Experts have identified a genetic trait which triples the risk of a baby having a cleft palate in families where a child is already affected.
Babies with cleft lip and palate are given corrective surgery
US researchers said the discovery means it could be possible to screen parents to see if further children are likely to be affected.
They said it would also have important implications for offering families genetic counselling.
The research is published in the New England Journal of Medicine.
The team studied the DNA of 1,968 families - around 8,000 people - with a history of isolated clefts, from 10 countries.
They discovered nine variations, called single nucleotide polymorphisms, (SNPs), in and around the IRF6 gene, which acted as genetic signposts of cleft lip or palate risk.
The scientists say genetic screening for the variants would detect around 12% of cases of isolated cleft lip and palate - where the child is not affected by any other conditions.
The team had previously found another gene which accounts for around 2%.
Around one in every 700 children in the UK are affected by cleft palate. Around 70% of cases are isolated cleft lip or palate.
A cleft is an opening or separation in a body structure. Clefts that occur in the oral-facial region often involve the upper lip, the roof of the mouth (hard palate), or the soft tissue in the back of the mouth (soft palate).
Children with the condition can have problems chewing, swallowing, and speaking, and are prone to frequent ear infections that can lead to hearing loss. Dental problems may also occur.
Surgery can help, but it may not be a not a complete solution.
Recent research also suggested isolated clefts were linked to an overall increase in the risk of premature death from all causes.
Nancy Green, medical director of the March of Dimes, which helped fund the study, said: "This new finding brings us closer to understanding the multiple genetic factors underlying these very serious birth defects, with probable environmental effects."
She added: "A special strength of this study is that its findings come from a variety of ethnic groups, including Europeans, South Americans, and Asians.
"This gives us confidence that the linkage of this gene variant to oral clefts is true across different populations in the US and worldwide."
Gareth Davies, chief executive of the UK's Cleft Lip and Palate Association, told BBC News Online: "If there is a genetic risk in some families of having a cleft, that would be good to know.
"There have been certain things which have been shown to possibly reduce the risk, such as taking large doses of folic acid before and during pregnancy."
He said babies born with the condition had to undergo three operations, the first at birth and the last at around the age of eight or nine.
They can also require orthodontic work and speech therapy.
Mr Davies added: "In terms of self-esteem, if a child has a serious disfigurement, they may find social situations more difficult."