Cleft Lip & Palate

Research identifying the causes for cleft lip and palate

Overview

Cleft lip and palate is one of the most common birth defects, occurring in around 1 in 650 children. It most frequently occurs in individuals who carry small changes in a number of different genes which influence the development of the cleft lip and palate. Environment factors during pregnancy such as maternal alcohol intake and smoking can also have an influence. In a smaller number of clefts patients there are also stronger genetic factors.

Our research is around management and treatments for cleft lip and palate and we aim to understand the genetic and environmental causes of clefting.

Problem

Although cleft lip and palate often occurs as an isolated finding, around 45 per cent of children who are born with an isolated cleft palate will also have other problems such as poor growth, delayed development or additional malformations. In these children, it is more likely to be a genetic causation and maybe be at risk of future medical and education problems.

Parents of children with these complex cleft conditions usually worry about their child’s future and whether a future child of theirs maybe be affected with similar problems. There are often concerns for their relatives as well. To try and understand the cause of cleft palate in these situations we have used newer types of genetic testing.

What we have achieved to date

One of our current projects is exploring the genetic basis of cleft palate by looking for tiny chromosome changes using microarray techniques or studying families with several members affected. This is done by identifying genetic information in common to find the genes involved in clefting, which is called autozygosity mapping and Next Generation sequencing. The genetic studies also extend to research into other palate function problems which cause indistinct speech such as velopharyngeal incompetence. A number of genetic changes have been identified in this latter group which have affected the way patients are managed or influenced genetic counselling.

Where a cleft is associated with other features and identifying the cause is difficult we have developed a web-based system of seeking expert opinions to aid diagnosis. An example of this research is the study of the young girl pictured who was presented with cleft lip and palate, with no family history of clefting or pregnancy complications. The child also suffered from gastro-oesophageal reflux and poor weight gain, it soon became clear that she was also delayed with her development. A routine chromosome analysis showed normal results so the child was referred to the genetic clinic. Further chromosome tests ruled out a deletion of chromosome 22 and a deletion of chromosome 1p36. An MRI scan of the child’s brain showed some non-specific changes.

The child was enrolled into our research study to look for small chromosomal changes in children with cleft syndromes. Detailed examination of the chromosomes using microarray analysis which revealed that she had a small 4.5Mb deletion on chromosome 2 at 2q33.1. This region involved a gene called SATB2 which is implicated in cleft palate and explained her symptoms. Neither parent carried the chromosome change and went on to have another healthy baby, with the knowledge that the risk of recurrence in a future pregnancy was very low.

In addition we aim to learn more about the causes of clefting so that ultimately we can identify those who are at risk of having a child with a cleft and find ways to preventing this occurring.

What we aim to achieve

Our researchers have recently been involved in a successful bid to fund a UK Centre for Cleft Research. This centre will open on the Trust site in June 2011 and will seek research ideas from a Cleft Clinical Studies Group which includes parents as well as a number of professionals and develop them into rigorously designed studies with the aim of improving all aspects of cleft. By identifying a cause for cleft lip and palate in affected individuals we can provide information about the best medical care for them and also provide information for parents
on the cause of the problems and whether there is a risk to further pregnancies.