Sections

Crouzon Syndrome

Presentation

History

History findings are described below.^{[1, 3, 6]}

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.

Visual acuity is reduced.

Physical Examination

Physical examination findings are described below.^{[1, 3, 4, 6, 25, 26, 27, 28]}

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. See an example shown below.

Deviation of the nasal septum, narrowed or obliterated anterior nares, and wide beaked nose are present.

Hypertelorism, divergent squint, eyelid scheme antimongoloid, shallow orbits, and upper eyelid falling "frog face" are observed. See the image shown below.

Acrocephaly, beaked nose, "frog face," and pseudoprognathism of Crouzon syndrome.

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Proptosis has been observed.

The upper lip is shortened and sometimes cleaved.

Malocclusion, malposed teeth, hypsistaphylia (narrow/high-arched palate), rhinolalia, and dysphasia are noted (as depicted below).

Malposed teeth and acanthosis nigricans around the mouth in Crouzon syndrome.

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Hypodontia may occur.

Characteropathy is often observed.

Short stature and no physiologic spinal curvature are observed. Children are straight as a reed. Refer to the following images.

No physiological spinal curvature is observed in Crouzon syndrome.

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Short stature and dark skin of Crouzon syndrome.

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Koilosternia rarely occurs.

Skin usually is dark.

Syndromic acanthosis nigricans appears in the axillary fossa, mouth angular, and on the lips in childhood.

In a rare case study, deep linear creases on the lips, ear lobes, palms, and soles of the feet were observed, along with redundant skin on the scalp.^[29]

In lieu of an in-person physical examination, some phenotypic assessment tools based on standardized photographs can be used to evaluate patients with general craniofacial microsomia.^[30]

Complications

Several complications can arise from Crouzon syndrome as result of its characteristic external and internal malformations.

Papilledema may occur due to intracranial hypertension.^[5]

There is a high prevalence of cerebrospinal fluid rhinorrhea.^[31]

Progressing optic nerve atrophy leads to vision impairment because of the intracranial hypertension.

One case study of a younger patient found that spontaneous prolapse of the eyeball due to rubbing occurred when shallow orbit and proptosis were present.^[32]

Impairment of hearing indicates disorders of the middle ear or, according to one case study, atresia of the external auditory canals.^[33]

Psychological and sociobehavioral issues have resulted from social stigmas associated with visible manifestations of craniosynostosis.^{[19, 22, 23, 24]}

Developmental and cognitive disabilities have been correlated with intracranial pressure from untreated craniofacial malformations (eg, cranial vault abnormalities).^{[33, 34]}

The incidence of chronic tonsillar herniation (eg, Chiari malformation type I) is correlated highly with Crouzon syndrome.^{[35, 36]}

Neurolinguistic abilities may be affected as a result of craniosynostosis.^[37]

