Craniosynostosis as a cause of intracranial hypertension in Alagille syndrome: a case series of 6 consecutive pediatric patients

Objective: Craniosynostoses are an underrecognized cause of intracranial hypertension (ICH), especially when associated with congenital syndromes. Alagille syndrome (ALGS) is a multisystem disorder with typical facial features and hepatobiliary, cardiac, vascular, skeletal, and ocular manifestations. The occurrence of craniosynostosis in ALGS is rare and can be associated with chronic ICH, requiring craniofacial surgery to increase the intracranial volume. The authors report a series of 6 patients with ALGS with craniosynostosis and discuss their neurosurgical management.

Methods: The authors included all patients with ALGS and craniosynostosis assessed in their national reference center between 2012 and 2024. They collected the following parameters: date of birth; sex; JAG1 mutation; hepatobiliary, cardiac, vascular, skeletal and ocular symptoms; type of craniosynostosis; presence of papilledema; head circumference; type of surgery (if needed); and clinical outcome.

Results: The 6 patients had a median age of 6 years at referral (range 15 months-6 years). Four patients presented with a history of ICH and papilledema. Craniofacial CT scans showed the fusion of all sutures (coronal, sagittal, and lambdoid) in 2 patients; bicoronal plus bilambdoid synostosis in 1 patient; and sagittal plus bilambdoid synostosis 1 patient. All patients required biparietal floating craniotomies, leading to prompt improvement of papilledema. Two patients without a history of ICH presented with single-suture synostosis without papilledema (anterior plagiocephaly and scaphocephaly).

Conclusions: The authors report single-suture and multisuture craniosynostosis associated with ALGS and its association with chronic ICH. They suggest systematic screening for craniosynostosis in patients with ALGS and papilledema to avoid unrecognized chronic ICH.