Can genome sequencing find a diagnosis for undiagnosed genetic disorders in newborns?
Genome sequencing is a powerful tool for identifying the genetic causes of rare disorders in newborns who have not yet received a diagnosis. Research shows that testing can provide a molecular diagnosis in roughly one out of five cases, though the exact rate varies based on factors like the number of symptoms and the specific testing method used. This approach helps doctors understand conditions that were previously difficult to classify.
What the research says
A large study of over 3,000 newborn and pediatric cases found that the overall diagnostic yield from exome and genome sequencing was 19.0%. This means that in about 19% of cases, the test identified a genetic cause for the child's condition. The study noted that having multiple clinical indications, or several symptoms, was associated with a higher chance of finding a diagnosis 3.
Another study of 814 patients with suspected genetic conditions found an overall molecular diagnosis rate of 26%. When parents and child were tested together (trio-CES), the diagnosis rate was 31%, compared to 22% when only the child was tested. This suggests that testing the family together can improve the ability to find a diagnosis 5.
Research also shows that sequencing can identify new genes responsible for developmental disorders. In one large study of 1,133 children with severe, undiagnosed developmental issues, using exome sequencing and chromosomal analysis discovered 12 new genes. This expanded the list of known causes and increased the proportion of children who could be diagnosed from 28% to 31% 6.
Whole genome sequencing is also effective for specific types of disorders, such as neurological repeat expansion disorders. A study in the UK assessed its accuracy for detecting these conditions and found it useful for patients with atypical presentations or no family history, which are often missed by standard genetic tests 7.
What to ask your doctor
- What is the likelihood of finding a diagnosis for my child's specific symptoms using genome sequencing?
- How does testing the parents alongside the child (trio-CES) affect the chance of finding a diagnosis?
- Are there specific types of disorders, like repeat expansion disorders, that require whole genome sequencing instead of exome sequencing?
- What new genes or conditions might be discovered that could explain my child's symptoms?
- How will a genetic diagnosis change the care plan or treatment options for my newborn?
This question is drawn from common patient questions about Genetics & Precision Medicine and answered using cited medical research. We do not provide individualized advice.