What have we learnt in the second Folbigg inquiry, and what happens now?

This article contains subject matter some readers may find distressing. If you or someone you know needs help with mental health, contact Lifeline on 13 11 14 and Beyond Blue on 1300 224 636. Red Nose Australia provides 24/7 bereavement and counselling services for those affected by the loss of a child on 1300 308 307.

Science has faced an unprecedented test in New South Wales this past fortnight, with experts from across the globe called to give their insights as part of the inquiry into Kathleen Folbigg’s convictions.

Now adjourned, the inquiry will reconvene in April when presiding judicial officer Tom Bathurst hears closing submissions before finalising his report and recommendations.

He will consider the evidence now given by multiple geneticists, protein scientists, cardiologists, paediatricians, neurologists, forensic pathologists and psychologists – a bonanza of expertise rarely, if ever seen, in a judicial inquiry in Australia.

In 2003, Kathleen Folbigg was convicted of killing her four children Caleb, Patrick, Sarah and Laura. She has so far served 20 years of her sentence, and will be eligible for parole in 2028. Folbigg has always maintained her innocence.

Her supporters secured a judicial review in 2019 when new forensic pathology evidence was heard, but it came to nothing.

The current inquiry was called following research published in 2021 into a newly-discovered variant of a gene which produces calmodulin, a functional protein.

According to this research and subsequent tests into its function, the variant reduces the body’s ability to properly regulate calcium and sodium ions in heart cells. Only Kathleen Folbigg and her two deceased daughters possess the gene, which was uncovered by experts during the 2019 enquiry.

One of those experts – Professor Carola Vinuesa – assembled an international team to study the variant. The report they produced points to this variant as an explanation for Sarah and Laura’s deaths.

A fate sealed in the genes? The research into CALM2 G114R

The inquiry first heard from the Danish scientists who discovered the existence of calmodulin gene mutations a decade ago.

Mette Nyegaard and Michael Toft Overgaard expressed their view that no variation to any of the three calmodulin-coding genes – CALM1, CALM2 and CALM3 – could be considered benign, due to the protein’s role in regulating the heart’s ion exchange. This process elicits the human heartbeat.

In Kathleen Folbigg, the CALM2 gene she passed onto the girls was found to have mutated at position 114, replacing the smallest amino acid glycine with the second-largest, arginine. This is the position where calmodulin proteins normally bind to sodium ion channels in heart cells, meaning the final, so-called ‘Folbigg variant’ (technically CALM2 G114R) is impeded in this task.

The subsequent misregulation of sodium, they say, could give rise to irregular heartbeats in children.

Why proteins matter

The contest of expert opinion in this inquiry has revolved around whether this mutation, and forensic pathology and psychology appraisals of existing evidence, casts a reasonable doubt on Folbigg’s convictions.

The team behind the 2021 research article that sparked the inquiry has emphasised the mutation is “ultra rare”. In her analysis, Nyegaard emphasised that naturally occurring variations to the CALM2 gene rarely occur in humans.

Vinuesa and colleagues Matthew Cook and Todor Arsov – the team that conducted the first in-depth investigations into the Folbigg variant – emphasised calmodulin is highly-conserved (that means it shouldn’t mutate) at the 114 position. Calmodulin itself is identical across all vertebrate species, but glycine is almost invariably produced at 114 in most animals, some plants and even fungi.

Arginine appearing at that position in Kathleen, Sarah and Laura, is unprecedented in humans.

Folbigg amino acids
Glycine, the smallest of the 20 amino acids, is replaced by tryptophan (the largest) in the known disease-causing G114W variant and by arginine (the second largest) in the Folbigg G114R variant. Credit: image generated with iQmol

They also pointed to an adolescent fainting episode where Folbigg passed out after a swimming race, as a possible example of CPVT (or catecholaminergic polymorphic ventricular tachycardia).

CPVT is a known calmodulinopathy – a disease caused by irregular calmodulin – which triggers heart arrythmia during times of exercise or stress.

G114R is not the only variant of interest though.

The two Folbigg boys were found to have inherited a rare variant to the BSN gene. In reporting on this finding, Vinuesa highlighted emerging research that shows the onset of epileptic characteristics in mice with the gene. It was suggested that Patrick, Kathleen’s second child, died in part due to his own epileptic condition.

Indeed when questioned on that topic, paediatric neurologist turned parliamentarian Dr Monique Ryan affirmed her view – presented at the original inquiry in 2019 – that Patrick’s death could be explained by seizures he experienced as a result of epilepsy. In the months before his death, Patrick suffered an acute life threatening event after a seizure. Ryan indicated this event marked the onset of his epilepsy.

The Folbigg variant research was also critiqued throughout the course of the hearings.

