Huguenard Anna L, Johnson Gabrielle W, Desai Rupen R, Osbun Joshua W, Dacey Ralph G, Braverman Alan C
1Department of Neurosurgery, Washington University in St. Louis; and.
2Cardiovascular Division, Department of Medicine, Washington University in St. Louis, Missouri.
J Neurosurg. 2022 Oct 28;138(5):1385-1392. doi: 10.3171/2022.9.JNS221373. Print 2023 May 1.
Loeys-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.
This 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.
Eighty-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).
CM-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.
洛伊斯 - 迪茨综合征（LDS）是一种罕见的常染色体显性遗传病，其特征包括主动脉、主动脉分支和颅内动脉的动脉瘤；骨骼和皮肤异常；以及颅面畸形。既往有作者报道，较高的颅面严重程度指数（CFI）评分表明颅面异常更严重，与主动脉瘤病理的严重程度相关。然而，LDS患者的综合征特征与颅内动脉瘤形成之间的关联尚未确定。在本研究中，作者评估了一个大型LDS队列中表型异常、颅面特征和I型 Chiari 畸形（CM-I）的发生率，并探讨颅内动脉瘤发生的可能危险因素。
这是一项对2010年至2022年期间在圣路易斯华盛顿大学医学院马凡综合征与主动脉病变中心就诊的所有LDS患者进行的回顾性队列研究。查阅病历以获取人口统计学、临床和影像学数据。确定颅面、骨骼和皮肤病变的患病率。进行二元逻辑回归以确定颅内动脉瘤形成的可能危险因素。
分析纳入了81例有完整病历和颅内血管成像的患者，其中18例（22.2%）至少有1个颅内动脉瘤。患者常表现出LDS典型的薄或半透明皮肤、面团样皮肤质地、眼距过宽、悬雍垂异常和关节活动过度。CM-I很常见，在7.4%的患者中出现。重要的是，有颅内动脉瘤的患者比没有颅内动脉瘤的患者更易发生CM-I（分别为22.2%和3.2%）。有可用数据的队列中CFI评分的平均值为1.81，携带TGFBR1或TGFBR2致病变异的患者平均值较高（分别为2.05和3.30），而携带SMAD3、TGFB2或TGFB3致病变异的患者平均值较低（CFI < 1）。有或无颅内动脉瘤的患者之间未观察到CFI有显著差异（2.06对1.74，p = 0.61）。
在LDS患者中，与颅内动脉瘤存在显著相关的是CM-I，而非CFI。对所有LDS患者进行颅内动脉瘤监测至关重要，不应局限于那些具有严重表型的患者。需要进行长期监测研究以确定颅面异常与颅内动脉瘤不良后果（生长、干预或破裂）之间是否存在相关性。
