Alagille syndrome (AGS) is an autosomal dominant multisystem disorder caused primarily by mutations in the JAG1 gene and, less commonly, in the NOTCH2 gene. The syndrome manifests predominantly with hepatic and cardiac involvement, but also includes a range of neuroanatomical and neurosurgically relevant abnormalities.
For neurosurgeons, AGS is particularly significant because of its cerebrovascular and skeletal features, 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
Mutation in the Notch signaling pathway leads to impaired organ development. Of particular relevance to neurosurgery is involvement of:
Cerebral vessels: dysplasias, stenoses, and Aneurysms[^2].
Skull and spine: skeletal anomalies
Neurosurgically relevant manifestations
Cerebrovascular anomalies
Patients with Alagille syndrome have an increased prevalence of:
Intracranial aneurysms
Moyamoya-like changes
Arterial stenoses or dilatations
Skull and spinal anomalies
Affected individuals frequently exhibit skeletal changes[^3], some of which are neurosurgically relevant:
Butterfly vertebrae
Anomalies of the craniocervical junction