Differential Diagnoses

Ignatowicz R, Gdakowicz B. [Craniofacial dysostosis of the Crouzon type]. Wiad Lek. 1971 Feb 15. 24(4):363-6. [QxMD MEDLINE Link].
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. 2004 May. 43(5):432-5. [QxMD MEDLINE Link].
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.
Simonin A, Maduri R, Viaroli E, Levivier M, Daniel RT, Messerer M. Correlation between Papilledema and Intracranial Hypertension in Crouzon Syndrome: A Case Report and Review of the Literature. Pediatr Neurosurg. 2019 Jul 3. 1-5. [QxMD MEDLINE Link].
Posnick JC, Ruiz RL. The craniofacial dysostosis syndromes: current surgical thinking and future directions. Cleft Palate Craniofac J. 2000 Sep. 37(5):433. [QxMD MEDLINE Link].
Gines E, Rodriguez-Pichardo A, Jorquera E, Moreno JC, Camacho F. Crouzon disease with acanthosis nigricans and melanocytic nevi. Pediatr Dermatol. 1996 Jan-Feb. 13(1):18-21. [QxMD MEDLINE Link].
Helman SN, Badhey A, Kadakia S, Myers E. Revisiting Crouzon syndrome: reviewing the background and management of a multifaceted disease. Oral Maxillofac Surg. 2014 Sep 24. [QxMD MEDLINE Link].
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. 2000 Aug. 12(8):1280-3. [QxMD MEDLINE Link].
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. 2004 Aug 24. 101(34):12555-60. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. 1996 Sep. 33(9):744-8. [QxMD MEDLINE Link].
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. 2001 Jan 1. 98(1):75-91. [QxMD MEDLINE Link].
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. 1995 Dec. 11(4):462-4. [QxMD MEDLINE Link]. [Full Text].
Fenwick AL, Goos JA, Rankin J, Lord H, Lester T, Hoogeboom AJ, et al. Apparently synonymous substitutions in FGFR2 affect splicing and result in mild Crouzon syndrome. BMC Med Genet. 2014 Aug 31. 15:95. [QxMD MEDLINE Link].
Pfaff MJ, Xue K, Li L, Horowitz MC, Steinbacher DM, Eswarakumar JVP. FGFR2c-mediated ERK-MAPK activity regulates coronal suture development. Dev Biol. 2016 Jul 15. 415 (2):242-250. [QxMD MEDLINE Link].
Hibberd CE, Bowdin S, Arudchelvan Y, Forrest CR, Brakora KA, Marcucio RS, et al. FGFR-associated craniosynostosis syndromes and gastrointestinal defects. Am J Med Genet A. 2016 Dec. 170 (12):3215-3221. [QxMD MEDLINE Link].
Azoury SC, Reddy S, Shukla V, Deng CX. Fibroblast Growth Factor Receptor 2 (FGFR2) Mutation Related Syndromic Craniosynostosis. Int J Biol Sci. 2017. 13 (12):1479-1488. [QxMD MEDLINE Link].
Al-Namnam NM, Hariri F, Thong MK, Rahman ZA. Crouzon syndrome: Genetic and intervention review. J Oral Biol Craniofac Res. 2019 Jan-Mar. 9 (1):37-39. [QxMD MEDLINE Link].
Khominsky A, Yong R, Ranjitkar S, Townsend G, Anderson PJ. Extensive phenotyping of the orofacial and dental complex in Crouzon syndrome. Arch Oral Biol. 2018 Feb. 86:123-130. [QxMD MEDLINE Link].
Barik M, Bajpai M, Malhotra A, Samantaray JC, Dwivedi S, Das S. Genome-Wide Association Study in Craniosynostosis Condition Using Innovative Systematic Bioinformatic Analysis Tools and Techniques: Future Prospective and Clinical Practice. J Pediatr Neurosci. 2018 Apr-Jun. 13 (2):170-175. [QxMD MEDLINE Link].
Luquetti DV, Brajcich MR, Stock NM, Heike CL, Johns AL. Healthcare and psychosocial experiences of individuals with craniofacial microsomia: Patient and caregivers perspectives. Int J Pediatr Otorhinolaryngol. 2018 Apr. 107:164-175. [QxMD MEDLINE Link].
Bemmels H, Biesecker B, Loewenstein J, Krokosky A, Guidotti R, Sutton EJ. Psychological and Social Factors in Undergoing Reconstructive Surgery Among Individuals with Craniofacial Conditions: An Exploratory Study. Cleft Palate Craniofac J. 2012 Feb 8. [QxMD MEDLINE Link].
