Crouzon Syndrome: Background, Pathophysiology, Etiology

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Overview

Background

Crouzon syndrome represents the most common syndromic craniosynostosis and 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, 5]}Virchow introduced the term craniostenosis.^[6]The type of obliterated sutures determines the type of craniostenosis. Oxycephaly, scaphocephaly, wedge skull, and oblique head are differentiated.^{[1, 3, 4, 6]}Crouzon syndrome with oxycephaly and Apert syndrome with oxycephaly and syndactylia (acrocephalosyndactyly) are the most common types of dysostosis. Some authors connect those syndromes as one, calling it Crouzon-Apert syndrome, but symptomatologic differentiation makes classification difficult. Acanthosis nigricans (shown in the image below) is the main dermatologic manifestation of Crouzon syndrome (see Acanthosis Nigricans).^{[3, 4, 7, 8]}

Acanthosis nigricans of the axillary fossa in Crouzon syndrome.

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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. Inheritance may come from an affected parent(s), although cases exist in which mutations arise de novo. Mutation of the gene (locus 10q26) for fibroblast growth factor receptor 2 (FGFR2) has been identified as a causative factor for Crouzon syndrome. Typically, the mutations occur on exons 8 or 10. 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.^{[2, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19]}

Etiology

This syndrome is inherited in an autosomal dominant pattern.^{[3, 18]}

Mutation of FGFR2^C342Y/+ is a marked cause of Crouzon syndrome that is characterized by craniosynostosis and midfacial hypoplasia. Beyond skeletal effects, the FGFR2^C342Y/+ mutation is now implicated in affecting tooth development.^{[18, 20, 21]}

Frequency

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]}

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, 6]}

Prognosis

High intracranial pressure caused by disproportion between craniostenosis and the brain growing may lead to death.^{[1, 3, 6]}

Patient Education

Found to be of high priority among craniofacial microsomia adult patients’ and caregivers’ concerns are etiological understanding, depth and availability of information, and ensuring an accurate diagnosis. Regarding etiology, frequently patients were unsure about the underlying cause. From this misunderstanding, patients were found to self-attribute incorrect origins for the disorder.^[22]

In terms of treatment, patients and caregiver expectations may need to be mitigated. Data and some adult patients having undergone surgical repairs as youths support the idea that parent caregivers may best serve their children by postponing operative intervention until children are older and are able to actively make decisions on their healthcare. Some adult patients also make the case that parents should not project their own apprehensions about the disorder on the children, which may produce negative psychological effects on the afflicted. Medical practitioners should make their best attempts to keep both patients and caregivers involved and informed of treatment plans, risks, alternative approaches where applicable, and follow-up methods of coping should surgery be elected.^{[19, 22, 23, 24]}

Furthermore, providers must exercise caution and precision in their diagnosis of associated breathing disorders. Equivocal usage of choanal atresia and choanal stenosis could add further confusion about not only etiology, but also patient and caregiver beliefs about the success of surgical procedures. Where choanal atresia is responsive to early surgery and may lessen the likelihood of later tracheostomy or continuing management, other obstructions might not be as amenable.^[25]

Clinical Presentation

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Miklaszewska M. Dysostosis cranio-facialis hederitaria. Miklaszewska M, Wasik F, eds. Dermatologia Pediatryczna. Wrocaw, Poland: Volumed; 2000. Vol 2: 650-4.
Miklaszewska M, Racawska A, Ziarkiewicz M. Syndroma Crouzon and syndromal acanthosis nigricans. Demonstration of case on the meeting of Polish Dermatological Society. February 1990.
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Media Gallery

Acrocephaly, beaked nose, "frog face," and pseudoprognathism of Crouzon syndrome.
Malposed teeth and acanthosis nigricans around the mouth in Crouzon syndrome.
No physiological spinal curvature is observed in Crouzon syndrome.
Acanthosis nigricans of the axillary fossa in Crouzon syndrome.
Short stature and dark skin of Crouzon syndrome.

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Author

Amarateedha Prak LeCourt, MD Resident Physician, Department of Anesthesiology, Naval Medical Center San Diego; Naval Flight Surgeon/Fleet Marine Force Qualified Officer, US Navy

Amarateedha Prak LeCourt, MD is a member of the following medical societies: Aerospace Medical Association, Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

Coauthor(s)

Kristina Marie Dela Rosa, MD Dermatologist, Insight Dermatology, San Diego, CA

Kristina Marie Dela Rosa, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association

Disclosure: Nothing to disclose.

Homavirak Prak University of California, Los Angeles

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Jacek C Szepietowski, MD, PhD Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland

Disclosure: Received consulting fee from Orfagen for consulting; Received consulting fee from Maruho for consulting; Received consulting fee from Astellas for consulting; Received consulting fee from Abbott for consulting; Received consulting fee from Leo Pharma for consulting; Received consulting fee from Biogenoma for consulting; Received honoraria from Janssen for speaking and teaching; Received honoraria from Medac for speaking and teaching; Received consulting fee from Dignity Sciences for consulting; .

Grazyna Szybejko-Machaj, MD, PhD Assistant Professor, Department of Dermatology, Wroclaw Medical University

Disclosure: Nothing to disclose.

Lukasz Matusiak, MD, PhD Assistant, Department and Clinic of Dermatology, Venereology and Allergology, Medical University of Wroclaw

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Mieczyslawa Miklaszewska, MD, to the development and writing of this article.

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