X-linked hypophosphatemic rickets: cases series and literature review with a focus on neurosurgical management


  • Federico Baronio Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di S. Orsola, Bologna - Italy https://orcid.org/0000-0003-3470-6880
  • Ferdinando Aliberti Department of Pediatric Neurosciences, Pediatric Neurosurgery Unit, Santobono-Pausilipon Children’s Hospital, Naples - Italy
  • Filomena Carfagnini Unit of Pediatric Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna - Italy
  • Giovanni Luigi Di Gennaro Pediatrics Orthopedics and Traumatology, IRCCS Istituto Ortopedico Rizzoli, Bologna - Italy https://orcid.org/0000-0002-5562-2339
  • Daniela Pasquali Endocrinology Unit, Department of Advanced Medical And Surgical Sciences, University of Campania “L. Vanvitelli”, Naples - Italy https://orcid.org/0000-0002-5674-635X
  • Rossella Santoro Multidisciplinary Department of Medical, Surgical and Dental Specialties, University of Campania “Luigi Vanvitelli”, Naples - Italy https://orcid.org/0000-0002-3985-2978
  • Giuseppe Toro Multidisciplinary Department of Medical, Surgical and Dental Specialties, Luigi Vanvitelli University of Campania, Naples, Italy
  • Mino Zucchelli IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna - Italia, Pediatric Neurosurgery https://orcid.org/0000-0002-7494-355X
  • Anna Grandone Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples - Italy https://orcid.org/0000-0002-6343-4768




Arnold-Chiari type 1 syndrome, Craniostenosis, Neurosurgical complications, X-linked hypophosphatemic rickets


X-linked hypophosphatemic rickets (XLH) is an X-linked dominant disease caused by mutations in the Phosphate-Regulating Endopeptidase X-Linked (PHEX) gene. Due to its rarity and the wide range of clinical manifestations, management of the disease can be challenging due to several associated clinical implications that may arise during follow-up. The neurological complications associated with XLH are the most severe and often less known, which lead to important comorbidities. With the aim of summarizing the available knowledge on neurosurgical intervention in patients with XLH, we present four emblematic cases with disorders requiring neurosurgical evaluation. Relevant diagnostic delay was seen in two of these cases, with another case demonstrating that complications requiring neurosurgery may be present even in patients with few symptoms. The last case stresses the need for care of adult patients who can present with undiagnosed comorbidities. We also carried out a narrative review on neurosurgical interventions in patients with XLH. Through case reports and a review of the literature, focus is placed on the role of the neurosurgeon in the management of patients with XLH. In fact, neurosurgical intervention can often provide stable outcomes for craniosynostosis and clinical improvement for symptoms related to spinal stenosis. Thus, the neurosurgeon can aid in optimizing management of patients with XLH and should be a member of both adult and pediatric multidisciplinary teams. Lastly, additional studies are needed to determine if the early use of burosumab in infants can help to avoid complications in the long term.


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How to Cite

Baronio, F., Aliberti, F., Carfagnini, F., Di Gennaro, G. L., Pasquali, D., Santoro, R., Toro, G., Zucchelli, M., & Grandone, A. (2023). X-linked hypophosphatemic rickets: cases series and literature review with a focus on neurosurgical management. AboutOpen, 10(1), 35–42. https://doi.org/10.33393/ao.2023.2513



Brief report


Received 2022-10-26
Accepted 2023-02-13
Published 2023-03-07