Professor Edwin Kirk is a clinical geneticist who was part of another team that decoded the genomes of the Folbigg children in 2019. Back then, he determined the variant to be one of unknown significance – a standard used to describe gene mutations where it isn’t clear whether they are benign or disease-causing.

How scientists decide which mutations in your DNA are deadly

He maintained that view at this inquiry, but was open-minded about the possibility of CPVT being a possible indicator of a phenotype (a term used to describe characteristics of disease resulting from a variant interacting with its environment).

Carola todor
Professor Carola Vinuesa (left) and Professor Todor Arsov (left-centre) enter the inquiry at the Chief Secretary’s Building in Sydney. Credit: Supplied

He also agreed the inquiry, as recommended by the Vinuesa team, should consider a near-identical variant (G114W) as relevant, when deciding on the Folbigg mutation’s pathogenicity.

G114W was found to have caused a death and a cardiac arrest in an American brother-sister pair.

On the other hand, Dr Dominic Abrams – a cardiovascular geneticist based in Boston (USA) – felt that while the variant could explain the deaths, he believed it ultimately “unproven and uncertain” that it had.

His view, like those of Kirk and Dr Calum MacRae who presented a similar viewpoint last week, relates to uncertainty that Kathleen Folbigg has the clear characteristics associated with a calmodulinopathy phenotype.

Meadow’s Law and the assumptions that put innocent women behind bars

Largely, Folbigg’s cardiac history shows no signs of disease, except for a few anecdotal fainting instances that could suggest CPVT or another arrythmia phenotype.

In answer to those questions, Arsov and Vinuesa elaborated on the concept of penetrance, the nature of gene variants inconsistently manifesting expected phenotypes; and variable expressivity, the fact that mutations don’t always present the same symptoms in everyone to possess them.

In science, agreement isn’t a given

The very nature of science – particularly when many branches interact – is that scientists often fail to agree.

That’s the case in this Folbigg inquiry, and the challenge for Tom Bathurst will be to determine what expert evidence to consider.

It didn’t stop with the genetics.

Dr Allan Cala, the forensic pathologist who examined Laura after she died, again asserted his view that the four deaths – by all accounts exceedingly rare in one family – should be considered as the possible result of inflicted injury.

Other forensic pathologists disagreed. Professor Stephen Cordner – whose retrospective forensic assessment triggered the 2019 inquiry – and Dr Matthew Orde, declared the absence of injuries on the children made it difficult to conclude deliberate suffocation, as proposed by prosecutors in the trial.

In the 2019 inquiry, other pathologists who presented their assessments of the four deaths shared that view.

Professor Peter Fleming, a world-renowned expert in sudden infant death syndrome, strongly emphasised his view that while forced suffocation may leave no signs of injury, as argued by Cala, he would expect to find injuries in older children like Sarah and Laura.

SIDS expert says it would be extraordinary for someone to kill Folbigg children without leaving a mark

Then there’s the diaries.

Three psychology experts examined the complete set of Folbigg’s diaries. Only extracts were viewed at the trial.

They concluded that Folbigg’s writing indicates signs of certain mental health disorders, that the entries used to convict her are largely expressions of maternal grief and, notably, none of them indicate intent to kill her children.

Tom bathurst
The Hon Tom Bathurst KC has presided over this Folbigg Inquiry. Credit: Supplied

Where to from here?

For science in Australia, this inquiry is probably unprecedented. Rarely has evidence from world-leading geneticists, cardiologists, neurologists, paediatricians, forensic pathologists, and psychologists, been heard in the same place.

It is surely the first time a piece of research, led by scientists working in Australia, has triggered a Governor’s inquiry.

The Australian Academy of Science – acting as an independent scientific advisor to this inquiry – hopes this could lead to law reform and allow, when new scientific findings come to hand, appeals to be considered when traditional avenues are exhausted.

Can justice keep up with science?

But the matter before Tom Bathurst is to carefully weigh the evidence – from points agreed on by all of the experts, to those where there has been marked disagreement.

Does the absence of a clear cardiac phenotype in Kathleen Folbigg preclude the possibility that she’s a rare person who has lived life without her deadly gene expressing itself? Has that gene remained hidden in the mother while potentially causing the death of her girls?

Is the suggestion that Patrick’s epilepsy caused his death, or that no obvious signs of suffocation-related injury were found on the children, enough to cast a reasonable doubt on her convictions?

What weight will be put on the diary evaluations?

If any of these is enough to convince Bathurst of a reasonable doubt that Folbigg caused any of the children’s deaths, he could recommend the Court of Appeal quash her convictions.

But if Bathurst is unconvinced, Folbigg will remain in prison until at least 2028.

The inquiry has adjourned until April where closing submissions will be heard. In the meantime, science observers will study what the experts have said, and wait to see what the justice system decides in Bathurst’s final report.

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