EIEE11 is an autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities (Ogiwara et al., 2009).
For a general phenotypic description and a discussion of ... EIEE11 is an autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities (Ogiwara et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Kamiya et al. (2004) reported a 29-year-old Japanese woman with delayed onset of early infantile epileptic encephalopathy-11. She had onset of seizures at age 1 year, 7 months, and thereafter became hyperkinetic and autistic. The EEG was reported ... Kamiya et al. (2004) reported a 29-year-old Japanese woman with delayed onset of early infantile epileptic encephalopathy-11. She had onset of seizures at age 1 year, 7 months, and thereafter became hyperkinetic and autistic. The EEG was reported to show only slow waves initially, but after 3 years, there was clear focal onset and spike activity appeared and increased. Convulsive and atonic seizures continued throughout childhood and were difficult to treat. She had severe intellectual and psychomotor retardation but no paralysis. Brain MRI showed moderate diffuse brain atrophy. Ogiwara et al. (2009) reported 2 unrelated patients with early infantile epileptic encephalopathy. The first patient had onset of infantile spasms at age 11 months, which evolved to frequent occurrence of refractory tonic-clonic seizures at age 2 to 3 years. He also showed marked developmental delay and severe intellectual disability in infancy and childhood. Febrile seizures occurred after age 10 years. After an episode of status epilepticus at age 17 years, he became quadriplegic and speechless. EEG showed background activity lacking alpha waves but containing abundant slow waves and right hemisphere dominant diffuse sharp waves or polyspikes; ictal EEG showed diffuse recruiting fast spike activity preceded by diffuse flattening. MRI showed mild cerebral atrophy with wider left lateral ventricle. The second patient developed tonic or tonic-clonic seizures from age 1 month. She also had early infantile status epilepticus with a highly suppressed EEG with ictal burst activities, hyponatremia, and megalencephaly. The seizures were responsive to lidocaine treatment. She died at age 7 years and 8 months from unknown causes. The reports of these patients significantly expanded the phenotype resulting from SCN2A mutations, and indicated that SCN2A is a candidate gene underlying intractable childhood epilepsies. In vitro functional expression studies showed that both E1211K and I1473M altered the channel properties of SCN2A to a greater extent than the BFIS3 mutations, suggesting a molecular mechanism for the more severe epileptic phenotypes. - Clinical Variability Liao et al. (2010) reported an 11-year-old boy with neonatal onset of seizures followed by unusually long persistence of seizures as well as residual neurologic signs. The phenotype was considered to be more severe than that of BFIS3. He presented from the first day of life with hypomotor seizures followed by tonic-clonic movements on alternating sides. Hypomotor, focal, and bilateral motor seizures continued weekly to monthly until 1.3 years. Beginning at this time, he developed episodes with poor balance, ataxia, slurred speech, intermittent myoclonic jerks, and severe distress with headache, back pain, hypermotor activity, hyperventilation, and retching or vomiting. Mild motor dyspraxia, but no ataxia, was present between the episodes. After numerous medications that were ineffective, he became seizure-free on acetazolamide. Neuropsychologic testing showed normal intelligence, but specific problems in visual processing, fine motor function, and tactile sensation. MRI showed mild cerebellar atrophy at age 5 years.
In a 29-year-old Japanese woman with delayed onset of early infantile epileptic encephalopathy-11, Kamiya et al. (2004) identified a de novo heterozygous truncating mutation in the SCN2A gene (R102X; 182390.0008). Electrophysiologic studies in HEK293 cells showed that the ... In a 29-year-old Japanese woman with delayed onset of early infantile epileptic encephalopathy-11, Kamiya et al. (2004) identified a de novo heterozygous truncating mutation in the SCN2A gene (R102X; 182390.0008). Electrophysiologic studies in HEK293 cells showed that the R102X mutant protein was nonfunctional when expressed in isolation, and shifted the voltage dependence of inactivation of wildtype channels in the hyperpolarizing direction, consistent with a dominant-negative effect. In 2 unrelated patients with early infantile epileptic encephalopathy-11, Ogiwara et al. (2009) identified 2 different de novo heterozygous missense mutations in the SCN2A gene (E1211K; 182390.0009 and I1473M; 182390.0010, respectively). In an 11-year-old boy with early-onset seizures and persistent neurologic impairment, Liao et al. (2010) identified a de novo heterozygous mutation in the SCN2A gene (A263V; 182390.0011).