Bilateral schizencephaly and open-clip schizencephaly present severe clinical manifestion and refractory epilepsy [7,12]. However, unilateral closed-lip schizencephaly is always asymptomatic and be diagnosed at adolescent. In addition, closed lip clefts had less treatment-resistant seizures and better prognosis [13]. Camila F Lopes et al [14] found the incidence of treatment-resistant seizures in closed-lip schizencephaly is 15% while the incidence of treatment-resistant seizures in open-lip schizencephaly is 54%. Unilateral closed-lip schizencephaly presents milder clinical fetures and has a better developmental outcome [14-15]. However, in this study, a case of unilateral closed-lip schizencephaly combined with hypomyelination was diagnosed in neonate and became refractory epilepsy, leading to poor prognosis. Microtubule dysfunction is one of the mechanisms of schizencephaly and hypomyelination. Microtubules can regulate neuronal proliferation, nerve cells migration and cortical laminar organization [16]. Cerebral cortex cells migration abnormality is importantmechanism of schizencephaly. In addition, microtubules are crucial for the hypomyelination by affecting the development of oligodendrocytes [17]. β-tubulin, which is encoded by tubulin beta (TUBB), dimerizes with α-tubulin as the major subunit of microtubules. In recent years, an increasing number of studies have reported that schizencephaly and hypomyelination both are resulted from the mutations of tubulin genes (TUBB2B, TUBB4A, TUBA1A, TUBB3, and so on) [18-21]. In this study, whole exon sequencing was performed in this patient and her parents. The GPSM2 (G-protein signalling modulator 2) mutation NM_013296.5:exon14: c.1789T>C (p.Phe597Leu) was found in this case. The GPSM2 c.1789T>C mutation is a harmful mutation predicted by sorting intolerant from tolerant (SIFT), Polyphen2_HDIVMutation Taster. GPSM2 can regulate cerebral cortical migration by affecting microtubule stabilities during neurogenesis, neuronal migration and connections with other neurons [22-27]. In previous study, GPSM2 mutation was found in polymicrogyria, one of the cerebral malformations [24, 28]. Microtubule dysfunction is one of the mechanisms of neuronal malformation and hypomyelination. Therefore, we hypothesize GPSM2 c.1789T>C mutation regulates the dynamics of microtubules.