Moerike Shelley, Pantzar J Tapio, De Sa Derek
Department of Pathology and Laboratory Medicine, Children's and Women's Health Centre of British Columbia, 4480 Oak Street, Vancouver, British Columbia, Canada V6H 3V4.
Pediatr Dev Pathol. 2002 Jul-Aug;5(4):405-9. doi: 10.1007/s10024-001-0258-0. Epub 2002 May 21.
Isotretinoin can be teratogenic, affecting many tissues, including the ear. However, there are only two histopathologic studies of the temporal bone in affected humans, and neither describes the findings in early gestation. We had the opportunity to study both temporal bones in each of two fetuses (22 and 24 weeks) exposed to isotretinoin in early gestation. One of the fetuses had a dilated IVth ventricle and a hypoplastic cerebellar vermis, while no dysmorphic features were seen in the other. In both infants the external ears were not noticeably abnormal. Histologically, anomalies of the middle ear included medial deviation of the malleus, forward displacement of the incus, and a small tympanic cavity (4/4); unilateral absence of the stapes (1/4); single "columella" crus and hypoplastic footplate (3/4); and unilateral dehiscence of the facial canal in one infant. Autolysis limited the examination of the labyrinth, but there was reduction in the number of cochlear spirals, and dilatation of the saccule in both infants. Anomalies of the middle and inner ear can be present without anomalies of the external ear or the central nervous system, and may be found even after relatively short exposures. These anomalies are similar to those detected in experimental exposure to isotretinoin, and are consistent with altered expression of the goosecoid gene.
异维甲酸可致畸，影响包括耳部在内的许多组织。然而，仅有两项针对受影响人类颞骨的组织病理学研究，且均未描述妊娠早期的发现。我们有机会对两名在妊娠早期接触异维甲酸的胎儿（分别为22周和24周）的双侧颞骨进行研究。其中一名胎儿有第四脑室扩张和小脑蚓部发育不全，而另一名未发现畸形特征。两名婴儿的外耳均无明显异常。组织学上，中耳异常包括锤骨向内侧移位、砧骨向前移位以及鼓室较小（4/4）；镫骨单侧缺如（1/4）；单一“小柱”脚和发育不全的镫骨底板（3/4）；以及一名婴儿面神经管单侧裂开。自溶限制了对迷路的检查，但两名婴儿均有耳蜗螺旋数量减少和球囊扩张。中耳和内耳异常可在无外耳或中枢神经系统异常的情况下出现，甚至在接触时间相对较短后也可能被发现。这些异常与在异维甲酸实验性接触中检测到的异常相似，并且与鹅膏蕈氨酸基因表达改变一致。
