皮质发育(MCD)畸形是一组影响人类皮质正常发育的疾病,是儿童精神运动发育延迟和癫痫的重要原因。脑白质(光滑的大脑)构成了大脑畸形的主要群体。微管有助于神经元细胞的迁移。微管蛋白基因α-微管蛋白(TUBA)缺陷,β-微管蛋白(TUBB),和γ-微管蛋白(TUBG)导致神经元迁移缺陷。这组疾病被称为“微管病”。“与导致间脑畸形有关的重要基因是LIS1,XLIS,和TUBA1A基因。最近,TUBG1基因的突变与之相关。这里,我们报告了一个一岁半的女孩,患有全球发育迟缓,小头畸形,婴儿发作性癫痫,癫痫性痉挛,畸形,和马达标志。没有明显的出生史。神经影像学(MRI)显示宽厚的回和沟数减少,提示间脑/厚脑频谱。心室扩张,没有注意到灰质异位症。睡眠脑电图显示多灶性癫痫样放电。该儿童接受了多种抗癫痫药物(ASM)治疗。基因测试,整个外显子组测序,是为了确定MCD的病因。鉴定了TUBG1基因外显子6中的杂合错义变异,并报告为未知意义的“变异”。“尽管如此,因为基因型与患者的临床表型相匹配,被认为具有临床意义.因此,对TUBG1突变相关的皮质畸形(间脑畸形/厚脑畸形)合并小头畸形和早发性癫痫进行了完整诊断.TUBG1突变在大多数情况下是从头的,但建议家长测试。这些患者的父母需要咨询产前检查的必要性和疾病对兄弟姐妹的风险。由于难治性癫痫发作,此类病例的总体预后较差,物理限制,智力残疾。
Malformations of cortical development (MCD) are a group of disorders affecting the normal development of the human cortex and are significant causes of delay in psychomotor development and epilepsy in children. Lissencephaly (smooth brain) forms a major group of brain malformations. Microtubules help in the migration of neuronal cells. Defect in tubulin gene alpha-tubulin (TUBA), beta-tubulin (TUBB), and gamma-tubulin (TUBG) leads to defective neuronal migration. This group of disorders is termed as \"tubulinopathies.\" The important genes implicated in causing lissencephaly are LIS1, XLIS, and TUBA1A gene. Recently, a mutation in the TUBG1 gene is associated with it. Here, we report a one-and-a-half-year-old girl with global developmental delay,
microcephaly, infantile-onset epilepsy, epileptic spasms, dysmorphism, and motor signs. There was no significant birth history. Neuroimaging (MRI) showed a broad thick gyri and a decreased number of sulci suggestive of lissencephaly/pachygyria spectrum. There was dilatation of the ventricles, and no grey matter heterotopia was noted. Sleep EEG showed multifocal epileptiform discharges. The child was treated with multiple anti-seizure medicines (ASMs). A genetic test, whole exome sequencing, was done to determine the etiology of MCD. A heterozygous missense variation in exon 6 of the TUBG1 gene was identified and reported as a \"variant of unknown significance.\" Still, because the genotype matched with the clinical phenotype of the patient, it was considered clinically significant. Therefore, a complete diagnosis of TUBG1 mutation-associated cortical malformation (lissencephaly/pachygyria) with
microcephaly and early-onset epilepsy was established. TUBG1 mutation is de novo in most cases, but parental testing is recommended. The parents of such patients need to be counseled about the need for prenatal testing and the risk of the disease to siblings. The overall prognosis in such cases is poor because of refractory seizures, physical limitations, and intellectual disability.