• Anna L Huguenard, Gabrielle W Johnson, Rupen R Desai, Joshua W Osbun, Ralph G Dacey, and Alan C Braverman.
• 1Department of Neurosurgery, Washington University in St. Louis; and.
• J. Neurosurg. 2023 May 1; 138 (5): 138513921385-1392.

ObjectiveLoeys-Dietz syndrome (LDS) is a rare autosomal dominant condition characterized by aneurysms of the aorta, aortic branches, and intracranial arteries; skeletal and cutaneous abnormalities; and craniofacial malformations. Previous authors have reported that higher craniofacial severity index (CFI) scores, which indicate more severe craniofacial abnormalities, correlate with the severity of aortic aneurysm pathology. However, the association between syndromic features and the formation of intracranial aneurysms in LDS patients has yet to be determined. In this study, the authors evaluate the incidence of phenotypic abnormalities, craniofacial features, and Chiari malformation type I (CM-I) in a large LDS cohort and explore possible risk factors for the development of intracranial aneurysms.MethodsThis was a retrospective cohort study of all patients with LDS who had been seen at the Marfan Syndrome and Aortopathy Center at Washington University School of Medicine in St. Louis in 2010-2022. Medical records were reviewed to obtain demographic, clinical, and radiographic data. The prevalence of craniofacial, skeletal, and cutaneous pathologies was determined. Bivariate logistic regression was performed to identify possible risk factors for the formation of an intracranial aneurysm.ResultsEighty-one patients with complete medical records and intracranial vascular imaging were included in the analysis, and 18 patients (22.2%) had at least 1 intracranial aneurysm. Patients frequently demonstrated the thin or translucent skin, doughy skin texture, hypertelorism, uvular abnormalities, and joint hypermobility typical of LDS. CM-I was common, occurring in 7.4% of the patients. Importantly, the patients with intracranial aneurysms were more likely to have CM-I (22.2%) than those without intracranial aneurysms (3.2%). The mean CFI score in the cohort with available data was 1.81, with higher means in the patients with the TGFBR1 or TGFBR2 disease-causing variants (2.05 and 3.30, respectively) and lower in the patients with the SMAD3, TGFB2, or TGFB3 pathogenic variants (CFI < 1). No significant CFI difference was observed in patients with or without intracranial aneurysms (2.06 vs 1.74, p = 0.61).ConclusionsCM-I, and not the CFI, is significantly associated with the presence of intracranial aneurysms in patients with LDS. Surveillance for intracranial aneurysms is essential in all patients with LDS and should not be limited to those with severe phenotypes. Long-term monitoring studies will be necessary to determine whether a correlation between craniofacial abnormalities and adverse outcomes from intracranial aneurysms (growth, intervention, or rupture) exists.

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