How Cedars-Sinai Is Using Whole-Genome Sequencing to Care for Children

Two studies involving investigators at Cedars-Sinai Guerin Children’s and the University of Cambridge, U.K., highlight the growing potential of whole-genome sequencing to transform the diagnosis and treatment of childhood conditions such as cerebral palsy and cancer.

Whole-genome sequencing is an analysis of the roughly 20,000 genes in a person’s DNA. The test, usually performed using a blood or saliva sample, is used to identify genetic variations that may be linked to various diseases.

The first study, published in The Lancet Regional Health–Europe, investigated the use of whole-genome sequencing to identify genetic causes of cerebral palsy in children.

The second study, published in Nature Communications, examined whether rapid whole-genome sequencing—with results available in three to seven days, compared with several weeks for standard testing—could improve the diagnosis and treatment of children with cancer.

“Whole-genome sequencing gives us an opportunity to better understand why a child develops a particular condition and, in some cases, to change how we care for that child,” said David Rowitch, MD, PhD, deputy director of Research at Cedars-Sinai Guerin Children’s, professor of Paediatrics at the University of Cambridge and corresponding author of both studies.

The term for this type of care is “genomic medicine.” The Cedars-Sinai Newsroom spoke with Rowitch to discuss the studies’ implications for children and families and how Cedars-Sinai Guerin Children’s is working to expand access to genomic medicine in Los Angeles and beyond.

Whole-Genome Sequencing and Cerebral Palsy

What is cerebral palsy and how is it diagnosed?

Cerebral palsy is a lifelong condition caused by damage to the developing brain from premature birth, infections or brain injuries. Globally, 18 million people have cerebral palsy, and the condition can affect movement, muscle control, learning and communication skills. It’s typically diagnosed by a pediatrician or neurologist through physical and neurological tests and brain imaging.

Can cerebral palsy have a genetic cause, and how common might that be?

Recent evidence indicates that about 1 in 4 people with cerebral palsy may have an underlying DNA mutation in a specific gene. Genetics has increasingly become an important consideration when evaluating cerebral palsy, and research shows that more than 100 genes are linked to the condition.

Whole-genome sequencing, usually involving the child and both parents, can diagnose genetic conditions and help determine whether a variant was inherited or occurs in the child only.

When should a child with cerebral palsy have whole-genome sequencing?

The appropriate criteria for genetic testing in children with cerebral palsy are not yet well established. More guidelines are needed to help decide when to test. If a genetic cause is suspected, such as no known risk factors, testing children early may help guide treatment and care.

How does finding an underlying genetic cause change cerebral palsy treatment?

A genetic diagnosis can lead to precision medicine treatments and help physicians identify other health risks that should be monitored. For example, if we found that cerebral palsy is part of a genetic syndrome that has a cardiac component, we would refer that patient for cardiology consultation and assessment. In our study, we changed care plans for about 63% of children who received a genetic diagnosis.

How is whole-genome sequencing improving cerebral palsy care at Guerin Children’s?

Identifying the specific genes involved in the disease creates opportunities for new research that may lead to new treatments, such as gene therapy.

At Cedars-Sinai Guerin Children’s, we are researching a gene called CTNNB1, which is commonly found in patients with cerebral palsy. This research aims to help us understand what goes wrong in the nervous systems of children with this gene mutation. We recently launched a whole-genome sequencing protocol for use in neonatal and pediatric intensive care units to expand our research and its benefits to patients.

Rapid Whole-Genome Sequencing and Childhood Cancer

How can rapid whole-genome sequencing change a child’s cancer care?

Previous studies from the University of Cambridge showed that whole-genome sequencing was more effective than standard genetic tests for diagnosing childhood cancer, but results took three to six weeks.

Faster results can help clinicians provide a more precise diagnosis, make treatment decisions earlier, avoid unnecessary interventions or treatments, and adjust chemotherapy dose. In our study of 54 children with cancer, we concluded that about 50% of the cases benefited from having a more rapid return of results. For some children, we adjusted their chemotherapy dose to fit their metabolism; for others, we switched medications. In one dramatic case, we withheld treatment.

What are the next steps for bringing rapid whole-genome sequencing into routine pediatric cancer care?

Our study, although it was small and involved a limited patient population, showed clear benefits. National adoption of rapid whole-genome sequencing is being tested in the U.K. In the U.S., this will require institutions to champion this diagnostic approach and increase access and capacity.

At Cedars-Sinai Guerin Children’s, an important next step is to explore how these capabilities can be extended more broadly to pediatric oncology and other specialties where genomic information can make a difference. The goal is not simply to provide a diagnosis, but to help clinicians choose the right care for each child.

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