Pandey N, Pandey RK, Singh RK, Shah NK. Crouzon syndrome: a social stigma. BMJ Case Rep. 2012 Oct 10. 2012:[QxMD MEDLINE Link].
Lesciotto KM, Heuzé Y, Jabs EW, Bernstein JM, Richtsmeier JT. Choanal Atresia and Craniosynostosis: Development and Disease. Plast Reconstr Surg. 2018 Jan. 141 (1):156-168. [QxMD MEDLINE Link].
Cohen MM Jr. Let's call it "Crouzonodermoskeletal syndrome" so we won't be prisoners of our own conventional terminology. Am J Med Genet. 1999 May 7. 84(1):74. [QxMD MEDLINE Link].
Ernyei S. Craniofacial dysplasia associated with congenital cataract, impairment of hearing and brachydactyly. Am J Ophthalmol. 1966 Oct. 62(4):697-702. [QxMD MEDLINE Link].
Kowalski M, Paszkowska M, Bryjanowska L. [A case of Crouzon's syndrome with coexistance of other congenital anomalies (author's transl)]. Klin Oczna. 1977 Oct. 47(10):445-7. [QxMD MEDLINE Link].
LeBlanc S, David D, Colley A, Buckley M, Roscioli T, Barnett C. Atypical Skin Manifestations in FGFR2-Related Craniosynostosis Syndromes Broaden the Phenotypic Spectrum. Mol Syndromol. 2018 May. 9 (3):149-153. [QxMD MEDLINE Link].
Birgfeld CB, Heike CL, Saltzman BS, Leroux BG, Evans KN, Luquetti DV. Reliable classification of facial phenotypic variation in craniofacial microsomia: a comparison of physical exam and photographs. Head Face Med. 2016 Mar 31. 12:14. [QxMD MEDLINE Link].
Panuganti BA, Leach M, Antisdel J. Bilateral meningoencephaloceles with cerebrospinal fluid rhinorrhea after facial advancement in the Crouzon syndrome. Allergy Rhinol (Providence). 2015 Jan. 6 (2):138-42. [QxMD MEDLINE Link].
Prasad M, Shetty AS, Shantaram M. The crouzan syndrome-a case report. J Clin Diagn Res. 2013 May. 7 (5):959-61. [QxMD MEDLINE Link].
Pal US, Gupta C, Chellappa AA. Crouzon syndrome with primary optic nerve atrophy and normal brain functions: A case report. J Oral Biol Craniofac Res. 2012 May-Aug. 2 (2):116-8. [QxMD MEDLINE Link].
Müller-Hagedorn S, Wiechers C, Arand J, Buchenau W, Bacher M, Krimmel M, et al. Less invasive treatment of sleep-disordered breathing in children with syndromic craniosynostosis. Orphanet J Rare Dis. 2018 Apr 23. 13 (1):63. [QxMD MEDLINE Link].
Cinalli G, Renier D, Sebag G, Sainte-Rose C, Arnaud E, Pierre-Kahn A. Chronic tonsillar herniation in Crouzon's and Apert's syndromes: the role of premature synostosis of the lambdoid suture. J Neurosurg. 1995 Oct. 83 (4):575-82. [QxMD MEDLINE Link].
Canpolat A, Akçakaya MO, Altunrende E, Ozlü HM, Duman H, Ton T, et al. Chiari Type I malformation yielded to the diagnosis of Crouzon syndrome. J Neurosci Rural Pract. 2014 Jan. 5 (1):81-3. [QxMD MEDLINE Link].
Maximino LP, Ducati LG, Abramides DVM, Corrêa CC, Garcia PF, Fernandes AY. Syndromic craniosynostosis: neuropsycholinguistic abilities and imaging analysis of the central nervous system. Arq Neuropsiquiatr. 2017 Dec. 75 (12):862-868. [QxMD MEDLINE Link].
Nørgaard P, Hagen CP, Hove H, Dunø M, Nissen KR, Kreiborg S, et al. Crouzon syndrome associated with acanthosis nigricans: prenatal 2D and 3D ultrasound findings and postnatal 3D CT findings. Acta Radiol Short Rep. 2012. 1 (4):[QxMD MEDLINE Link].
Keupp K, Li Y, Vargel I, et al. Mutations in the interleukin receptor IL11RA cause autosomal recessive Crouzon-like craniosynostosis. Mol Genet Genomic Med. 2013 Nov. 1 (4):223-37. [QxMD MEDLINE Link].
Lu X, Jorge Forte A, Sawh-Martinez R, Wu R, Cabrejo R, Steinbacher DM, et al. Association of Regional Cranial Base Deformity and Ultimate Structure in Crouzon Syndrome. Plast Reconstr Surg. 2019 Jun. 143 (6):1233e-1243e. [QxMD MEDLINE Link].
Seda M, Geerlings M, Lim P, Jeyabalan-Srikaran J, Cichon AC, Scambler PJ, et al. An FDA-Approved Drug Screen for Compounds Influencing Craniofacial Skeletal Development and Craniosynostosis. Mol Syndromol. 2019 Feb. 10 (1-2):98-114. [QxMD MEDLINE Link].
