Paediatric genomics: diagnosing rare disease in children

Caroline F. Wright, David R. FitzPatrick & Helen V. Firth, Nature Reviews Genetics, Published online:05 February 2018, doi:10.1038/nrg.2017.116

The majority of rare diseases affect children, most of whom have an underlying genetic cause for their condition. However, making a molecular diagnosis with current technologies and knowledge is often still a challenge. Paediatric genomics is an immature but rapidly evolving field that tackles this issue by incorporating next-generation sequencing technologies, especially whole-exome sequencing and whole-genome sequencing, into research and clinical workflows. This complex multidisciplinary approach, coupled with the increasing availability of population genetic variation data, has already resulted in an increased discovery rate of causative genes and in improved diagnosis of rare paediatric disease. Importantly, for affected families, a better understanding of the genetic basis of rare disease translates to more accurate prognosis, management, surveillance and genetic advice; stimulates research into new therapies; andenables provision of better support.

Ethical, legal and social implications of paediatric genomics:
Paediatric genomics has many of the same ethical, legal and social issues that clinical genetics has been dealing with for decades, such as reproductive autonomy, informed consent for research, misattributed parentage and implications for family members. Issues which are more complicated for paediatric testing: the reduced capacity of the child to consent to testing and/or research means that parents and clinicians have an increased role in deciding what may be in the best interests of the child. Most of the novel ethical issues in the era of genomics relate to the storage, interpretation and access of data.


Data storage: it is not clear who should have access to that data and when they should be allowed access to it. Should access be limited to clinicians involved in the direct care of the family or opened to researchers in industry and/or academia?
Confidentiality versus data access: Parents are often asked to make decisions about their child’s data that may have irreversible repercussions. Should these decisions be revisited when the child approaches and passes the age of majority?
Duty of care: For clinicians, the issue of data access is linked to the question of whether their duty of care is limited to finding a diagnosis for the child’s immediate problems or whether it extends beyond the scope of the initial investigation. The duty of care could also extend to looking for incidental predispositions to adult-onset conditions or to adverse drug reactions either in the child or their parents. In general, investigating children for adult-onset conditions for which there is no early treatment is not recommended.

Paediatric genomics: diagnosing rare disease in children