32 Crouzon Syndrome
Craniofacial dysostosis, CFD1
Craniosynostosis, midface hypoplasia, shallow orbits, ocular proptosis, relative prognathism
Frequency: 15–16 per million births; 4.8% of babies born with craniosynostosis.
Genetics
Autosomal dominant (OMIM 123500); due to muta- tion of FGFR2 (fibroblast growth factor receptor-2) gene mapped to 10q26; allelic to Apert syndrome, Pfeiffer syndrome (one form), Jackson-Weiss syn- drome and Beare-Stevenson syndrome; Crouzon syndrome with acanthosis nigricans is due to muta- tion of FGFR3 mapped to 4p (allelic to achondropla- sia, hypochondroplasia, thanatophoric dysplasia).
Clinical Features
• Craniosynostosis, premature closure of coronal sutures
• Shallow orbits, proptosis, hypertelorism, external strabismus
• Exposure conjunctivitis or keratitis, exotropia, impaired vision
• Midface hypoplasia, beaked nose
• Hypoplastic maxilla, mandibular prognathism
• Short upper lip, drooping lower lip, lateral palatal swellings
• CNS symptoms (progressive hydrocephalus, cere- bellar tonsillar herniation, endocranial venous obstruction), hearing deficits
Differential Diagnosis
• Apert syndrome
• Saethre-Chotzen syndrome
• Carpenter syndrome
• Crouzonodermoskeletal syndrome
Radiographic Features Skull
• Progressive craniosynostosis, usually beginning during the 1st year of life and being complete by 2–3 years, ultimately involving multiple sutures (coronal + sagittal, 20%; coronal + sagittal + lambdoid, 75%; sagittal + lambdoid, 4%), brachy- cephaly in most cases
• Cloverleaf skull deformity in severely affected pa- tients
• Increased digital markings
• Maxillo-malar hypoplasia
• Upward tilting of orbital roofs, shallow orbits
• Orbital hypertelorism
• Medial and upward tilt of petrous bones
• Short and distorted zygomatic arches
• Underdeveloped frontal sinuses and mastoids
• Short and high palate, crowding of maxillary teeth, ectopic eruption of teeth
Neck
• Narrow nasopharynx, oropharynx, and trachea
• Calcification of the stylohyoid ligament Spine
• Abnormal craniocervical junction, basal impres- sion
• Cervical vertebrae fusion (C2-C3 most common)
• Butterfly vertebrae Extremities
• Cubitus valgus
• Radial head subluxation
• Carpal fusion
Crouzon Syndrome 672
Bibliography
Cohen JM. Craniosynostosis update 1987. Am J Med Genet 1988; Suppl 4: 99–148
Dodge HW, Wood MW, Kennedy RLJ. Craniofacial dysostosis:
Crouzon’s disease. Pediatrics 1959; 23: 98–106
Jabs EW. Toward understanding the pathogenesis of cran- iosynostosis through clinical and molecular correlates. Clin Genet 1998; 53: 79–86
Jabs EW, Li X, Scott AF, Meyers G, Chen W, Eccles M, Mao J, Charnas LR, Jackson CE, Jaye M. Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2. Nat Genet 1994; 8: 275–9 Kreiborh S, Jensen BL. Variable expression of Crouzon’s syn-
drome within a family. Scand J Dent Res 1977; 85: 175–84 Meyers GA, Orlow SJ, Munro JR, Przylepa KA, Jabs EW. Fibro-
blast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans.
Nat Genet 1995; 11: 462–4
Murdoch-Kinch CA, Ward RE. Metacarpophalangeal analysis in Crouzon syndrome: additional evidence for phenotypic convergence with the acrocephalosyndactyly syndromes.
Am J Med Genet 1997; 73: 61–6
Murdoch-Kinch CA, Bixler D, Ward RE. Cephalometric analy- sis of families with dominantly inherited Crouzon syn- drome: an aid to diagnosis in family studies. Am J Med Genet 1998; 77: 405–11
Tartaglia M, Bordoni V,Velardi F, Basile RT, Saulle E, Tenconi R, Di Rocco C, Battaglia PA. Fibroblast growth factor receptor mutational screening in newborns affected by metopic syn- ostosis. Childs Nerv Syst 1999; 15: 389-93
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C
Fig. 32.1. aPatient 1, age 3 years.
Triangular face, downward slanted palpebral fissures, hypertelorism, shallow orbits, and hypoplastic maxilla. (From archive of Dr. P.
Balestrazzi, University of Parma, Italy, with permission.) b Patient 2, age 6 months. Note shallow or- bits, ocular proptosis, divergent strabismus, midface hypoplasia, and low-set ears. This child had undergone reconstructive surgery when he was 3 months of age for what was initially thought to be a case of isolated trigonocephaly. In the next few months the child de- veloped a craniofacial phenotype consistent with Crouzon syn- drome. Genetic analysis disclosed a missense mutation in FGFR2.
(From Tartaglia et al. 1999)
a b
