#616645
Table of Contents
A number sign (#) is used with this entry because of evidence that developmental and epileptic encephalopathy-34 (DEE34) is caused by homozygous or compound heterozygous mutation in the SLC12A5 gene (606726) on chromosome 20q12.
Developmental and epileptic encephalopathy-34 (DEE34) is an autosomal recessive severe neurologic disorder characterized by onset of refractory migrating focal seizures in the first year of life after normal early development. Affected children show developmental regression and are severely impaired globally (summary by Stodberg et al., 2015).
For a discussion of genetic heterogeneity of DEE, see 308350.
Stodberg et al. (2015) reported 4 children from 2 unrelated families with DEE presenting as epilepsy of infancy with migrating focal seizures (EIMFS). Between 6 weeks and 4 months of age, the patients presented with focal seizures manifest as eye deviation, unresponsiveness, apnea, hemiclonic twitching, and tonic and atonic seizures. There was global developmental regression after onset of seizures, and the seizures were pharmacoresistant. EEG showed variable foci of epileptic activity as well as interictal diffuse slowing and multifocal spikes; at least 1 patient had status epilepticus with migrating foci. Brain imaging showed global cerebral atrophy and delayed myelin maturation of the white matter. Some patients showed hypotonia and decreased head circumference. All patients had significantly delayed psychomotor development.
The transmission pattern of DEE34 in the families reported by Stodberg et al. (2015) was consistent with autosomal recessive inheritance.
In 4 children from 2 unrelated families with DEE34, Stodberg et al. (2015) identified compound heterozygous or homozygous missense mutations in the SLC12A5 gene (606726.0001-606726.0003). The mutations were found by exome sequencing and segregated with the disorder in the families. In vitro functional expression studies showed that the mutations caused decreased membrane expression, impaired posttranslational modification, and a loss of transporter function, resulting in impaired normal synaptic inhibition and promotion of neuronal excitability.
Stodberg, T., McTague, A., Ruiz, A. J., Hirata, H., Zhen, J., Long, P., Farabella, I., Meyer, E., Kawahara, A., Vassallo, G., Stivaros, S. M., Bjursell, M. K. Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures. Nature Commun. 6: 8038, 2015. Note: Electronic Article. [PubMed: 26333769, images, related citations] [Full Text]
Alternative titles; symbols
ORPHA: 293181; DO: 0080460;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 20q13.12 | Developmental and epileptic encephalopathy 34 | 616645 | Autosomal recessive | 3 | SLC12A5 | 606726 |
A number sign (#) is used with this entry because of evidence that developmental and epileptic encephalopathy-34 (DEE34) is caused by homozygous or compound heterozygous mutation in the SLC12A5 gene (606726) on chromosome 20q12.
Developmental and epileptic encephalopathy-34 (DEE34) is an autosomal recessive severe neurologic disorder characterized by onset of refractory migrating focal seizures in the first year of life after normal early development. Affected children show developmental regression and are severely impaired globally (summary by Stodberg et al., 2015).
For a discussion of genetic heterogeneity of DEE, see 308350.
Stodberg et al. (2015) reported 4 children from 2 unrelated families with DEE presenting as epilepsy of infancy with migrating focal seizures (EIMFS). Between 6 weeks and 4 months of age, the patients presented with focal seizures manifest as eye deviation, unresponsiveness, apnea, hemiclonic twitching, and tonic and atonic seizures. There was global developmental regression after onset of seizures, and the seizures were pharmacoresistant. EEG showed variable foci of epileptic activity as well as interictal diffuse slowing and multifocal spikes; at least 1 patient had status epilepticus with migrating foci. Brain imaging showed global cerebral atrophy and delayed myelin maturation of the white matter. Some patients showed hypotonia and decreased head circumference. All patients had significantly delayed psychomotor development.
The transmission pattern of DEE34 in the families reported by Stodberg et al. (2015) was consistent with autosomal recessive inheritance.
In 4 children from 2 unrelated families with DEE34, Stodberg et al. (2015) identified compound heterozygous or homozygous missense mutations in the SLC12A5 gene (606726.0001-606726.0003). The mutations were found by exome sequencing and segregated with the disorder in the families. In vitro functional expression studies showed that the mutations caused decreased membrane expression, impaired posttranslational modification, and a loss of transporter function, resulting in impaired normal synaptic inhibition and promotion of neuronal excitability.
Stodberg, T., McTague, A., Ruiz, A. J., Hirata, H., Zhen, J., Long, P., Farabella, I., Meyer, E., Kawahara, A., Vassallo, G., Stivaros, S. M., Bjursell, M. K. Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures. Nature Commun. 6: 8038, 2015. Note: Electronic Article. [PubMed: 26333769] [Full Text: https://doi.org/10.1038/ncomms9038]
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