Genetic Issues With A/M

The eye is affected in about one-quarter of all inherited diseases, thus possible genetic causes of eye malformations must be considered. Congenital A/M can occur alone or with other birth differences. Geneticists use unusual findings in the eye, as well as other findings throughout the body, to help identify possible syndromes or causes of the disorder in an individual.

A/M has many different potential causes, including genetic conditions such as chromosomal disorders and single gene disorders.

Chromosomes are tiny structures that carry our genetic information and are arranged in 23 pairs in each cell of the body. One chromosome of each pair comes from the mother and the other from the father.  Each chromosome consists of thousands of genes, which are made up of DNA. The DNA is the genetic "alphabet" consisting of four letters: A, C, T and G. These letters create a series of three-letter "words" that combine and make up genes. Each gene has a specific function to encode the directions for the production of proteins in our bodies. Proteins are elements that do the different jobs our bodies require. A change in any of these "words" is known as a mutation. A mutation can lead to either abnormally made proteins or absence of the protein which then affects the development of the fetus during pregnancy.

Single gene disorders occur as a result of a mutation in one gene on one or both of the chromosomes of a pair. This mutation changes the genetic information and therefore the blueprint for development, which leads to disease or birth defects.

Chromosomal disorders involve extra or missing chromosomes, or rearranged pieces of chromosomes. This extra or missing information changes the blueprint for development. Because each chromosome houses thousands of genes, a normal chromosome result cannot tell us if all the genes are working properly. It simply tells us there are no large pieces of chromosomes that are extra, missing or rearranged.

Sometimes, we cannot identify a syndrome in an individual to help explain the cause of A/M. Researchers are currently working on locating the gene or genes involved in normal eye development, which may lead to many answers about anophthalmia and enable geneticists to provide more accurate counseling and recurrence risks.

Identifying Genes that may cause anophthalmia, microphthalmia and coloboma

Development of the eye during pregnancy is a very complex process.  Many genes are involved in ensuring that the sequence of this development occurs as it should.  The eye is completely developed in the first trimester of pregnancy. 

There are many known causes of anophthalmia, microphthalmia and coloboma including genetic conditions and prenatal exposures to infections and medicines.  However, in most cases the cause is unclear.

Genetic research

Researchers around the world are working to identify the genes involved in the normal development of the eye.  Many genes have been found to have a role in this complicated process.  Changes in these genes, also known as mutations, can cause the gene to not work properly causing abnormal development of the eye.

Most changes (mutations) in a gene have occurred for the first time in the individuals with anophthalmia/microphthamia. In other words there is no family history of the condition. This does not mean the cause is not genetic.

Identifying the cause of the eye defect is important in terms of management of the individual medically and educationally. In addition, risks for recurrence differ based on the reason that the eye defect occurred.

SOX2 Gene

This gene was identified several years ago by researchers in England.  Changes (mutations) in this gene have been found in about 15% of individuals with anophthalmia/microphthalmia.  Typically an individuals has 2 working copies of this gene. If one copy is changed (mutated) it leads to anophthalmia/microphthalmia.  Genetic testing is available for SOX2 and should be ordered on anyone with anophthalmia or microphthalmia.  If you need help getting this test done call Tanya Bardakjian 215-456-8726 or e-mail bardakjiant@einstein.edu.

Other Studies

There are many other genes involved in the development of the eye and mutations have been identified in many of them.  Dr. Adele Schneider and Tanya Bardakjian, MS  have been collecting DNA samples and clinical information on individuals with anophthlamia, microphthalmia and coloboma through the A/M Registry Research Project.  These samples will be screened for changes in the known genes.  Results are made available to families if a mutation is identified. 

Please contact Tanya Bardakjian at bardakjiant@einstein.edu or call 215-456-8726 of you want more information or if you have any questions.