Phenotype expansion and neurological manifestations of neurobehavioural disease caused by a variant in RFX7.

The RFX7 gene is one of eight genes within the regulatory factor X family. RFX7 is highly expressed in the brain and plays an important role in cell maturation and differentiation. It has only recently been implicated in disease in humans. Reports from 15 individuals have described RFX-associated phenotype as a neurobehavioural disease, manifesting primarily with global developmental delay and intellectual disability. Autism spectrum disorder and attention deficit hyperactivity disorder have also been described in some children. Here we report a case of a 19-month-old with a de novo missense variant in RFX7 resulting in severe global developmental delay including significant speech delay, microcephaly, dyskinetic movements, and failure to thrive. This is the first association between variants in RFX7 and failure to thrive, expanding the phenotype of this newly described gene. In this report we will also show RFX7 associated progressive central nervous system involvement through serial brain imaging.

Management of seizures in neonates with neonatal encephalopathy treated with hypothermia.

Neonatal encephalopathy (NE) is the most common etiology of acute neonatal seizures - about half of neonates treated with therapeutic hypothermia for NE have EEG-confirmed seizures. These seizures are best identified with continuous EEG monitoring, as clinical diagnosis leads to under-diagnosis of subclinical seizures and over-treatment of events that are not seizures. High seizure burden, especially status epilepticus, is thought to augment brain injury. Treatment, therefore, is aimed at minimizing seizure burden. Phenobarbital remains the mainstay of treatment, as it is more effective than levetiracetam and easier to administer than fosphenytoin. Emerging evidence suggests that, for many neonates, it is safe to discontinue the phenobarbital after acute seizures resolve and prior to hospital discharge.