Dang Do An N, Baker Eva H, Warren Katherine E, Bianconi Simona E, Porter Forbes D
Division of Translational Research, Eunice Kennedy Shriver National Institute of Human Development (NICHD), National Institutes of Health, Bethesda, Maryland.
Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland.
Am J Med Genet A. 2018 Feb;176(2):386-390. doi: 10.1002/ajmg.a.38563. Epub 2017 Dec 11.
Smith-Lemli-Opitz syndrome (SLOS) is a metabolic disorder caused by an inborn error of cholesterol synthesis that affects the development of many organ systems. Malformations in the central nervous system typically involve midline structures and reflect abnormal growth and differentiation of neurons and supporting cells. Despite these defects in central nervous system development, brain tumor formation has only rarely been reported in association with SLOS. We present three individuals with SLOS and lesions in the basal ganglia or brainstem detected by MRI that were concerning for tumor formation. However, the individuals' clinical and neurological course remained stable, and the lesions regressed after several years. These lesions have similarities to spongiotic changes observed in individuals with neurofibromatosis type 1 (NF1). Notably, impaired activity of small GTPases is present in both SLOS and NF1, perhaps giving mechanistic insight into the formation of these lesions.
史密斯-莱姆利-奥皮茨综合征（SLOS）是一种由胆固醇合成先天性缺陷引起的代谢紊乱疾病，会影响多个器官系统的发育。中枢神经系统的畸形通常累及中线结构，反映了神经元和支持细胞的异常生长与分化。尽管中枢神经系统发育存在这些缺陷，但仅有极少关于SLOS合并脑肿瘤形成的报道。我们报告了三名患有SLOS的个体，通过MRI检测发现其基底神经节或脑干有病变，疑似肿瘤形成。然而，这些个体的临床和神经病程保持稳定，病变在数年后消退。这些病变与1型神经纤维瘤病（NF1）患者中观察到的海绵状改变相似。值得注意的是，SLOS和NF1中均存在小GTP酶活性受损的情况，这或许能为这些病变的形成提供机制上的见解。
