Suls et al. (2009) identified heterozygous mutations in the SLC2A1 gene in 4 (12%) of 34 patients with early-onset absence epilepsy before age 4 years. CSF glucose levels were not available from any of the patients. One of ... Suls et al. (2009) identified heterozygous mutations in the SLC2A1 gene in 4 (12%) of 34 patients with early-onset absence epilepsy before age 4 years. CSF glucose levels were not available from any of the patients. One of the patients had no additional abnormalities and normal development. However, clinical review of these patients after diagnosis showed that 3 had mild to moderate mental retardation, 2 had mild ataxia, and 1 had myoclonus and exercise-induced paroxysmal dyskinesia. None had microcephaly. Two patients inherited missense mutations from parents with later-onset absence epilepsy. Mullen et al. (2010) reported significant intrafamilial clinical variability in 2 unrelated families with SLC2A1 mutations: 1 with 9 mutation carriers spanning 2 generations and the other with 6 mutation carriers spanning 2 generations. Of 15 patients with SLC2A1 mutations, 12 had epilepsy, most commonly absence epilepsy, with onset between ages 3 and 34 years. Eight patients had idiopathic generalized epilepsies with absence seizures, 2 had myoclonic-astatic epilepsy, and 2 had focal epilepsy. Seven patients had subtle paroxysmal exertional dyskinesia as the only manifestation, and 2 mutation carriers were unaffected. Only 3 of 15 patients had mild intellectual disabilities. Mullen et al. (2010) emphasized the phenotypic overlap with common forms of idiopathic generalized epilepsy. Striano et al. (2012) reported a large Italian family in which 9 individuals spanning 3 generations had various forms of epilepsy. The age at seizure onset ranged from early childhood to 23 years. All had generalized seizures, mainly typical absence seizures, and EEG showed regular, symmetric discharges of 3 to 3.5 Hz spike wave complexes. Seizures typically remitted 2 to 5 years after onset, although 1 patient later developed juvenile myoclonic epilepsy. Most showed a favorable response to pharmacologic treatment. None of the patients had other neurologic manifestations, including movement disorders.
Suls et al. (2009) reported a 28-year-old woman with early-onset absence epilepsy at age 3 years and generalized tonic-clonic seizures at age 7. She had normal intelligence and remission of seizures with medication at age 7. CSF glucose ... Suls et al. (2009) reported a 28-year-old woman with early-onset absence epilepsy at age 3 years and generalized tonic-clonic seizures at age 7. She had normal intelligence and remission of seizures with medication at age 7. CSF glucose levels were not available. Genetic analysis identified a heterozygous mutation in the SLC2A1 gene (138140.0020). The findings indicated that SLC2A1 mutations may contribute to relatively mild forms of epilepsy. In 1 of 95 families with EIG, Striano et al. (2012) identified a heterozygous missense mutation in the SLC2A1 gene (R232C; 138140.0019). All 8 living patients with seizures in this family carried the mutation, which was also found in 4 healthy adult family members, yielding a penetrance of 67%. In vitro functional studies showed that the mutant protein was expressed at the cell surface but had mildly decreased glucose uptake (70%) compared to wildtype. The findings suggested that GLUT1 deficiency is a rare cause of typical EIG, and also expanded the phenotypic spectrum associated with mutations in the SLC2A1 gene.