Genetics of Crouzon Syndrome Workup

Updated: May 06, 2015
  • Author: Harold Chen, MD, MS, FAAP, FACMG; Chief Editor: Maria Descartes, MD  more...
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Workup

Laboratory Studies

Molecular analysis in Crouzon syndrome

More than 50% of patients with Crouzon syndrome have FGFR2 mutations. FGFR2 mutations are also observed in Apert syndrome, Pfeiffer syndrome, and Jackson-Weiss syndrome.

Parental mosaicism must be checked even in apparently de novo paternal age effect syndromes such as Crouzon syndrome. With current DNA sequencing technology, detection of somatic mosaicism at levels as low as 10% should be routinely possible, and counseling of recurrence risk for paternal age-effect syndromes for a family with a single affected child should be improved. [15]

All patients with associated acanthosis nigricans have the FGFR3 Ala391Glu mutation. If testing is performed on a child with features of Crouzon syndrome during the first year of life (before the usual onset of acanthosis nigricans), concurrently testing for FGFR2 and FGFR3 mutations is recommended.

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Imaging Studies

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  • Skull radiography
    • Radiographic findings demonstrate synostosis, craniofacial deformities, digital markings of skull, basilar kyphosis, widening of hypophyseal fossa, small paranasal sinuses, and maxillary hypoplasia with shallow orbits.
    • The coronal, sagittal, lambdoidal, and metopic sutures may be involved.
  • Cervical radiography
    • Radiologic abnormalities include butterfly vertebrae and fusions of the bodies and the posterior elements.
    • Cervical fusions are present in approximately 18% of patients. C2-C3 and C5-C6 are affected equally.
    • Block fusions involving multiple vertebrae are also observed.
  • Limb radiography
    • Hand abnormalities are radiographically detectable by metacarpophalangeal analysis, although the hands are considered normal clinically.
    • Subluxation of the radial head occurs.
  • CT scanning: Comparative 3-dimensional reconstruction analysis of the calvaria and cranial bases precisely defines the pathologic anatomy and permits specific operative planning.
  • MRI: MRI is used to demonstrate occasional corpus callosum agenesis and optic atrophy.
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Other Tests

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  • Sleep study
  • Psychometric evaluation
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Histologic Findings

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  • Immunohistochemical analysis of cranial sutures, performed with labeled anti- FGFR2 antibodies, reveals that sutures from children with Crouzon syndrome demonstrate lower levels of FGFR2 activity in both stenosed and nonstenosed sutures compared with children with a nonsyndromic isolated coronal stenosis.
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