CNTN gene: probable cause of Epileptic Encephalopathy Lennox-Gastaut like phenotype.

We report the case of a 17-year-old male patient, with onset of awake atonic-astatic seizures at the age of two years, followed later by seizures in sleep characterized by flexion spasms of upper limbs and atonic absences in wakefulness. At age 6, he presented convulsive status epilepticus with aphasia. Based on the typical electroencephalographic (EEG) pattern of "generalized paroxysmal fast activity", we diagnosed Lennox-Gastaut like Epileptic Encephalopathy. Since 2009, he presented four episodes of Status Epilepticus (SE), two treated with Thiopental and ACTH and two resolved after intravenous Methylprednisone and IgG. During follow-up, brain magnetic resonance showed a progressive cerebral atrophy. Lumbar puncture revealed a moderate damage to the blood-brain barrier. In 2017, Whole Exome Sequencing (WES) was performed that showed a de novo mutation of the CNTN2 gene: c.1810G>A p.Val604Ile. The CNTN2 gene product contactin 2 contributes to the organization of axonal domains at nodes of Ranvier by maintaining voltage-gated potassium channels at the juxtaparanodal region. Contactin 2 plays a role in cortical hyperexcitability and seizure susceptibility. The de novo mutation detected in our patient could implicate the involvement of the CNTN2 gene in a different LGlike epileptic phenotype, with re-evaluation of the therapeutic approach.