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Crouzon Syndrome: Differential Diagnoses & Workup

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
Contributor Information and Disclosures

Updated: Sep 10, 2009

Differential Diagnoses

Apert Syndrome

Other Problems to Be Considered

  • Beare-Stevenson syndrome (OMIM 123790) - Associated with cutaneous disorders (ie, cutis gyrata and acanthosis nigricans) and FGFR2 mutations
  • Carpenter syndrome (OMIM 201000) - Autosomal recessive linked, peculiar face, absence of osseous fusion of hand bones, presence of preaxial polydactyly of hands and/or feet
  • Crouzon syndrome with acanthosis nigricans (Crouzonodermoskeletal syndrome) - Craniofacial features similar to those observed in patients with classic Crouzon syndrome (craniosynostosis with Crouzonoid facies), in addition to acanthosis nigricans and other severe physical manifestations, such as Chiari malformation, hydrocephalus, and atresia or stenosis of the choanas10 ; caused by G → A transition at nucleotide 1172 of FGFR3, resulting in an Ala391Glu (GCG → GAG) mutation in the transmembrane domain
  • FGFR3- associated coronal synostosis syndrome - Variable clinical presentation overlapping with Pfeiffer, Jackson-Weiss, or Saethre-Chotzen syndrome phenotypes (Some individuals with a disease-causing mutation may have no clinical problems.)
  • Jackson-Weiss syndrome (OMIM 123150) - Broad great toes with varus deviation and tarsal/metatarsal fusions, lack of thumb abnormalities, craniofacial features suggestive of Pfeiffer syndrome, FGFR2 mutations
  • Pfeiffer syndrome (OMIM 101600) - Both hand and foot abnormalities characterized by broad thumbs and halluces with occasional cutaneous syndactyly, mild cranial deformities, lack of osseous fusion of the phalanges, FGFR1 and FGFR2 mutations
  • Saethre-Chotzen syndrome (OMIM 101400) - Characteristic facies, relatively mild cranial deformity, normal thumbs, lack of osseous fusion of the hand bones (Approximately 75% of patients have identifiable mutations in the TWIST gene.)

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.
    • 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.

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.

Other Tests

  • Sleep study
  • Psychometric evaluation

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.

More on Crouzon Syndrome

Overview: Crouzon Syndrome
Differential Diagnoses & Workup: Crouzon Syndrome
Treatment & Medication: Crouzon Syndrome
Follow-up: Crouzon Syndrome
Multimedia: Crouzon Syndrome
References
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References

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Further Reading

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Keywords

acrocephalosyndactyly type II, craniofacial dysostosis, craniostenosis Crouzon type, Crouzon craniofacial dysostosis, calvarial deformities, facial anomalies, exophthalmos, craniosynostosis, Crouzon syndrome, Crouzon's syndrome, hypertelorism, exophthalmos, strabismus, beaked nose, short upper lip, hypoplastic maxilla, mandibular prognathism, fibroblast growth factor receptor-2, FGFR2 gene, FGFR3 gene, FGFR1 gene, upper airway obstruction, respiratory distress, septal deviation, conductive deafness, Ménière disease

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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 Medical Association, American Society of Human Genetics, and Teratology Society
Disclosure: Nothing to disclose.

Medical Editor

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: Radiation Research Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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.

CME Editor

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, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, 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.

 
 
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