Fifteen-minute consultation: The efficient investigation of infantile and childhood epileptic encephalopathies in the era of modern genomics.

The investigation of children presenting with infantile and childhood epileptic encephalopathies (ICEE) is challenging due to diverse aetiologies, overlapping phenotypes and the relatively low diagnostic yield of MRI, electroencephalography (EEG) and biochemical investigations. Careful history and thorough examination remain essential as these may identify an acquired cause or indicate more targeted investigation for a genetic disorder. Whole exome sequencing (WES) with analysis of a panel of candidate epilepsy genes has increased the diagnostic yield. Whole genome sequencing (WGS), particularly as a trio with both parents' DNA, is likely to supersede WES. Modern genomic investigation impacts on the timing and necessity of other testing. We propose a structured approach for children presenting with ICEE where there is diagnostic uncertainty, emphasising the importance of WGS or, if unavailable, WES early in the investigative process. We note the importance of expert review of all investigations, including radiology, neurophysiology and biochemistry, to confirm the technique used was appropriate as well as the results. It is essential to counsel families on the risks associated with the procedures, the yield of the procedures, findings that are difficult to interpret and implication of 'negative' results. Where children remain without a diagnosis despite comprehensive investigation, we note the importance of ongoing multidisciplinary care.

Fifteen-minute consultation: Efficient investigation of the child with early developmental impairment in the era of genomic sequencing.

The investigation of children with early developmental impairment (EDI) is challenging in terms of selecting investigations and supporting families through the diagnostic pathway. Modern genomic sequencing has the potential to greatly improve yield of investigation, but produces challenges in terms of timing and explaining its strengths/weaknesses to families. We present an evidence-based and practical guideline to help the paediatrician through all stages of investigation. We emphasise the importance of a really good history and examination, allowing targeted investigation for specific disorders and outline an approach for isolated EDI when this is not possible. This prioritises genetic investigation- after appropriate counselling to families, and balances the very low yield of biochemical/radiological investigations in isolated EDI, with the need to detect extremely rare, but potentially treatable disorders. Collaboration with both families and regional specialists to ensure appropriate testing is likely to reduce parental and clinician anxiety.