173 - Pathophysiology of Genetic Neonatal Disease

Abstract

Genetic diseases are a leading cause of neonatal morbidity and mortality. Estimates of the incidence of genetic disease in neonates admitted to intensive care units have historically been based on targeted genetic testing of cohorts selected to have a high pre-test probability, such as those with multiple congenital anomalies. However, the neonatal presentation of many thousands of genetic diseases overlaps with common, typically non-genetic conditions such as sepsis, hypoxic ischaemic encephalopathy and in-utero infections. It is now possible to explore the potential for many non-specific, life-threatening neonatal presentations to have a monogenic or genomic aetiology. This has become made possible with the availability of clinical grade genome-wide sequencing technologies (whole exome sequencing or whole genome sequencing). Healthcare policy makers worldwide are beginning to make decisions about the availability of, and eligibility for, neonatal genomic tests. It has never been more important for healthcare professionals who care for critically ill neonates to become familiar with the scientific rationale for use of these evolving genomic technologies, as well as interpreting genetic sequencing results, topics we will explore in this chapter.