Early infantile epileptic encephalopathy-17 is a severe neurologic disorder characterized by onset of intractable seizures in the first weeks or months of life and usually associated with EEG abnormalities. Affected infants have very poor psychomotor development and may ... Early infantile epileptic encephalopathy-17 is a severe neurologic disorder characterized by onset of intractable seizures in the first weeks or months of life and usually associated with EEG abnormalities. Affected infants have very poor psychomotor development and may have brain abnormalities, such as cerebral atrophy or thin corpus callosum. Some patients may show involuntary movements (summary by Nakamura et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Nakamura et al. (2013) reported 4 unrelated girls with early infantile epileptic encephalopathy. Three patients had onset of intractable tonic seizures in the first weeks of life associated with suppression-burst pattern on EEG; the fourth patient presented with ... Nakamura et al. (2013) reported 4 unrelated girls with early infantile epileptic encephalopathy. Three patients had onset of intractable tonic seizures in the first weeks of life associated with suppression-burst pattern on EEG; the fourth patient presented with opisthotonic posturing and developmental delay at age 7 months. All had severely delayed psychomotor development, with lack of sitting and no speech; only 1 patient had head control. One child died at age 11 months. EEG studies were consistently abnormal, including hypsarrhythmia and multifocal sharp waves. One patient showed dystonia and another had severe chorea and athetosis. Brain MRI was abnormal in 3 patients, showing cerebral atrophy, delayed myelination, and/or thin corpus callosum.
In 4 unrelated girls with early infantile epileptic encephalopathy-17, Nakamura et al. (2013) identified 4 different de novo heterozygous mutations in the GNAO1 gene (139311.0001-139311.0004). One of the patients was somatic mosaic for the mutation. The mutations in ... In 4 unrelated girls with early infantile epileptic encephalopathy-17, Nakamura et al. (2013) identified 4 different de novo heterozygous mutations in the GNAO1 gene (139311.0001-139311.0004). One of the patients was somatic mosaic for the mutation. The mutations in the first 2 patients were found by whole-exome sequencing, and the mutations in the second 2 patients were found by direct sequencing of the GNAO1 gene in 367 individuals with epileptic encephalopathy. In vitro functional expression studies showed that 3 of the mutations caused impaired protein localization to the plasma membrane, and electrophysiologic analysis showed that 3 of the mutations caused decreased GNAO1-mediated inhibition of calcium currents by norepinephrine compared to wildtype. The findings suggested that aberrant GNAO1 signaling can cause multiple neurodevelopmental phenotypes, including epileptic encephalopathy and involuntary movements.