Nervous system involvement in Pfeiffer syndrome

Childs Nerv Syst. 2021 Feb;37(2):367-374. doi: 10.1007/s00381-020-04934-7. Epub 2020 Oct 20.


Pfeiffer syndrome (PS) is a rare autosomal dominant craniofacial disorder characterized by primary craniosynostosis, midface hypoplasia, and extremities' abnormalities including syndactyly. The purpose of this article was to review the current knowledge regarding how PS affects the nervous system. Methodologically, we conducted a systematic review of the existing literature concerning involvement of the nervous system in PS. Multiple-suture synostosis is common, and it is the premature fusion and abnormal growth of the facial skeleton's bones that cause the characteristic facial features of these patients. Brain abnormalities in PS can be primary or secondary. Primary anomalies are specific developmental brain defects including disorders of the white matter. Secondary anomalies are the result of skull deformity and include intracranial hypertension, hydrocephalus, and Chiari type I malformation. Spinal anomalies in PS patients include fusion of vertebrae, "butterfly" vertebra, and sacrococcygeal extension. Different features have been observed in different types of this syndrome. Cloverleaf skull deformity characterizes PS type II. The main neurological abnormalities are mental retardation, learning difficulties, and seizures. The tricky neurological examination in severely affected patients makes difficult the early diagnosis of neurological and neurosurgical complications. Prenatal diagnosis of PS is possible either molecularly or by sonography, and the differential diagnosis includes other craniosynostosis syndromes. Knowing how PS affects the nervous system is important, not only for understanding its pathogenesis and determining its prognosis but also for the guidance of decision-making in the various critical steps of its management. The latter necessitates an experienced multidisciplinary team.

Keywords: Brain anomalies; Craniosynostosis; Fibroblast growth factor receptor; Intracranial hypertension; Neurological findings; Pfeiffer syndrome.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Acrocephalosyndactylia* / complications
  • Acrocephalosyndactylia* / diagnostic imaging
  • Brain
  • Craniosynostoses* / diagnostic imaging
  • Facial Bones
  • Humans
  • Hydrocephalus*