[P3-67] Familial infantile spasms caused by novel IQSEC2 mutation
X-linked infantile spasms are very rare. Here we report two cases of familial infantile spasms caused by IQSEC2 gene de novo missense mutation. They are brothers born in a south province of China. The clinical course was very similar in the two boys. They both had an uneventful pregnancy and delivery. At the age of 6 months they developed flexor spasms and a hypsarrhythmic EEG pattern. Early development was normal but mental retardation occurred after the onset of the disease. Brain MRI of them was normal. Both patients responded promptly to ACTH, but the symptoms of younger brother relapsed two months later. After treatment failure of several anti-epileptic drugs, the spasms of the younger brother were finally controlled by the ketogenic diet. Following the control of disease, the EEG was normalized and they both experienced remarkable improvement in development. Gene sequencing revealed that both patients carried a novel c.392G>C mutation in IQSEC2 located in Xp11.22, leading to a p.Arg131Pro substitution and probably protein dysfunction. The mother was identified as a heterozygous mutation carrier. The IQSEC2 gene plays a significant role in the maintenance of brain homeostasis. Besides intellectual disability, mutations in IQSEC2 can also lead to seizures, autistic-behavior, psychiatric problems, developmental delay and multiple malformations. To our knowledge, this is the first report of pure familial infantile spasms caused by IQSEC2 mutation. This report expanded on the mutational spectrum of IQSEC2 gene and we suggest IQSEC2 mutations should be taken into consideration in boys with otherwise unexplained infantile spasms.