Tohyama et al. (2008) reported a Japanese infant girl who developed tonic seizures, tremulous arm movements, and oral automatisms at 45 days of age. Her dizygotic twin was unaffected; the pregnancy resulted from in vivo fertilization. The proband ... Tohyama et al. (2008) reported a Japanese infant girl who developed tonic seizures, tremulous arm movements, and oral automatisms at 45 days of age. Her dizygotic twin was unaffected; the pregnancy resulted from in vivo fertilization. The proband continued to have seizures with increased frequency, spastic quadriplegia, and poor visual attention. EEG showed a suppression-burst pattern and hypsarrhythmia, consistent with EIEE. She had severely delayed psychomotor development with no language. Brain MRI showed diffuse hypomyelination, cortical atrophy, and a thin corpus callosum. Saitsu et al. (2008) reported 4 Japanese patients with EIEE. All had neonatal or infantile onset of tonic-clonic or tonic seizures, suppression-burst pattern on EEG, profound mental retardation, and MRI evidence of hypomyelination. Other features included hypsarrhythmia and spastic di- or quadriplegia. Major structural brain abnormalities were not observed. Hamdan et al. (2009) reported 2 unrelated French Canadian patients with EIEE4. One patient was a 27-year-old woman who first developed partial complex seizures at age 6 weeks. The second patient was a 15-year-old girl who first developed partial complex seizures at 2 years, 9 months of age. Both patients had severe mental retardation, hypotonia, and tremor. Brain scan in both patients was normal. Hamdan et al. (2009) noted that the phenotypes of both patients were slightly different than that reported by Saitsu et al. (2008), with later onset of seizures and some response to antiepileptic medication. In addition, hypsarrhythmia was never observed. Deprez et al. (2010) identified heterozygous truncating mutations in the STXBP1 gene in 6 (5.7%) of 106 patients with various types of early-onset epileptic encephalopathies. Variable seizures first occurred between 3 days and 4.5 months of life, and all patients subsequently had severe to profound mental retardation. Three patients developed hypsarrhythmia by 5 months of age, consistent with a clinical diagnosis of West syndrome. Four patients showed an initial favorable response to vigabatrin and became seizure-free later in childhood even without medication, but 2 had continued seizures despite treatment with antiepileptic medications. None of the patients had a burst-suppression pattern on EEG, as had been observed in the patients reported by Saitsu et al. (2008). Three patients were wheelchair-bound due to hypotonia or dyskinesias. Five patients had proven de novo mutations; parental DNA from the sixth patient was not available. Deprez et al. (2010) emphasized the phenotypic variability in the severity of the epilepsy, but noted that all patients had mental retardation, which suggested that neurodegeneration is an intrinsic property of the disorder.
In a Japanese girl with early infantile epileptic encephalopathy (Tohyama et al., 2008), Saitsu et al. (2008) identified a de novo heterozygous microdeletion at chromosome 9q33.3-q34.11 including the STXBP1 gene. Screening of this gene in 13 additional unrelated ... In a Japanese girl with early infantile epileptic encephalopathy (Tohyama et al., 2008), Saitsu et al. (2008) identified a de novo heterozygous microdeletion at chromosome 9q33.3-q34.11 including the STXBP1 gene. Screening of this gene in 13 additional unrelated patients with a similar phenotype identified 4 different heterozygous mutations in the STXBP1 gene (602926.0001-602926.0004) in 4 patients. In 3 of the patients the mutation was shown to be de novo. Saitsu et al. (2008) concluded that haploinsufficiency of STXBP1 results in impaired synaptic vesicle release and the phenotype of EIEE. In 2 unrelated French Canadian patients with severe mental retardation and epilepsy, Hamdan et al. (2009) identified respective de novo heterozygous truncating mutations in the STXBP1 gene (602926.0005 and 602926.0006). The patients were ascertained from a larger group of 95 patients with idiopathic mental retardation.