Maspero C, Giannini L, Galbiati G, Kairyte L, Farronato G. Non surgical treatment of Crouzon Syndrome. Stomatologija. 2014. 16(2):72-80. [QxMD MEDLINE Link].
Rathee M, Tamrakar AK, Kundu R, Yunus N. Three-dimensional precise orientation of bilateral auricular trial prosthesis using a facebow for a young adult with Crouzon syndrome. BMJ Case Rep. 2014 Aug 5. 2014:[QxMD MEDLINE Link].
Meling TR, Høgevold HE, Due-Tønnessen BJ, Skjelbred P. Comparison of perioperative morbidity after LeFort III and monobloc distraction osteogenesis. Br J Oral Maxillofac Surg. 2010 Mar 10. [QxMD MEDLINE Link].
Opitz C, Ring P, Stoll C. Orthodontic and surgical treatment of patients with congenital unilateral and bilateral mandibulofacial dysostosis. J Orofac Orthop. 2004 Mar. 65(2):150-63. [QxMD MEDLINE Link].
Scolozzi P, Herzog G, Jaques B. Simultaneous maxillo-mandibular distraction osteogenesis in hemifacial microsomia: a new technique using two distractors. Plast Reconstr Surg. 2006 Apr 15. 117(5):1530-41; discussion 1542. [QxMD MEDLINE Link].
Tessier P. The definitive plastic surgical treatment of the severe facial deformities of craniofacial dysostosis. Crouzon's and Apert's diseases. Plast Reconstr Surg. 1971 Nov. 48(5):419-42. [QxMD MEDLINE Link].
Kobayashi S, Nishiouri T, Maegawa J, Hirakawa T, Fukawa T. A novel craniofacial osteogenesis distraction system enabling control of distraction distance and vector for the treatment of syndromic craniosynostosis. J Craniofac Surg. 2012 Mar. 23(2):422-5. [QxMD MEDLINE Link].
Ko EW, Chen PK, Tai IC, Huang CS. Fronto-facial monobloc distraction in syndromic craniosynostosis. Three-dimensional evaluation of treatment outcome and facial growth. Int J Oral Maxillofac Surg. 2012 Jan. 41(1):20-7. [QxMD MEDLINE Link].
Nakajima H, Sakamoto Y, Tamada I, Ohara H, Kishi K. An internal distraction device for Le Fort distraction osteogenesis: the NAVID system. J Plast Reconstr Aesthet Surg. 2012 Jan. 65(1):61-7. [QxMD MEDLINE Link].
Kuroda S, Watanabe K, Ishimoto K, Nakanishi H, Moriyama K, Tanaka E. Long-term stability of LeFort III distraction osteogenesis with a rigid external distraction device in a patient with Crouzon syndrome. Am J Orthod Dentofacial Orthop. 2011 Oct. 140(4):550-61. [QxMD MEDLINE Link].
Tahiri Y, Taylor J. An Update on Midface Advancement Using Le Fort II and III Distraction Osteogenesis. Semin Plast Surg. 2014 Nov. 28 (4):184-92. [QxMD MEDLINE Link].
Balaji SM. Lateral canthal repositioning in syndromic, antimongoloid slant. Ann Maxillofac Surg. 2016 Jan-Jun. 6 (1):50-3. [QxMD MEDLINE Link].
Kumar A, Goel N, Sinha C, Singh A. Anesthetic Implications in a Child with Crouzon Syndrome. Anesth Essays Res. 2017 Jan-Mar. 11 (1):246-247. [QxMD MEDLINE Link].
Tripathy DK, Dhar M, Haran GH, Chauhan U. Airway management in a patient of Crouzon syndrome for maxillo-facial reconstructive surgery: Role of point-of-care ultrasonography. Indian J Anaesth. 2019 May. 63 (5):409-410. [QxMD MEDLINE Link].
Moraleda-Cibrián M, Edwards SP, Kasten SJ, Berger M, Buchman SR, O'Brien LM. Symptoms of sleep disordered breathing in children with craniofacial malformations. J Clin Sleep Med. 2014 Mar 15. 10 (3):307-12. [QxMD MEDLINE Link].

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, BA Emergency Medical Technician, Basic AirCare Ambulance; Medical Scribe, Progeny Psychiatric Group

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, The Scientific Research Honor Society

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.

Crouzon Syndrome Clinical Presentation

History

Physical Examination

Complications

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