Paediatric neurologists have witnessed a transformational improvement in our ability to identify the aetiology of neurological disorders affecting children. The advent of modern neuroimaging allowed us to identify abnormalities, in particular those due to acquired brain injuries. Improvements in our understanding of metabolism and greater resolution on the human genome with microarray, then gene sequencing, allowed us to identify the underlying genomic aetiology in many cases. Despite these advances, the majority of families are often left unclear as to the causation of the neurological disorder affecting their child.

Two recent advances are likely to produce a further step up. First, trio whole genome sequencing (WGS) when combined with microarray has been shown to identify the underlying aetiology in children affected with probable genomic disorders in over 50% of selected cases.1 In the great majority, the child’s sequence will need to be compared to parental samples before pathogenicity is defined.2 If parental samples are taken subsequently, this unnecessarily delays diagnosis and introduction of precise/disease-modifying therapies. Although ‘curative’ treatments are rare, the majority of families will benefit from improved management through combinations of: (1) disease modification (e.g. enzyme replacement for CLN2); (2) more precise therapies (e.g. stiripentol for SCN1A); (3) rational treatment regimes (e.g. carbamazepine for KCNQ2 and not for SCN1A); and (4) evidence-based counselling (e.g. the low likelihood of seizure remission in CDKL5, with consequent emphasis on multidisciplinary support rather than a continuing diagnostic odyssey).1, 2 Consent for samples and sequencing on parents can be taken in parallel with the child, but only by appropriately trained and confident professionals.

Second, our ability to identify abnormalities within the fetus through antenatal magnetic resonance imaging and trio WGS.3, 4 However, as in all investigations, interpretation risks false positive/negatives and grey areas. These services will need to develop multidisciplinary teams working equitably across diverse communities to provide expert diagnostic services. More importantly, accurate prognostication will need to be done and imparted to prospective parents in a way that they can understand and minimizes distress.

Developing the ability to undertake these investigations quickly, accurately, compassionately, and equitably across the UK is likely to be challenging for all healthcare centres. The British Paediatric Neurology Association (BPNA) Annual Conference 2022 will highlight many issues, with particular reference to fetal neurology and rapid trio WGS. The BPNA is committed to helping regional services to develop these services. One size may not fit all, but there are likely to be simple lessons that can be shared. Regional centres will need to think carefully on how these complex services are developed, whilst the National Health Service in the UK reconfigures following the pandemic. We will only succeed if we lobby at district, regional, and national levels, engaging the power of the children’s voices through the wonderful families who care for them.