Genetics of Crouzon Syndrome Workup

  • Author: Harold Chen, MD, MS, FAAP, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Aug 11, 2011
 

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.[12]

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

  • 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

  • Sleep study
  • Psychometric evaluation
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Histologic Findings

  • 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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Contributor Information and Disclosures
Author

Harold Chen, MD, MS, FAAP, FACMG  Professor, Departments of Pediatrics, Obstetrics and Gynecology, and Pathology, Director of Genetic Laboratory Services, Louisiana State University Medical Center

Harold Chen, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael Fasullo, PhD  Senior Scientist, Ordway Research Institute; Associate Professor, State University of New York at Albany; Adjunct Associate Professor, Center for Immunology and Microbial Disease, Albany Medical College

Michael Fasullo, PhD is a member of the following medical societies: American Society for Biochemistry and Molecular Biology, Environmental Mutagen Society, Genetics Society of America, and Radiation Research Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David Flannery, MD, FAAP, FACMG  Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

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Child with Crouzon syndrome. Note midfacial hypoplasia, proptosis secondary to shallow orbits, and ocular hypertelorism.
 
 
 
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