New genes identified as causing a common physical abnormality

The craniofacial condition has long been considered to be caused by a combination of common genetic variants and environmental factors. Each contribute to a small amount to the risk of a child being born with the abnormality.

Researchers have discovered that the genes hide proteins that work together, which provides a significant breakthrough into the biological reasons behind the development of the malformation.

Cleft lip/palate occurs in one in 800 children. It develops when part of the lip or roof of the mouth (palate) does not form properly. This leaves a gap (cleft). These birth defects occur in early pregnancy. 

There is also a greater chance of having a child with cleft lip or palate if a parent of sibling has one.

The research project was led by Sydney Children’s Hospital clinical genetics specialist, Associate Professor Tony Roscioli, from the Centre for Research Excellence in Neurocognitive Disorders at Neuroscience Research Australia (NeuRA).

He collaborated with the University of NSW, Seattle Children’s Research Institute and the University of Washington School of Medicine in the US.

Published in the American Journal of Human Genetics, the study provides the first evidence that a significant number of non-syndromic clefts have a single gene basis.

Variants in these genes were found to account for 15 per cent of the families who took part in the study.

Associate Professor Roscoli says about 250 Australian children each year and one affected child born every three minutes worldwide have cleft lip/palate.

“What we were seeking to identify in this study was whether single genes could cause a cleft lip or palate in families where there were multiple affected people,” he said.

“Knowing the genes and the way these impact lip and palate formation opens the door for further research to understand how these genes work and to develop treatments.”

Nine-month-old baby Riley was born with cleft lip and palate.

He had corrective surgery in April this year when he was five months of age. Next month he will have another operation – one of several before he begins school.

His parents, Rhiannon, 27, and Aidan, 31, of Barden Ridge, were asked to provide their family history during the 20-week scan.

Mrs Bell’s sister had cleft lip as a baby, but the couple did not think their child would inherit the condition.

“We didn’t even think about it as something we’d potentially have to deal with,” Mrs Bell said.

“Our 12-week scan was perfect so I didn’t feel nervous going into the 20-week ultrasound. It was a shock. We were told with the condition there is often a chromosomal disorder, but we got the amazing news it was an isolated issue. We then spent the next few months preparing for the special care Riley would need once he was born.”

Riley was born about five weeks premature at Kareena Private Hospital, and was in the special care nursery for four weeks. He was fed through a nasal tube and began to learn how to feed from a special bottle.

Mrs Bell said she was unsure whether the couple would give Riley a sibling, knowing there was a chance another child could develop the abnormality.

“We always wanted two kids but we were undecided if we’d have another because we were unsure if we wanted to risk putting another baby through what Riley has had to go through,” Mrs Bell said. “Our risk is low but it can’t be guaranteed.

“This research gives us a bit more hope and we want to volunteer to be involved in more research to help other people  – and us in the future.”

Associate Professor Roscoli says future research will further investigate the biology and link the findings to future potential therapies. 

“Importantly, we also showed that some affected individuals in this study had a gene variant which was inherited from neither parent – that is, it likely arose spontaneously in the affected individual during early development – and therefore the parents were able to be reassured of a very low chance of having another affected child,” he said.