AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Acknowledgments
• Multimedia
• References

Background

Crouzon syndrome was described in 1912 as one of the varieties of craniofacial dysostosis caused by premature obliteration and ossification of two or more sutures, most often coronal and sagittal.^{1, 2, 3, 4} Virchow introduced the term craniostenosis.⁵ The type of obliterated sutures determines the type of craniostenosis. Oxycephaly, scaphocephaly, wedge skull, and oblique head are differentiated.^{1, 3, 4, 5} Crouzon syndrome with oxycephaly and Apert syndrome with oxycephaly and syndactylia (acrocephalosyndactyly) are the most common cases of dysostosis. Some authors connect those syndromes as one, calling it Crouzon-Apert syndrome, but symptomatologic differentiation makes classification difficult. Acanthosis nigricans is the main dermatologic manifestation of Crouzon syndrome (see Acanthosis Nigricans).^{3, 4, 6}

Pathophysiology

Dysplasias of the skeleton (including craniofacial dysostosis) are caused by the malformations of the mesenchyme and ectoderm. The unknown teratogenic factors are taken into account. Dysplasias are inherited in an autosomal dominant pattern. Mutation of the gene (locus 10q26) for fibroblast growth factor receptor 2 (FGFR2) could be responsible for Crouzon syndrome. Moreover, the mutation in the transmembrane region of FGFR3 (locus 4p16.3) was detected in this syndrome and was observed in cases with acanthosis nigricans coexistence.^{7, 8, 9, 2, 10, 11, 12}

The Medscape Genomic Medicine Resource Center may be helpful.

Frequency

International

The prevalence is very low; Crouzon syndrome is currently estimated to occur in 1 in 25,000 people in the general population.⁴ Crouzon syndrome is rare worldwide.^{3, 4}

Mortality/Morbidity

High intracranial pressure caused by disproportion between craniostenosis and brain growing may lead to death.^{1, 3, 5}

Race

Race is not noted as a predisposing factor.³

Sex

Sex factor does not play any role.³

Age

Deformation of bony face is visible just after the birth. Other syndrome factors reveal themselves with time.^{3, 5}

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Acknowledgments
• Multimedia
• References

History

History findings are as follows^{1, 3, 5}:

• Bony face deformity is observed at birth, followed with time by other factors of the syndrome.
• Patients report headache.
• Convulsions often occur; mental retardation is frequently observed.

Physical

Physical findings are as follows^{1, 3, 4, 5, 13, 14, 15}:

• Coronal and sagittal sutures are obliterated; fontanels remain not obliterated and pulsating for a long time.
• Lateral and anteroposterior flattening of the acrocranium is observed, growing only at the vertical axis.
• Anteroposterior diameter is smaller than transverse diameter.
• The forehead is high and wide.
• Wide face and hypoplastic maxilla producing pseudoprognathism are observed.
• Deviation of the nasal septum, narrowed or obliterated anterior nares, and wide beaked nose are present.
• Hypertelorism, divergent squint, eyelid scheme antimongoloid, and upper eyelid falling "frog face" are observed.
• The upper lip is shortened and sometimes cleaved.
• Progressing optic nerve atrophy leads to vision impairment because of the intracranial hypertension.
• Impairment of hearing indicates disorders of the middle ear.
• Malocclusion, malposed teeth, hypsistaphylia (narrow/high-arched palate), rhinolalia, and dysphasia are noted.
• Characteropathy is often observed.
• Short stature and no physiologic spinal curvature are observed. Children are straight as a reed.
• Koilosternia rarely occurs.
• Skin usually is dark.
• Syndromic acanthosis nigricans appears in the axillary fossa, mouth angular, and on the lips in childhood.

