Christianson syndrome: An underestimated cause of electrical status epilepticus in sleep?

Abstract

Objective: Christianson syndrome (CS) is a syndromic form of X-linked severe ID associated to progressive microcephaly, ataxia, autistic behaviour, near absent speech and epilepsy in 90% of cases. The natural history of seizures and EEG abnormalities is insufficiently known. We report two additional families including patients with electrical status epilepticus in sleep (ESES) previously described in only two patients. Methods: We describe two unrelated families with CS caused by SLC9A6 mutations (one frameshift and one partial deletion), each including two boys. One family has been followed for over 20 years, providing insights into the natural course of epilepsy in this syndrome. Results: Onset of epilepsy occurred within the first two years of life in all patients. Seizures were of various types. First EEG recordings showed abnormal fast-background activity with poor antero-posterior organization as reported in the literature. In the two boys with a 20 year follow-up, epilepsy was drug-resistant during childhood, then became less active in early adolescence. EEG background rhythm slowed over time to 4–5Hz after the age of 8 years. One patient from the first family fulfilled the electrical criteria of ESES, between 6 and 8 years of age, while sleep-EEG had not been performed in his brother during this range of age. ESES was diagnosed in the older brother from the second family since the age of 4 years and 10 months. The four boys presented severe ID, autistic features with agitation limiting frequent sleep EEG recordings. Conclusion: Our observations and previous reports, suggest that ESES might be an underestimated feature in CS and may participate to the psychomotor degradation of the patients. Interestingly, SLC9A6 mutations underlie dysfunction in the sodium-hydrogen exchanger NHE6 implicated in plasticity of glutamatergic synapses. Sleep EEGs should be performed in these infants between 4 and 8 years of age.