Department of Prenatal Diagnosis Medical Center, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Department of Pediatrics, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Medicine (Baltimore). 2023 Feb 17;102(7):e33014. doi: 10.1097/MD.0000000000033014.
Lissencephaly (LIS) is a rare and serious cortical malformation characterized by a smooth or nearly smooth brain surface. With the progress of molecular genetics, platelet-activating factor acetylhydrolase brain isoform Ib is the most frequent type during the fetal period. Here, we report an infant with LIS who was missed although undergoing prenatal diagnosis. We aim to share our experiences and lessons.
A 2-month-old male infant presented recurrent convulsions. Karyotype and copy number variation sequencing were conducted to be normal at the 23-week gestation because of bipedal varus and ventricular septal defect (2.3 mm). After birth, he suffered from epilepsy confirmed by video electroencephalogram exam, meanwhile, computed tomography and magnetic resonance imaging revealed pachygyria. The infant was diagnosed with LIS carrying a de-novo mutation c.817 C > T (p.Arg273 Ter,138) in exon 8 of platelet-activating factor acetylhydrolase brain isoform Ib (NM_000430) detected by whole-exome sequencing.
Based on the clinical characteristics, imaging, and genetic test findings, the infant was diagnosed with LIS.
The patient was treated with topiramate and dose was adjusted according to the seizure frequency.
The infant had recurrent seizures. The muscle tone of his extremities increased, and he could not look up or turn over actively at the age of 6 months.
Comprehensive evaluation of a multi-disciplinary team should be recommended for patients with epilepsy and cerebral hypoplasia. Individuals with LIS during the fetal period might be missed due to atypical features. In fetuses with structural abnormalities, if karyotype and copy number variation sequencing are both normal, whole-exome sequencing may be an effective complementary means to detect pathogenic variants.
无脑回畸形（LIS）是一种罕见且严重的皮质畸形，其特征为脑表面光滑或几乎光滑。随着分子遗传学的进步，血小板激活因子乙酰水解酶脑型 Ib 是胎儿期最常见的类型。在此，我们报告了一例 LIS 婴儿，尽管进行了产前诊断，但仍被漏诊。我们旨在分享我们的经验和教训。
一名 2 个月大的男性婴儿反复出现抽搐。由于双足内翻和室间隔缺损（2.3mm），在 23 孕周时进行了染色体核型和拷贝数变异测序，结果均正常。出生后，他患有癫痫，经视频脑电图检查证实，同时 CT 和磁共振成像显示巨脑回。该婴儿携带血小板激活因子乙酰水解酶脑型 Ib（NM_000430）外显子 8 中 c.817 C > T（p.Arg273 Ter，138）的新生突变，经全外显子组测序检测，被诊断为 LIS。
根据临床特征、影像学和基因检测结果，该婴儿被诊断为 LIS。
患儿接受托吡酯治疗，并根据癫痫发作频率调整剂量。
该婴儿反复出现癫痫发作。他四肢的肌张力增加，6 个月大时无法主动抬头或翻身。
对于癫痫和脑发育不良的患者，应推荐多学科团队进行综合评估。在胎儿期有 LIS 表现的患者可能因特征不典型而被漏诊。在结构异常的胎儿中，如果染色体核型和拷贝数变异测序均正常，全外显子组测序可能是检测致病变异的有效补充手段。
