A case of recurrent encephalopathy with SCN2A missense mutation

• Published in: Brain & development (Tokyo. 1979) 2015-06, Vol.37 (6), p.631-634
• Main Authors: Fukasawa, Tatsuya, Kubota, Tetsuo, Negoro, Tamiko, Saitoh, Makiko, Mizuguchi, Masashi, Ihara, Yukiko, Ishii, Atsushi, Hirose, Shinichi
• Format: Article
• Language: English
• Subjects: Brain - pathology; Brain - physiopathology; Brain Diseases - diagnosis; Brain Diseases - genetics; Brain Diseases - pathology; Brain Diseases - physiopathology; Diffusion Magnetic Resonance Imaging; Electroencephalography; Encephalopathy; Humans; Infant; Male; Mutation; Mutation, Missense; NAV1.2 Voltage-Gated Sodium Channel - genetics; Neurology; Recurrence; SCN2A
• ISSN: 0387-7604; 1872-7131
• DOI: 10.1016/j.braindev.2014.10.001

Abstract Voltage-gated sodium channels regulate neuronal excitability, as well as survival and the patterning of neuronal connectivity during development. Mutations in SCN2A , which encodes the Na+ channel Nav 1.2, cause epilepsy syndromes and predispose children to acute encephalopathy. Here, we report the case of a young male with recurrent acute encephalopathy who carried a novel missense mutation in the SCN2A gene. He was born by normal delivery and developed repetitive apneic episodes at 2 days of age. Diffusion-weighted imaging revealed high-intensity areas in diffuse subcortical white matter, bilateral thalami, and basal nuclei. His symptoms improved gradually without any specific treatment, but he exhibited a motor milestone delay after the episode. At the age of 10 months, he developed acute cerebellopathy associated with a respiratory syncytial viral infection. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy and seemed to have no obvious sequelae after the episode. He then developed severe diffuse encephalopathy associated with gastroenteritis at the age of 14 months. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy but was left with severe neurological sequelae. PCR-based analysis revealed a novel de novo missense mutation, c.4979T>G (p.Leu1660Trp), in the SCN2A gene. This case suggests that SCN2A mutations might predispose children to repetitive encephalopathy with variable clinical and imaging findings.