Jun 29, 2007
Classic osteogenesis imperfecta (OI) is caused by a dominant gene, meaning anyone who inherits a copy will suffer from fragile bones - often fatally.
But a US National Institutes of Health team has found two recessive OI genes.
Carriers are healthy, but if two have a baby there is a one in four chance their child will have two bad copies, with potentially lethal consequences.
All of the eight babies and children studied by Dr Joan Marini, who had inherited two bad copies, suffered repeated broken bones and died from their condition.
None of the parents had shown any signs of the disease themselves as carriers.
The discovery of the two new genes - CRTAP, reported in the New England Journal of Medicine, and P3H1, reported in Nature Genetics - will have big implications for both genetic counselling and testing.
About 85% of OI cases can be explained by dominant genes that cause faulty collagen - a major component of bone.
For the other 15% of cases, doctors struggled to explain the cause and used to tell these families that the risk of having another child with the condition was very slim - around one in 15,000-20,000 - presuming that it was caused by a random mutation, and that any existing healthy children did not carry the gene.
Lead researcher Dr Joan Marini says essentially all of these cases are caused by the newly discovered recessive genes, which interact with collagen.
If so, this means the families would have a one in four chance of having another affected child.
And there would be a 50-50 chance that any of their children would be a carrier.
Dr Marini said: "Now it is very important that families with severe bone disease have molecular analysis to determine whether they have the dominant or the recessive form.
"It's important to parents and to siblings because they could be a hidden carrier."
There have been cases where babies suffering from milder forms of brittle bone disease have been taken into care - because the symptoms resemble those of child abuse.
Dr Marini said it was very unlikely that any suspected child abuse cases might instead be explained by the recessive genes she has discovered.
This is because carriers had no illness and those who inherited two bad copies had severe disease with injuries that would never be mistaken for abuse.
But she said it was conceivable that carriers of yet to be discovered recessive OI genes, of which she believes there could be many, might.
A spokeswoman from the Osteogenesis Imperfecta Foundation said: "This changes how we view the condition and it's answered many questions.
"People were baffled in the past by cases where couples with no family history of severe OI went on to have two or more affected children. The recessive genes can explain this."