<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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 involv pmc Childs Nerv Syst Childs Nerv Syst 365 springeropen Child's Nervous System 0256-7040 1433-0350 pmc-is-collection-domain yes pmc-collection-title Springer PMC13149708 PMC13149708.1 13149708 13149708 42091709 10.1007/s00381-026-07308-7 7308 1 Review Cranial nerves involvement in craniosynostosis: a systematic review http://orcid.org/0000-0002-5130-3971 Manara, Renzo 1 2 http://orcid.org/0000-0002-2601-9055 Tietze Anna 3 Faggin Roberto 4 http://orcid.org/0000-0001-9722-7145 Valeggia Silvia silvia.valeggia@unipd.it 1 10 http://orcid.org/0000-0003-2282-0256 Tarnow Peter 5 http://orcid.org/0000-0002-5037-8568 Trevisi Patrizia 6 http://orcid.org/0000-0002-2491-7783 De Filippis Cosimo 7 http://orcid.org/0000-0002-1675-9922 Mathijssen Irene M. Background 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 can be affected with a possible dramatic impact on the overall development and quality of life of the child. Since our knowledge on this topic is mainly driven by anecdotal case reports and sparse case series and studies, we performed a thorough literature review on cranial nerve involvement in craniosynostosis. Optic nerve atrophy was more common in Apert (100% of patients), Crouzon (83.3%), For these reasons, any corrective surgery of strabismus should be planned after a thorough evaluation of the orbit including all muscle position and shape (Fig. 3 B). Finally, some anecdotal MRI-proven cases of VI nerve aplasia have been reported suggesting that strabismus may also be caused by abnormal nerve development [ 8 ]. Nowadays, high-resolution T2 MR images can easily show even with 1.5 T scanners the cisternal segment of the III and VI cranial nerves, while the IV cranial nerve is reliably investigated only with 3 T MR scanners. So far, no imaging or functional data are available regarding the coexistence of nerve and muscle aplasia or an alternative muscle innervation in case of nerve aplasia. Acquired ophthalmoplegia/ocular muscle dysfunction Acquired abducens and trochlear or even oculomotor nerve palsy [ 48 ] might be caused by downward displacement of the brainstem due to increased intracranial pressure requiring prompt corrective surgery (e.g., ventricular shunting [ 49 ] or cranial vault remodeling [ 50 ]). The above-mentioned syndrome, also called cerebello-trigeminal-dermal dysplasia, was first characterized in 1979 and encompasses ataxia, trigeminal hypoesthesia, bilateral temporo-parietal alopecia and brachycephaly, while the MRI shows rhombencephalosynapsis with pons-vermis fusion and trigeminal nerve hypoplasia [ 55 ]. A CT study showed the absence of the foramina rotunda, suggesting the aplasia of some trigeminal (sensory) branches [ 56 ]. So far, about 60 cases have been reported, but the syndrome is likely to be underrecognized [ 57 , 58 ]. However, differences among syndromes or specific suture involvement prevent any generalization. Therefore, dedicated functional/clinical tests and imaging protocols should be included in the routine management of patients in order to better characterize different craniosynostosis types and provide specific guidelines for the assessment and the proper treatment of cranial nerve–related deficits. Considering the rarity of many craniosynostosis types, a joint effort across referral centers is warranted to promote our knowledge. Supplementary Information Below is the link to the electronic supplementary material. ESM 1 (DOCX.19.6 KB)