Clinical signs, interventions, and treatment course of three different treatment protocols in patients with Crouzon syndrome with acanthosis nigricans

J Neurosurg Pediatr. 2021 Aug 13;28(4):425-431. doi: 10.3171/2021.2.PEDS20933.


Objective: Crouzon syndrome with acanthosis nigricans (CAN) is a rare and clinically complex subtype of Crouzon syndrome. At three craniofacial centers, this multicenter study was undertaken to assess clinical signs in relation to the required interventions and treatment course in patients with CAN.

Methods: A retrospective cohort study of CAN was performed to obtain information about the clinical treatment course of these patients. Three centers participated: Erasmus Medical Centre, Rotterdam, the Netherlands; John Radcliffe Hospital, Oxford, United Kingdom; and Hôpital Necker-Enfants Malades, Paris, France.

Results: Nineteen patients (5 males, 14 females) were included in the study. All children were operated on, with a mean of 2.2 surgeries per patient (range 1-6). Overall, the following procedures were performed: 23 vault expansions, 10 monobloc corrections, 6 midface surgeries, 11 foramen magnum decompressions, 29 CSF-diverting surgeries, 23 shunt-related interventions, and 6 endoscopic third ventriculostomies, 3 of which subsequently required a shunt.

Conclusions: This study demonstrates that patients with the mutation c.1172C>A (p.Ala391Glu) in the FGFR3 gene have a severe disease trajectory, requiring multiple surgical procedures. The timing and order of interventions have changed among patients and centers. It was not possible to differentiate the effect of a more severe clinical presentation from the effect of treatment order on outcome.

Keywords: Crouzon syndrome with acanthosis nigricans; FGFR3; craniofacial; craniosynostosis.

Publication types

  • Multicenter Study

MeSH terms

  • Acanthosis Nigricans / complications
  • Acanthosis Nigricans / genetics
  • Acanthosis Nigricans / surgery*
  • Brain / diagnostic imaging
  • Child
  • Child, Preschool
  • Clinical Protocols
  • Cohort Studies
  • Craniofacial Abnormalities / surgery
  • Craniofacial Dysostosis / complications
  • Craniofacial Dysostosis / genetics
  • Craniofacial Dysostosis / surgery*
  • Decompression, Surgical
  • Female
  • Foramen Magnum / surgery
  • France
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Mutation / genetics
  • Netherlands
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • United Kingdom
  • Ventriculostomy


  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3

Supplementary concepts

  • Crouzon Syndrome With Acanthosis Nigricans