Cranial nerves involvement in craniosynostosis: a systematic review

The improved management of craniosynostosis has let emerge concomitant anatomical, functional and clinical features that are frequently faced later in life (especially by syndromic patients) and might variably encompass the cranial nerves due to stenosis of bone foramina, abnormal intracranial pressure, or anomalous gene-driven development. Clinical consequences vary according to the affected nerves, the severity and the pathogenesis of nerve involvement but also might depend on early appropriate treatment. Vision, smell and hearing, but also feeding, swallowing and facial mimic or esthesia might be affected with a possible dramatic impact on the overall development of the child and on its quality of life.

A systematic literature review regarding cranial nerves involvement in craniosynostosis was performed, including case series and case reports. According to PRISMA criteria, PubMed and Scopus were searched up to February 2025 by two independent reviewers. Relevant English-language case reports and case series were included, while duplicate or aggregated data were excluded. Reference lists were screened, and disagreements were resolved by consensus. Sixty-three papers were considered. Data extracted from the papers were subjected to statistical analysis only for the optic nerve, owing to the paucity of data concerning the other cranial nerves.

Optic nerve involvement was reported in 140 patients (44 papers) and included papilledema (69 patients), optic nerve atrophy (69 patients), and optic nerve hypoplasia (5 patients). Visual function was reduced in 65 patients, normal in 9. In sixty-eight patients (49%) an underlying syndrome was specified, most commonly Crouzon syndrome (27/68, 39.7%) and Apert syndrome (23/68, 33.8%); 5/140 (4%) had a secondary craniosynostosis. When reported, there was a prevalence of male sex (43/67 males; 65.2%), bilateral optic nerve involvement (66/78 patients; 84.6%) and multisutural involvement (37/52; 71.2%). Other upper cranial nerve involvement (III, IV, VI) was more frequently reported in the management of craniosynostosis children. Some cranial nerves were part of specific syndromes (e.g., I or V) or were involved during surgery. Finally, very scarce literature reports inferior cranial nerve involvement even though posterior cranial fossa neural impingement is a common complication in syndromic forms.

Cranial nerve involvement is common; it presents differences among syndromes and specific suture involvement but is still under-investigated in craniosynostosis. Guidelines for the assessment and the proper treatment of cranial nerve-related deficits are warranted, and a joint effort of referral centers is needed for overcoming the rarity of craniosynostosis forms.