Patients with Alagille syndrome (ALGS) can present with a wide variety of craniospinal manifestations, which may influence prognosis. Although they are less well-known and prevalent than other clinical manifestations—such as cholestasis, cardiac defects, skeletal and ophthalmologic abnormalities, and characteristic facial features—healthcare providers should be aware of their existence, the authors of a new study wrote.

Cerebrovascular anomalies in patients with ALGS include aneurysms, dolichoectasia, arterial stenosis, Moyamoya syndrome, agenesis of the internal carotid artery, persistent falcon sinus, and cerebral vein tortuosity.

“In particular, acute complications of vascular stenosis and rupture of aneurysms can cause ischemic strokes and hemorrhages, respectively. Therefore, arterial screening with unenhanced brain [magnetic resonance angiography] is suggested in patients with ALGS,” D’Amico et al advised in a recent review article published in The British Journal of Radiology.

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The estimated prevalence of intracranial arterial and venous anomalies in patients with ALGS is 30% to 40%. Strokes and intracranial hemorrhage occur in about 14% and 14% to 16% of ALGS patients, respectively. The predisposition to develop vascular abnormalities might be, at least in part, associated with the Notch signaling pathway, which is vital for the angiogenic process.

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Skull malformations are the second most common bone abnormality in patients with ALGS, with an estimated prevalence of 0.9%. These include craniosynostosis, clivus hypoplasia, and foveola pharyngica.

About a third of ALGS patients present with Chiari 1 malformation. In addition, idiopathic intracranial hypertension has been reported in some patients.

Vertebral anomalies are the most frequent skeletal malformation in patients with ALGS, with an estimated prevalence of 51% to 60%. Almost half of the patients are affected by multiple alterations. Vertebral anomalies include butterfly vertebra, hemivertebra, and segmentation anomalies.

Other spine malformations, such as anomalies of the craniocervical junction, have also been observed in patients with ALGS.

Cerebral midline malformations and temporal bone anomalies are rarer events. Midline malformations include corpus callosum thinning, hypoplasia of the splenium and the isthmus of the corpus callosum, isolated agenesis of the septum pellucidum, and bilateral incomplete hippocampal inversion. Temporal bone anomalies include agenesia/hypoplasia of the posterior semicircular canals and cochlear hypoplasia.

As concluded by D’Amico et al, “knowledge of the aforementioned neuroradiological findings can further corroborate clinical suspicion of ALGS, thus improving diagnostic work-up.”


D’Amico A, Perillo T, Cuocolo R, et al. Neuroradiological findings in Alagille syndrome. Br J Radiol. Published online October 5, 2021. doi:10.1259/bjr.20201241