Causes

This syndrome is inherited in an autosomal dominant pattern.³

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

Consider the following other problems^{1, 3, 14}:

• Apert syndrome/acrocephalosyndactylia
• Franceschetti-Zwahlen syndrome
• Marie-Sainton syndrome
• Greig syndrome

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Acknowledgments
• Multimedia
• References

Lab Studies

• Histopathologic examination of skin changes - Acanthosis nigricans

Imaging Studies

Imaging studies are as follows^{1, 3, 4, 5}:

• Skull, spine, and hand radiography is usually necessary to confirm the diagnosis.
• Skull radiography reveals the following:
• • Oxycephaly - Acrocranium (most characteristic), obliterated sutures (mostly coronal, sagittal)
  • Deep digitate impression, shallow eye sockets (exophthalmos)
  • Turkish saddle deepened with osseous sternum connecting anterior and posterior clinoid processes
  • Shortened anterior cranial fossa
  • Underdeveloped lateral nasal sinuses
  • Tympanic membranes fixed oblique, narrowed external auditory canals, absence of mastoid processes pneumatization, and small pyramids with symptoms of sclerosis
• On spine radiography, lumbarization and the presence of bifid spinous process are possible, and slight symptoms of achondroplasia may be visible.
• Radiographic examination of the metacarpal bones and fingers reveals slight achondroplasia.

Other Tests

• Ophthalmologic examination with ophthalmoscopy
• Laryngologic examinations with audiography
• General physical examination with ECG
• Psychiatric examinations and psychological testing
• Stomatologic examination
• EEG - Low-voltage, increased convulsive excitability
• Genetic testing

Histologic Findings

Histologic features of acanthosis nigricans include hyperkeratosis, acanthosis, and papillomatosis. In the basal layer, the amount of pigment cells is also increased in the upper dermis. No difference exists in histologic features of acanthosis nigricans among symptomatic, benign, and malignant forms.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Acknowledgments
• Multimedia
• References

Surgical Care

A neurosurgical procedure is recommended in cases of intracranial hypertension leading to further optic atrophy. This surgery is difficult, and the procedure must be considered and undertaken in stages. Plastic surgery of the face could be of great help. Many patients usually wear a custom-fitted helmet (or cranial band) for several months after surgery.^{5, 16, 17, 18} It is one of the few syndromes for which the cosmetic results of the surgery can be strikingly effective.

Consultations

Consultations with ophthalmologists, laryngologists, neurologists, psychiatrists, and stomatologists are usually required.

FOLLOW-UP

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Acknowledgments
• Multimedia
• References

Further Inpatient Care

Ophthalmologists and neurologists should monitor patients with Crouzon syndrome.

ACKNOWLEDGMENTS

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Acknowledgments
• Multimedia
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Mieczyslawa Miklaszewska, MD, and Grazyna Szybejko-Machaj, MD, to the development and writing of this article.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Acknowledgments
• Multimedia
• References

Media file 1:  Acrocephaly, beaked nose, "frog face," and pseudoprognathism of Crouzon syndrome.
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Media file 2:  Malposed teeth and acanthosis nigricans around the mouth in Crouzon syndrome.
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Media file 3:  No physiological spinal curvature is observed in Crouzon syndrome.
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Media file 4:  Acanthosis nigricans of the axillary fossa in Crouzon syndrome.
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Media file 5:  Short stature and dark skin of Crouzon syndrome.
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Media type:  Photo

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Acknowledgments
• Multimedia
• References

