Division of Fetal and Transitional Medicine, Children's National Health System, Washington, District of Columbia; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia; Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia.
Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
Pediatr Neurol. 2019 May;94:64-69. doi: 10.1016/j.pediatrneurol.2018.12.009. Epub 2018 Dec 24.
Arrest of fetal brain development and the fetal brain disruption sequence describe a severe phenotype involving microcephaly, occipital bone prominence, and scalp rugae. Congenital disorders of glycosylation are a heterogeneous group of inherited disorders involved in glycoprotein and glycolipid biosynthesis, which can cause microcephaly and severe neurodevelopmental disability.
We report an example of fetal microcephaly diagnosed at 36 weeks' gestation with a history of normal fetal biometry at 20 weeks' gestation. Postnatal genetic testing was performed.
Fetal magnetic resonance imaging at 36 weeks' gestational age showed severe cortical thinning with a simplified gyral pattern for gestational age, ventriculomegaly, and agenesis of the corpus callosum. The fetal skull had a posterior shelf at the level of the lambdoid suture, characteristic of fetal brain disruption sequence. Postnatal brain magnetic resonance imaging found no brain growth during the interval from the fetal to postnatal study. The infant was found to have biallelic pathologic mutations in ALG11.
Arrest of fetal brain development, with image findings consistent with fetal brain disruption sequence, is a previously unreported phenotype of congenital microcephaly in ALG11-congenital disorder of glycosylation. ALG11-congenital disorder of glycosylation should be considered in the differential diagnosis of this rare form of congenital microcephaly.
胎儿脑发育停滞和胎儿脑破坏序列描述了一种严重的表型，涉及小头畸形、枕骨突出和头皮皱折。糖基化先天性疾病是一组涉及糖蛋白和糖脂生物合成的遗传性疾病，可导致小头畸形和严重的神经发育障碍。
我们报告了一例在 36 孕周时诊断为胎儿小头畸形的病例，该病例在 20 孕周时的胎儿生物测量正常。进行了产后基因检测。
36 孕周胎儿磁共振成像显示皮质严重变薄，脑回模式简单化，与胎龄相符，脑室扩大，胼胝体发育不全。胎儿颅骨在人字缝水平有后突，具有胎儿脑破坏序列的特征。产后磁共振成像发现从胎儿到产后研究期间脑没有生长。该婴儿被发现存在 ALG11 的双等位基因病理性突变。
胎儿脑发育停滞，影像学表现与胎儿脑破坏序列一致，是 ALG11-糖基化先天性疾病导致的先天性小头畸形的一种以前未报告的表型。在这种罕见的先天性小头畸形的鉴别诊断中，应考虑 ALG11-糖基化先天性疾病。
