Epileptic Encephalopathy, Early Infantile, 40
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-40 (EIEE40) is caused by homozygous mutation in the GUF1 gene (617064) on chromosome 4p12. One such family has been reported.
For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Clinical FeaturesAlfaiz et al. (2016) reported 3 sibs, born of consanguineous Algerian parents, with onset of refractory seizures associated with hypsarrhythmia between 4 and 6 months of age. Onset of seizures was associated with psychomotor arrest and poor neurologic outcome, including poor or absent eye contact, hypotonia, spasticity, spastic tetraparesis and choreoathetosis (in 1 patient), dystonic fits, no babbling, and an inability to handle small objects. Brain imaging of 1 patient was normal at first, but later showed diffuse cortical atrophy. Laboratory studies showed normal levels of lactate and pyruvate in cerebrospinal fluid.
InheritanceThe transmission pattern of EIEE40 in the family reported by Alfaiz et al. (2016) was consistent with autosomal recessive inheritance.
Molecular GeneticsIn 3 sibs, born of consanguineous Algerian parents, with EIEE40, Alfaiz et al. (2016) identified a homozygous missense mutation in the GUF1 gene (A609S; 617064.0001). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Yeast complementation studies showed that the mutant protein retained some residual activity, but was less proficient than wildtype under suboptimal conditions, such as in the presence of an oxidizing compound that interferes with faithful protein synthesis.