Crouzon Syndrome Author: Lukasz Matusiak, MD; Chief Editor: Dirk M Elston, MD more...BackgroundCrouzon 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 (Cierre de la sutura coronal), scaphocephaly (Cierre de la sutura sagital), wedge skull, and oblique head are differentiated.[1, 3, 4, 5] Crouzon syndrome with oxycephaly and Apert syndrome (craneosinostosis genetica) with oxycephaly and syndactylia (acrocephalosyndactyly Apert. ) 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 (shown in the image below) is the main dermatologic manifestation of Crouzon syndrome (see Acanthosis Nigricans).[3, 4, 6] Acanthosis nigricans of the axillary fossa in Crouzon syndrome. PathophysiologyDysplasias (anormalidad en el desarrollo de un tejido.) 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.[2, 7, 8, 9, 10, 11, 12] EpidemiologyFrequencyInternationalThe 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/MorbidityHigh intracranial pressure caused by disproportion between craniostenosis and brain growing may lead to death.[1, 3, 5] RaceRace is not noted as a predisposing factor.[3] SexSex factor does not play any role.[3] AgeDeformation of bony face is visible just after the birth. Other syndrome factors reveal themselves with time.[3, 5] Clinical PresentationHistoryHistory 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.PhysicalPhysical 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. See an example shown below. Acrocephaly, beaked nose, "frog face," and pseudoprognathism of Crouzon syndrome. 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. See the image shown below. Acrocephaly, beaked nose, "frog face," and pseudoprognathism of Crouzon syndrome. 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 (as depicted below). Malposed teeth and acanthosis nigricans around the mouth in Crouzon syndrome. 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. Short stature and dark skin of Crouzon syndrome. Koilosternia rarely occurs. Skin usually is dark. Syndromic acanthosis nigricans appears in the axillary fossa, mouth angular, and on the lips in childhood.CausesThis syndrome is inherited in an autosomal dominant pattern.[3] WorkupLaboratory StudiesHistopathologic examination of skin changes can reveal acanthosis nigricans.Imaging StudiesImaging 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 TestsOther tests may include the following: 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 testingHistologic FindingsHistologic 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 & ManagementSurgical CareA 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.Facial plastic surgery can be of great benefit.[16] It is usually based on various craniofacial osteogenesis distraction methods and systems; patients usually wear a custom-fitted helmet (or cranial band) for several months after surgery.[5, 17, 18, 19, 20, 21, 22, 23] It is one of the few syndromes for which the cosmetic results of the surgery can be strikingly effective. The surgery minimizes the risk linked to the neurological complications, but also has an impact on stigmatization feelings, the psychological and social implications.[24] ConsultationsConsultations with ophthalmologists, laryngologists, neurologists, psychiatrists, and stomatologists are usually required.Follow-upFurther Inpatient CareOphthalmologists and neurologists should monitor patients with Crouzon syndrome.