Alagille syndrome (AGS) is an autosomal dominant multisystem disorder primarily caused by mutations in the JAG1 gene and, less commonly, in the NOTCH2 gene. The syndrome primarily manifests with hepatic and cardiac involvement, but also exhibits a range of neuroanatomical and neurosurgically relevant abnormalities.
For neurosurgeons, AGS is particularly significant because of its cerebrovascular and skeletal abnormalities, which can substantially modify the risk profile of procedures involving the head and Spine.
Epidemiology
The prevalence of Alagille syndrome is approximately 1:70,000[^1].
Pathophysiology
Mutations in the Notch signaling pathway lead to impaired organ development. Of particular neurosurgical relevance is involvement of:
Cerebral vessels: dysplasia, stenoses, and Aneurysms[^2].
Skull bones and spine: skeletal anomalies
Neurosurgically relevant manifestations
Cerebrovascular anomalies
Patients with Alagille syndrome have an increased prevalence of:
Skull and spinal abnormalities
Affected individuals frequently have skeletal abnormalities[^3], some of which are neurosurgically relevant: