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

Catherine A. de Planque MD1, Steven A. Wall MBBCh, FRCS, FRCPCH, FCS(SA)Plast2, Louise Dalton DClinPsych2, Giovanna Paternoster MD3, Éric Arnaud MD3, Marie-Lise C. van Veelen MD, PhD1, Sarah L. Versnel MD, PhD1, David Johnson MA, BM, BCh, DM, FRCS2, Jayaratnam Jayamohan MBBS, BSc, FRCS(SN)2, and Irene M. J. Mathijssen MD, PhD, MBA-H1
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  • 1 Dutch Craniofacial Centre, Department of Plastic and Reconstructive Surgery and Hand Surgery, Erasmus Medical Centre Sophia Children’s Hospital, University Medical Centre Rotterdam, Rotterdam, The Netherlands;
  • | 2 Craniofacial Unit, Department of Plastic and Reconstructive Surgery, John Radcliffe Hospital, Oxford, United Kingdom; and
  • | 3 Craniofacial Unit, Department of Pediatric Neurosurgery, Hôpital Necker-Enfants Malades, Paris, France
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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.

ABBREVIATIONS

CAN = Crouzon syndrome with acanthosis nigricans; ETV = endoscopic third ventriculostomy; FMD = foramen magnum decompression; FOHR = fronto-occipital horn ratio; FR = France; ICH = intracranial hypertension; NL = Netherlands; OAHI = obstructive apnea-hypopnea index; OSA = obstructive sleep apnea; UK = United Kingdom; VP = ventriculoperitoneal.

Image from Mavridis et al. (pp 404–415).

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