Genetics and facial disfigurement

In the past, when a child was born with a facial disfigurement, nobody could explain why. Thankfully, scientific progress has shown that the causes of many congenital conditions are the result of genetics. We can now, more or less, explain why somebody has a facial disfigurement. This not only raises the hopes of prevention and cures, but also it helps to reduce the stigma and fear that many people experience when the encounter facial disfigurement. If something can be understood, then it is nothing to be feared.

The genetics of development

DNA is the code that tells your body how to grow itself and keep living. When a sperm fertilizes an egg, the DNA of the two parents combine and produce a new individual. As that egg grows into a foetus and then into a baby, the DNA inside tells the cells when and where to reproduce and what type of cells to grow into. There are billions of bits of code in human DNA, and it is very common for mutations to occur. Mutations are deletions or mistaken copies, or other errors in the DNA code that cause the gene to function differently. Most of the time, mutations don’t do anything. Sometimes they are very useful: it is how we evolved, in fact. Very rarely, a mutation can result in a visible difference, called a mutated phenotype. It is these mutations that cause congenital disfigurements.

Common congenital disfigurements

The most common congenital disfigurement in the UK is cleft lip and palate. Each year, about 45000 babies are born in the UK with cleft lip and palate. The genetic reasons that cause the face to grow with a cleft lip and palate are complex and not very well understood but we know that environment plays a large role as well. However, because of population studies, we know for sure that genes are involved. It is almost certain that sometime in the next 10 years we will discover why cleft lips and palates happen.

The next most common congenital disfigurement is port wine stains and haemangiomas. We know that they are genetic but we don’t know which genes are responsible. Because these conditions are not life-threatening and are usually treatable, that has not been very much research into the underlying causes of them. This is an oversight; port wine stains on the face can result in severe bullying and discrimination.

Rare genetic conditions

Craniosynostosis syndromes are a set of around 200 genetic disorders that are characterised by the skull not fusing and suturing properly during development. The two most common are Crouzon syndrome and Apert syndrome. Crouzon syndrome occurs roughly every 1 in 16 million births. Apert syndrome is more common, about one in 65,000 births resulting in the syndrome.

Apert syndrome causes the skull to fuse too early during development and impairs the development of the brain, skull and face. This can actually lead to significant developmental delays and other conditions such as epilepsy, as well as severe facial disfigurement. The genetics of Apert syndrome have been narrowed down to the fibroblast growth factor receptor-2 gene, or FGFR2. Parents can be carriers of this gene but most of the cases appear to be from random mutations. Mutations to this gene are also found in Crouzon, Jackson-Weiss syndrome, and Pfeiffer syndrome. Apert syndrome is the result of this single genetic difference.

Crouzon syndrome is very similar and is caused by the same gene being mutated, however at a different location. The effects are not as severe as for Apert syndrome: most people with this condition are of normal intelligence.

Other congenital facial deformations caused by this gene include Beare-Stevenson cutis gyrata syndrome and Saethre Chotzen syndrome. Fibroblast growth factors are essential for telling the body how to grow. When a mutation in the fibroblast growth factor receptors happens, the body gets confused signals and does not grow in the normal way.

Treacher Collins syndrome

Roughly 1 in 50,000 babies is born with Treacher Collins syndrome. This is a genetic disorder that causes the face to grow abnormally. It can result in small jaw bones and chins, small or missing ears, downward slanting eyelashes, and underdeveloped facial bones. Treacher Collins syndrome is usually caused by mutations in the TCOF1, POLR1C, or POLR1D genes; also some people have a similar phenotype but the genetic course has not been established. Like craniosynostosis syndromes, Treacher Collins syndrome is the result of genes that play very vital roles in the development of the bones and facial tissues being disrupted by mutation. An important signalling molecule, rRNA, is not produced in the same way in this condition, leading to confused signals during development.

Goldenhar and Moebius syndromes

Both Goldenhar syndrome and Moebius syndrome of these conditions are known to be genetic, at least in part, but it is not clear what the exact causes are.