosomal enzyme beta-glucuronidase.
  • Accumulation of the undegraded mucopolysaccharides dermatan sulfate (DS), heparan sulfate (HS), and chondroitin sulfate (CS) in tissues and organs
  • Storage of excess mucopolysaccharides, contributing to numerous morphologic abnormalities

Genetic causes include the following:

  • The metabolic defect in patients with Sly syndrome has an autosomal-recessive mode of inheritance (as is true of the other MPSs, except for MPS II or Hunter syndrome, which are inherited as a sex-linked recessive trait).
  • Various mutations lead to a wide variety of phenotypes in patients with Sly syndrome.
  • The beta-glucuronidase gene has been mapped to the long arm of autosome chromosome 7 (7q), band 11.21.
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