Neonatal epileptic encephalopathy misdiagnosed as atypical Rett syndrome

What is it about?

Epileptic encephalopathies are childhood brain disorders characterized by a variety of severe epilepsy syndromes that differ by the age of onset and seizure type. Until recently, the cause of many epileptic encephalopathies was unknown. Whole exome or whole genome sequencing has led to the identification of several causal genes in individuals with epileptic encephalopathy, and the list of genes has now expanded greatly. In this case study, we describe a 33-month-old female child with severe, neonatal onset epileptic encephalopathy.

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Why is it important?

The patient presented in this case report had an early infantile encephalopathy phenotype consistent with a diagnosis of Ohtahara syndrome. An epilepsy gene panel was ordered through a clinical laboratory, and this identified 2 novel MECP2 variants in the proband. One of the variants was evaluated as pathogenic, while the other was of unknown significance. The patient was diagnosed as having severe, atypical RTT. As described in detail below, subsequent testing of both parents and a male sibling suggested that neither of these 2 MECP2 variants was likely to be pathogenic. Family trio-based whole exome sequencing (WES) revealed a novel, rare, de novo mutation in GNAO1 to be the most likely cause of the patient’s condition.

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