Neurofibromatosis type I (NF-1) is a tumour disorder caused by the mutation of a gene on chromosome 17 that is responsible for control of cell division. It causes tumours along the nervous system that can grow anywhere in the body. Routine screening investigations are not recommended for the detection of the majority of complications associated with the condition. Baseline brain and spine MRI, and routine imaging of the chest and abdomen to identify asymptomatic tumours, do not influence management and should not be undertaken.
A heterogeneous genetic disorder is one where the same disease or condition can be caused, or contributed to, by a number of different genes. The traditional strategy for genetic testing involves sequential sequencing of individual genes, selected according to the patient’s clinical presentation and family history. By contrast, next generation sequencing (NGS) involves the sequencing of millions of small fragments of DNA at the same time. Reductions in the cost of NGS now make it a more attractive solution for clinical diagnostic testing to identify the disease-causing mutation(s) in patients with genetically heterogeneous disorders than traditional sequential testing. In particular, the targeted NGS approach which restricts analysis to genes known to be implicated in a particular phenotype has been also successfully applied to heterogeneous disorders such as inherited peripheral neuropathy (IP).
While genetic testing can help indicate susceptibility to particular genetic conditions, there are some conditions where the presence of particular alleles is neither necessary nor sufficient to cause the condition or where the alleles have a higher prevalence in the general population than the condition itself. This is the case for instance with apolipoprotein E as a genetic marker for Alzheimer’s disease and methylenetetrahydrofolate as a marker for venous thromboembolism.
With a rare recessive disorder, although the individual with the family history will have an increased risk of being a carrier, their unrelated partner will have a low general population risk. Therefore, their a priori combined risk of having a child with this rare recessive condition will generally be less than 1%. If the gene has no known common disease causative mutations then testing the unrelated partner for carrier status has low sensitivity and specificity.
Like other screening or diagnostic tests, genetic tests do not have inherent utility. It is the adoption of therapeutic or preventive interventions that influences health outcomes. If clinical diagnostic criteria already exist for the condition in question and there are no reproductive or other predictive testing implications as a result of definitively identifying a genetic cause for the condition, then this renders genetic testing unnecessary.