Christianson syndrome, a genetic nervous system disorder not normally associated with Lennox-Gastaut syndrome (LGS), was unexpectedly found to be the underlying cause of LGS in two children, a case study reported.
The study, “Epilepsy in Christianson syndrome: Two cases of Lennox–Gastaut syndrome and a review of literature,” was published in Epilepsy & Behavior Reports.
LGS is a childhood epilepsy characterized by seizures and impaired mental function. It is accompanied by brain activity with a particular pattern known as slow spike waves, as seen on an electroencephalogram or EEG.
The rare disorder has many different causes, which can be genetic or triggered by brain injuries around birth, problems with blood flow in the brain, or other disorders of the nervous system.
Now, researchers describe the cases of two children diagnosed with LGS in whom a condition called Christianson syndrome (CS) — a disease not previously associated with Lennox-Gastaut — was found to be the underlying cause.
Christianson syndrome is an intellectual disorder linked to the X chromosome and caused by mutations in a gene known as SLC9A6. People with this syndrome are unable to speak, have body control problems and smaller heads, and suffer from muscle spasms and epilepsy.
According to the researchers, “almost all patients with CS develop drug-resistant epilepsy — its most serious complication.”
The first child described in the case report was born uneventfully, with normal birth weight, and developed as expected during infancy. However, at nine months, tonic seizures — sudden stiffness of the body, arms or legs — began occurring several times a day. The boy was referred to the hospital at 11 months for evaluation.
While blood tests and brain images revealed no abnormal findings, the child had a smaller head, mild developmental delay, and EEG patterns that included slow spike waves.
Following treatment with anti-seizure therapies, namely valproate (brand name Convulex, Depakote, among others) and clonazepam (brand name Klonopin, among others), there was a temporary decrease in the number of seizures.
However, the weekly seizures persisted, and when the boy was 3, they became drug-resistant. After that, the child lost his ability to walk, was unable to speak, and had a severe intellectual disability.
By age 7, he was diagnosed with LGS, after developing weekly atonic seizures, known as drop attacks, in addition to tonic seizures. Sleep EEG showed frequent slow spike wave patterns. The seizures decreased at age 14, but weekly tonic seizures during sleep continued, and a brain scan at age 16 revealed mild atrophy, or loss of neurons.
Following the genetic analysis of his entire genome, a mutation in the SLC9A6 gene was identified and Christianson syndrome was confirmed. Further investigation found that his younger sister, who suffered from mild intellectual disability and epilepsy, had the same mutation.
The second child also was born without problems and developed normally until 17 months, after which he began experiencing tonic seizures. He was treated with valproate as an anti-seizure therapy.
By age 3, the number of seizures increased and he was given a second anti-seizure medicine, clobazam, and referred to the hospital for evaluation. An examination found he had a small head, severe intellectual impairment, and was unable to speak. The child also had problems walking and controlling his body, and experienced muscle spasms.
Despite adding more medicines to his anti-seizure regimen — topiramate, lamotrigine, levetiracetam, and carbamazepine — the daily tonic seizures continued and EEG analysis found slow waves patterns. At age 6, the child’s atonic seizures became more frequent and he was diagnosed with LGS. By age 8, only daily tonic seizures occurred during sleep.
As with the first child, the genetic analysis found a different, and previously unreported mutation in the same SLC9A6 gene, also demonstrating Christianson syndrome.
“Our cases illustrate that CS may cause LGS in addition to other developmental and epileptic encephalopathies [brain disease] of the neonatal and infantile period,” the researchers said.
“We suggest that generalized tonic or tonic–clonic seizures and generalized slow spike–wave complexes in interictal [between seizures] EEG be included as potential electroclinical features of epilepsy in CS,” the team concluded.
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