Crouzon Syndrome: Phenotypic Signs and Symptoms of the Postnatally Expressed Subtype

Abstract

In a retrospective study, the characteristics of a group of patients (n = 9) with a postnatally expressed Crouzon syndrome were described. Although they do not always display the physical signs of craniosynostosis, such patients are highly at risk of developing symptoms secondary to multiple suture synostosis. By reviewing the hospital files, radiographs, and three-dimensional computed tomography scans of these patients, it was possible to describe the pattern of suture obliteration chronologically. Furthermore, certain phenotypic signs and symptoms such as skull shape and development of digital impressions, a bulge at the bregma, and intracranial hypertension were inventoried as well as patients' genotypes. Interestingly, ossification started at the lambdoid sutures in at least four patients and most likely in three additional ones. The coronal sutures were the last to ossify in at least three of the patients. Various skull shapes were encountered. Furthermore, all nine patients developed digital impressions, starting occipitally in eight of them. Seven patients developed a bulge at the bregma, and four of them exhibited intracranial hypertension. The genotype varied in our patients. To recognize patients with postnatal Crouzon syndrome as soon as possible, special attention must be paid to 1) occipital development of digital impressions and/or ossification of sutures, 2) development of a prominent bregma, 3) development of intracranial hypertension, and/or 4) progressive characteristic "crouzonoid" features. Such patients can be considered as representing a subtype of Crouzon syndrome. To prevent or treat intracranial hypertension and/or loss of vision, surgical intervention should be performed at the onset of progressive craniosynostosis between 1 and 2 years of age.

Foramen Magnum Size and Involvement of Its Intraoccipital Synchondroses in Crouzon Syndrome

“…22,23 In addition, animal studies have revealed that FGFR2 is expressed at the neural tube and cranial base during embryogenesis. [24][25][26][27] Several studies reported abnormalities of the skull 2,5,9,28,29 and skull base 9,13,30 in Crouzon syndrome in humans and in mice. [31][32][33] Thus, it is likely that FGFR2 gene mutations have an effect on hindbrain development and give rise to abnormal growth of its surrounding bone plates (i.e., the foramen magnum).…”

Craniosynostosis

“…Although bicoronal synostosis is most common, Crouzon syndrome can present with late-onset pansynostosis. 18,19 It is important to be aware of this possibility in a child with a crouzonoid appearance, because apparently mild distortion of the skull shape may mask the presence of raised ICP. The association of crouzonoid facies with acanthosis nigricans is caused by a specific FGFR3 mutation (see below).…”

Progressive postnatal pansynostosis: an insidious and pernicious form of craniosynostosis

“…2 Hoefkens and coworkers documented PPP in 9 of 73 patients with Crouzon syndrome. 7 Affected patients had absent or mild clinical features, such as exorbitism and midfacial retrusion, in early infancy that appeared to progress with the onset of craniosynostosis. The authors referred to these patients as a "postnatally expressed subtype" of Crouzon, a finding reportedly discussed by Dr. Tessier.…”

“…Unlike more common forms of craniosynostosis, this entity typically manifests as a normally proportioned, albeit smaller than average, head shape. 2,7,10,11 The muted effect on calvarial form is attributable to the latent timing of sutural closure, usually occurring in the first 2 years of life. The majority of patients have an associated syndrome-Crouzon syndrome being most common 2,11 -but the characteristic craniofacial features can be subtle and easily overlooked.…”