1. Ignatowicz R, Gdakowicz B. [Craniofacial dysostosis of the Crouzon type]. Wiad Lek. Feb 15 1971;24(4):363-6. [Medline].
2. Maeda T, Hatakenaka M, Muta H, Nakayama M, Nakazaki Y, Hiroyama T, et al. Clinically mild, atypical, and aged craniofacial syndrome is diagnosed as Crouzon syndrome by identification of a point mutation in the fibroblast growth factor receptor 2 gene (FGFR2). Intern Med. May 2004;43(5):432-5. [Medline].
3. Miklaszewska M. Dysostosis cranio-facialis hederitaria. In: Miklaszewska M, Wasik F, eds. Dermatologia Pediatryczna. Vol 2. Wrocaw, Poland: Volumed; 2000:650-4.
4. Miklaszewska M, Racawska A, Ziarkiewicz M. Syndroma Crouzon and syndromal acanthosis nigricans. Demonstration of case on the meeting of Polish Dermatological Society; February 1990.
5. Posnick JC, Ruiz RL. The craniofacial dysostosis syndromes: current surgical thinking and future directions. Cleft Palate Craniofac J. Sep 2000;37(5):433. [Medline].
6. Gines E, Rodriguez-Pichardo A, Jorquera E, Moreno JC, Camacho F. Crouzon disease with acanthosis nigricans and melanocytic nevi. Pediatr Dermatol. Jan-Feb 1996;13(1):18-21. [Medline].
7. Bodo M, Baroni T, Carinci F, Becchetti E, Conte C, Bellucci C, et al. Interleukin secretion, proteoglycan and procollagen alpha(1)(I) gene expression in Crouzon fibroblasts treated with basic fibroblast growth factor. Cytokine. Aug 2000;12(8):1280-3. [Medline].
8. Eswarakumar VP, Horowitz MC, Locklin R, Morriss-Kay GM, Lonai P. A gain-of-function mutation of Fgfr2c demonstrates the roles of this receptor variant in osteogenesis. Proc Natl Acad Sci U S A. Aug 24 2004;101(34):12555-60. [Medline].
9. Kress W, Collmann H, Büsse M, Halliger-Keller B, Mueller CR. Clustering of FGFR2 gene mutations inpatients with Pfeiffer and Crouzon syndromes (FGFR2-associated craniosynostoses). Cytogenet Cell Genet. 2000;91(1-4):134-7. [Medline].
10. Wilkes D, Rutland P, Pulleyn LJ, Reardon W, Moss C, Ellis JP, et al. A recurrent mutation, ala391glu, in the transmembrane region of FGFR3 causes Crouzon syndrome and acanthosis nigricans. J Med Genet. Sep 1996;33(9):744-8. [Medline].
11. Schweitzer DN, Graham JM Jr, Lachman RS, Jabs EW, Okajima K, Przylepa KA, et al. Subtle radiographic findings of achondroplasia in patients with Crouzon syndrome with acanthosis nigricans due to an Ala391Glu substitution in FGFR3. Am J Med Genet. Jan 1 2001;98(1):75-91. [Medline].
12. Meyers GA, Orlow SJ, Munro IR, Przylepa KA, Jabs EW. Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. Nat Genet. Dec 1995;11(4):462-4. [Medline]. [Full Text].
13. Cohen MM Jr. Let's call it "Crouzonodermoskeletal syndrome" so we won't be prisoners of our own conventional terminology. Am J Med Genet. May 7 1999;84(1):74. [Medline].
14. Ernyei S. Craniofacial dysplasia associated with congenital cataract, impairment of hearing and brachydactyly. Am J Ophthalmol. Oct 1966;62(4):697-702. [Medline].
15. Kowalski M, Paszkowska M, Bryjanowska L. [A case of Crouzon's syndrome with coexistance of other congenital anomalies (author's transl)]. Klin Oczna. Oct 1977;47(10):445-7. [Medline].
16. Opitz C, Ring P, Stoll C. Orthodontic and surgical treatment of patients with congenital unilateral and bilateral mandibulofacial dysostosis. J Orofac Orthop. Mar 2004;65(2):150-63. [Medline].
17. Scolozzi P, Herzog G, Jaques B. Simultaneous maxillo-mandibular distraction osteogenesis in hemifacial microsomia: a new technique using two distractors. Plast Reconstr Surg. Apr 15 2006;117(5):1530-41; discussion 1542. [Medline].
18. Tessier P. The definitive plastic surgical treatment of the severe facial deformities of craniofacial dysostosis. Crouzon's and Apert's diseases. Plast Reconstr Surg. Nov 1971;48(5):419-42. [Medline].

Article Last Updated: Jul 2, 2008