The spectrum of epilepsy in developmental and epileptic encephalopathy (DEE) associated with ST3GAL3 mutations may include early onset infantile seizures that evolve into Lennox-Gastaut syndrome (LGS), according to a new study published in the journal Epilepsia Open.
The study authors also said that mixed-type seizures responding well to antiseizure medications may also occur later in childhood.
Read more about the genetics of LGS
These findings are based on the case of 2 brothers and a literature review.
The 2 brothers had developmental delays, motor and language impairment, hypotonia, and seizures that started when they were between 2.5 and 5 years old. The younger brother also had tremor. Both boys were free from seizures for long periods of time with carbamazepine treatment. Genetic testing showed 2 novel pathogenic variants in the ST3GAL3 gene inherited in trans. Magnetic resonance imaging revealed T2 hyperintensities and restricted diffusion in the brainstem as well as the middle cerebellar peduncle in the older boy.
The literature review identified 24 cases of congenital disorder of glycosylation related to ST3GAL3 mutations. Of these, 12 contained information about seizures. The majority of those (67%) were diagnosed with epilepsy.
The median age of the reported patients at the time of onset of seizures was 5.5 months. The most common type of seizure was epileptic spasms reported in 67% of the cases.
A total of 4 children were diagnosed with infantile epileptic spasms syndrome and LGS.
Antiseizure medications were inefficient in most children (75%). The authors said that more research is needed to identify which antiseizure medications could be most effective in ST3GAL3-related DEE.
LGS is a rare and severe type of childhood epilepsy characterized by variable seizure types such as tonic, atypical absence, intellectual disability, generalized tonic-clonic, myoclonic seizure, atonic, and distinctive electroencephalogram abnormalities.
Whitney R, Jain P, RamachandranNair R, et al. The epilepsy phenotype of ST3GAL3-related developmental and epileptic encephalopathy. Epilepsia Open. Published online April 17, 2023. doi:10.1002/epi4.12747