Reviewed by Bret Stetka, MD

Advances in human genetics have no doubt ushered in a new understanding of disease.

Decoding the molecular interactions between DNA, RNA, and proteins – the biological dance that enables life – has allowed doctors and scientists to better grasp what causes countless medical conditions, and, more importantly, create an opportunity to better diagnose and more effectively manage these maladies clinically.

And while gene sequencing has advanced at an astounding pace since its inception many decades ago, it’s taken years for broad genomic unraveling to reach the clinic.

Microarray assays are commonplace in clinical care. These are tests that identify deletions or duplications of chromosome segments, called copy number variants or CNVs. They’re traditionally the first-tier tests for many clinics when faced with developmental disease (DD) or intellectual diseases (ID), because a number of the more common DD/ID and autism conditions have deletions and duplications.

But with modern scientific advances, sequencing a patient’s entire tangle of DNA – or “whole genome sequencing,” as it’s called – or “whole exome sequencing” – referring to just the stretches of DNA that encode for proteins – can greatly improve and hasten the recognition of genetic risk factors for disease; and in turn, get a patient on an effective treatment more quickly.  

Whole genome and exome sequencing can help pinpoint single nucleotide variants (SNVs) or single-point mutations in an array of genetic conditions, including those that affect the heart and brain. Test results can be particularly useful in the pediatric population, in whom developmental disorders are a major concern and easily identifiable, or in “broad presentation” – when the patient’s clinical presentation is syndromic, or could fall under many different diagnoses. 

Yet an impediment to broad genetic testing in children suspected of having an inherited disorder has been reimbursement. Many insurance providers are reluctant to cover whole genome sequencing or exome sequencing, since testing for a specific mutation or genetic aberration was traditionally cheaper.

But with advances in genomic science, broad genetic testing in children with possible cognitive disabilities may be an easier clinical and emotional path for both them and their families.

Rather than undergo multiple, more focused genetic tests – a process that often lasts years before finding a diagnosis — one visit to the doctor administering a single broad genetic test could provide all of the necessary diagnostic information. This approach can help patients and parents shorten their ‘diagnostic journey,’ as PerkinElmer Associate Project Manager Hannah Lilligren put it.

“Whole genome sequencing is a single test that could provide a diagnosis,” she explains. “Multiple panels and assays could elongate an already arduous diagnostic journey and contribute to more worry, stress, and ineffective clinical management.” 

Lilligren adds that wider genome sequencing can save money in the long run.

In 2021, guidelines issued by the American College of Medical Genetics and Genomics recommended exome and genome sequencing as a first- or second-tier test for patients with congenital anomalies with onset prior to age 1, or developmental delay or intellectual disability with onset prior to age 18 years.

Numerous genetic risk factors have been linked with conditions like autism spectrum disorder and pediatric epilepsy, and increasingly complete genomic panels are being embraced by professional guidelines.

PerkinElmer Product Manager Jill Tapper says that even in the recent past many neurologic and developmental conditions were thought to be due to a single ‘point’ mutation, or to perhaps a few genetic blips that together cause a congenital condition. “But that’s just not the case anymore,” she says. “These disorders are often more complicated than that, and our technology has come very far.”

Tapper explains that conditions like autism can be viewed much like cancer. These are ‘umbrella’ terms that describe a very wide range of disorders affected by countless biological, genetic, and environmental risk factors.

“These are disorder spectrums that could be defined phenotypically and genetically in a million different ways,” says Tapper. “And analyzing a whole genome can now help provide a distinct diagnosis in many of these cases.”

Even a decade ago, accessing resources for a child with autism was a challenge.

Thankfully this is changing.

The ultimate hope in expanding genetic testing in children is helping identify, diagnose, and manage both physical and developmental disorders.

Using genomics to identify children who may benefit or respond to a given therapy could go a long way to help better pediatric care.