How a genomic diagnosis can change patient care

Genomic testing involves mapping a patient’s entire DNA sequence (their genome) and comparing it with a reference genome to identify changes that may cause disease.

It can be especially useful for differential diagnosis – when a patient’s symptoms match more than one condition. Identifying the genetic cause of these symptoms can enable doctors to prescribe treatments that are most likely to work, or give patients a better understanding of how their condition may progress.

Here are six examples of Victorian patients whose care was changed after receiving genomic testing through a Melbourne Genomics member hospital.

A simple reason for Ariana's complex symptoms

‘Ariana’* started to have seizures at eight months old, lost developmental skills, and would suddenly stop breathing.

Countless tests at The Royal Children’s Hospital failed to find a cause. It took a genomic test to identify a single-gene variant that made Ariana’s cells unable to transport riboflavin (vitamin B2) around her body. A regular dose of riboflavin eliminated the symptoms, and Ariana now lives a normal life.

Ariana was one of several cases that provided the evidence for rapid genomic testing of critically unwell children.

*Name changed for privacy purposes.

Are you a paediatrician in Victoria? Here’s how to order a Medicare-funded genomic test.

The insight that saved Tess's transplant

Tess* was scheduled for a kidney transplant, but wanted to know exactly why her kidneys were failing. Her nephrologist at Austin Health organised a genomic test, which turned out to be life-saving.

The test identified Primary Hyperoxaluria type 1, a genetic condition that caused Tess’s liver to pump excess amounts of a compound called oxalates into her kidneys. Had the transplant gone ahead without the test, Tess’s new kidney would have been poisoned in exactly the same way.

After the genomic test, Tess was re-booked for a liver and kidney transplant, and is progressing well.

Sparing Charlie from invasive tests and unnecessary medications

Charlie had breathing issues since birth, which doctors believed was due to a congenital heart condition. By age six, he’d also developed persistent chilblains, severe joint pains and was struggling to put on weight.

It was clear now that Charlie had an autoimmune condition, but diagnosis would likely involve biopsies and other invasive tests. Luckily, Monash Health recommended genomics as a first-line test. This identified a random mutation in Charlie’s STING1 gene, completely unrelated to his prior heart condition.

Common immunosuppressants do not work for this condition, so without the test, Charlie might have spent months cycling through different drugs and experiencing their side effects alongside his other symptoms. But now, Charlie is on a targeted treatment that has significantly improved his life expectancy and quality of life.

The source of the 'electrical fault' in Geoff's heart

When 66-year-old Geoff collapsed with heart palpitations, the Austin Health cardiology team identified an electrical fault that prevented his heart from pumping rhythmically.

Cardiologists initially suspected CVPT, a rare calcium defect, but organised a genomic test to be sure. The test identified the true cause: a variant in the KCNH2 gene that suppresses potassium ion activity in the heart. This meant Geoff could receive the correct treatment from the start, greatly reducing the likelihood of future heart problems.

Finding the truth when different cancers look the same

Susan discovered a lump on her ribcage. A CT scan showed Stage 4 cancer, spreading rapidly through the 65-year-old’s body. A biopsy of the biggest tumour suggested it was a sarcoma, but her oncologist at Ballarat Cancer Centre wanted to be sure. He referred Susan to the Peter MacCallum Cancer Centre for further tests.

Genomic sequencing of the tumour discovered its hidden nature – it was rare type of melanoma with an option for targeted treatment. After four sessions of immunotherapy, Susan’s tumours had shrunk to nothing. She will continue her immunotherapy course, but it’s now focussed on fighting off any recurrence of the cancer.

Victorian cancer hospitals are trialling different models of genomic care. Find out more.

Understanding Edward's options

Shortly after Edward was born, a renal ultrasound detected multiple cysts in his kidneys. Because there are many types of polycystic kidney disease, it was important to understand how Edward’s condition might progress.

Edward’s nephrologist at The Royal Children’s Hospital organised genomic tests for the boy and his parents. The test discovered a rare gene variant that was autosomal dominant – meaning that Edward is unlikely to need a kidney transplant until he reaches adulthood. He now has six-monthly kidney check-ups, but lives an otherwise normal life.

Bringing genomic testing into routine healthcare will mean thousands more Victorians can get accurate diagnoses, targeted care and ultimately, better outcomes.