University Children's Hospital of Heidelberg, Germany.
Am J Med Genet C Semin Med Genet. 2010 Feb 15;154C(1):102-8. doi: 10.1002/ajmg.c.30243.
Holoprosencephaly (HPE) is the most common structural malformation of the developing forebrain in humans. The HPE phenotype is extremely variable and the etiology is heterogeneous. Among a variety of embryological toxins that can induce HPE, inhibitors, and other pertubations of cholesterol biosynthesis have been shown to be important factors, most likely because cholesterol is required in the Sonic hedgehog signaling cascade. Decreased levels of maternal cholesterol during pregnancy increase the risk for preterm delivery, but they are not associated with congenital malformations. However, if the fetus is affected by an inborn error of endogenous cholesterol synthesis, a reduction of maternal cholesterol concentration and cholesterol transport over the placenta aggravates the phenotypic expression. Exposure to lipophilic statins in early pregnancy may be associated with a substantial risk for structural CNS defects.
前脑无裂畸形(HPE)是人类发育中前脑最常见的结构畸形。HPE 的表型极其多样,病因具有异质性。在各种可能导致 HPE 的胚胎毒素中,胆固醇生物合成的抑制剂和其他干扰物已被证明是重要因素,这很可能是因为胆固醇是 Sonic hedgehog 信号级联反应所必需的。怀孕期间母体胆固醇水平降低会增加早产的风险,但与先天性畸形无关。然而,如果胎儿受到内源性胆固醇合成的先天性错误的影响,那么母体胆固醇浓度和胆固醇在胎盘内的转运减少会加重表型表达。在妊娠早期接触亲脂性他汀类药物可能与结构性中枢神经系统缺陷的显著风险相关。