The Craniofacial Development Group investigates the mechanisms of normal craniofacial development and how these processes are altered to cause craniofacial defects. The group is also interested in the origins of birth defects generally, since many birth defect syndromes involve multiple organ systems.
A baby born with a serious health issue has a huge impact on the family and can also have profound consequences for the child as it grows. Here Peter Farlie, Craniofacial Research Group Leader explains how understanding the way that embryos form and grow allows us to understand what causes birth defects.
How can studying the embryo provide important insight into understanding the causes of birth defects?
All birth defects come about from errors that occur during the development of the embryo or foetus. Some of these occur during early stages when the embryo is very small and these tend to be quite severe. Other birth defects occur when many of the structures of the embryo have already formed and impact on the normal growth of particular structures.
Regardless of when the errors that result in birth defects occur, the birth of a baby with a serious health issue has a huge impact on the family and can also have profound consequences for the child as it grows. Understanding birth defects will only come about through understanding how embryos are formed and grow.
What common birth defects have been found to stem from the embryonic development stage?
There are many different kinds of birth defects. Some of the most common defects affect the formation and growth of the face.
One of the most common birth defects is cleft lip and palate. In this condition, the embryonic structures that form the upper jaw are unable to form a continuous bridge of bone and soft tissue resulting in a gap in the upper lip. In the mildest form of this condition, only the upper lip is affected. However, the gap in the upper lip can also extend up to the baby’s nose and may also involve a gap in the bone of the upper jaw and this bony gap can also extend into the roof of the mouth.
Cleft lip and palate is rarely life threatening in itself but the impact of this condition can be very complex. Simply feeding a newborn baby with cleft lip and palate can be difficult. This is an issue that can cause enormous distress for parents trying to care for their baby and may have impacts on the growth of the baby.
Children with cleft lip and palate will often undergo multiple surgeries throughout their childhood to make their mouth function properly. Later in life cleft lip and palate can cause difficulties in learning to speak and may also cause problems with the growth of teeth.
As children grow, looking different to their peers can cause serious self-esteem issues and this can extend well into the teenage years, resulting in difficulties in social interactions and even academic performance. So even though our work focuses on understanding how these conditions occur, it is important to appreciate that the formation of the defect sets off a series of challenges that requires the involvement of a multidisciplinary team that will work with the child and family from birth but will likely extend all the way into adulthood.
How do these defects occur?
This is the question that we spend all our time trying to answer. There are many different reasons why birth defects occur and identifying the reason for the defect is just the first step in understanding the series of events that result in a particular condition.
Birth defects can occur from environmental insults such as chemicals or even very stressful events during pregnancy. This is of course why pregnant women restrict their intake of alcohol and increase their levels of folate for example.
The other causes of birth defects are altered genes. This is the area we focus on. Genes coordinate the complex events that are required to create a baby from a single cell. An error in any one of the thousands of genes involved in this process can result in a particular birth defect. The challenge is to understand how embryos form normally and then to identify the defective gene and how the altered gene changes the way the embryo develops. In cleft lip and palate for example, we know some of the genes that are involved. It turns out the way they function is quite complex. Sometimes they alter the way the different parts of the face stick together, sometimes they reduce the number of cells produced that build up the structures of the face. There are still so many unanswered questions.
How can this knowledge translate to helping kids who are born with these defects?
Fifty years ago, many types of cancer were fatal. Now, many of these once fatal conditions can be treated or managed and people survive. What happened over the past 50 years is we learned a lot about the causes of cancers and how to stop the cancers from growing and how to manage the disease clinically.
With birth defects we are still at the beginning of that journey. We need to learn a lot more about the genetic, biochemical and environmental causes of birth defects so we can design strategies to stop them from happening.
Fifty years ago it was inconceivable that many cancers could be stopped. But many very smart people worked very hard and changed that. We can’t cure all cancers, but we are a lot better off now than we were 50 years ago. The same can be true for birth defects.
What is the most interesting finding you have come across through your research on embryos?
I have been working with embryos my whole career and I never get tired of watching how incredibly resilient they are. There are so many opportunities for things to go wrong, yet mostly they do very well and a normal, healthy baby is born. Nature has endowed embryos with a whole arsenal of tricks to fix up problems as they arise. The most exciting thing about working with embryos is learning how they do this and working out ways that we can help them when they are faced with a problem they can’t deal with.