Genetic testing helps diagnose developmental disorders before birth

Genetic sequencing improved the diagnosis of abnormalities detected in ultrasound scans of developing babies, in new research from Great Ormond Street Hospital (GOSH), the Wellcome Sanger Institute and Birmingham Women’s Hospital.

The study, which was published today in The Lancet, showed that sequencing led to a diagnosis for around 10% of families for whom abnormalities had been detected during a routine ultrasound. Without this genomic information, these abnormalities may not have been fully diagnosed until after birth, if at all.

Overall the team sequenced the DNA of 610 developing babies and 1206 biological parents where abnormalities had been detected in scans. DNA samples were taken after these problems were detected and were analysed by Dr Matt Hurles and colleagues from the Wellcome Trust Sanger Institute. Professor Lyn Chitty, who is Professor of Genetics and Fetal Medicine at GOSH and the UCL Great Ormond Street Institute of Child Health (ICH), coordinated much of the recruitment of pregnant mothers via a network of NHS Fetal Medicine Units across the UK and her team of scientists helped interpret the sequencing data.

Approximately three per cent of pregnancies will have an abnormality, many of which can be detected by a routine prenatal anomaly scan. These can include problems with the baby’s heart, brain, skeleton or in some cases, multiple organs. 

Having identified a problem with the baby’s development using prenatal ultrasound, parents often want to know the likely outcome for their child, however there can be many different possible causes of the abnormality. In this study, the team used a method called whole-exome sequencing in which the parts of the genome that codes for proteins (exons) are sequenced.  In contrast, whole-genome sequencing is the process of reading the genetic code of all genes in the genome.

Professor Chitty, said, “The study shows that exome sequencing improves the diagnosis of genetic conditions in developing babies who have been found to have structural abnormalities during a routine ultrasound. If we can make these results available during pregnancy, it means we can offer better counselling to parents and enable access to appropriate care”. 

Dr Hurles, from the Wellcome Sanger Institute, said: “Genetic testing gets to the root cause of some of the problems seen in ultrasound scans and can give families much clearer answers about a baby’s condition. For example, a structural heart defect seen on an ultrasound scan could be caused by a condition that just affects the heart and may be relatively easily corrected, or it could be linked to something more complicated, such as neurological development, which could impact on the child’s schooling in the future.”

The research supports the use of more detailed genetic testing alongside other tests in order to provide better information to parents about how their child is likely to be affected. "The next step is to work on implementing this approach nationally so more families can benefit, and I am pleased to say that this test will be available as part of the new NHS Genomic Medicine Service later this year.” added Professor Chitty.

These findings come as part of GOSH's established track record in genomics research to help improve care for people affected by rare and complex childhood condition. GOSH played a major role in the recently completed 100,000 Genomes Project, hosting the North Thames Genomic Medicine Centre and sequencing the genomes of over 5500 patients and their relatives. Following this success GOSH will lead the North East and West (NEW) London Genomics Laboratory Hub, one of seven national hubs designed to deliver genomic testing throughout the UK. This pioneering genomics research programme has been supported by a range of funders including the National Institute for Health Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre.

In the study, which also involved collaborators at the Universities of Birmingham, who helped recruit patients, and Cambridge who completed whole-exome sequencing, where the part of the genetic code that codes for the proteins (exomes) are sequenced. Researchers identified definitive diagnoses in 52 of the 610 pregnancies, or 8.5 %. Likely diagnoses were identified in a further 3%. As part of this work new presentations of conditions previously only recognised after birth were also identified.

The team found that genetic diagnoses were considerably more common in fetuses with multi-organ problems, which could lead to some ultrasound findings being prioritised for genetic testing.