Anophthalmia

Anophthalmia
Specialty	Medical genetics

Anophthalmia, also known as anophthalmos (Greek: ανόφθαλμος, "without eye"), is the congenital absence of one or both eyes. It is a medical term that describes the lack of eye of occular tissue and globe from the eye. The absence of the eye will cause a small bony orbit, a constricted mucosal socket, short eyelids, reduced palpebral fissure and malar hypoplasia. Anophthalmia can be congenital or it can be acquired later in life. Genetic mutations, chromosomal abnormalities, and prenatal environment can all cause anophthalmia. Anophthalmia is an extremely rare disease and is mostly rooted in genetic abnormalities. It can also be associated with other syndromes.

Epidemiology

Anophthalmia has been reported to be present in 3 out of every 100,000 births. Many instances of anophthalmia also occur with microphthalmia. A recent study in England indicated that anophthalmia and microphthalmia had a combined average of 1 in every 10,000 births. The annual rate of occurrence of anophthalmia/microphthalmia in the United States is about 780 children born/year. Parents that already have a child who suffers from anophthalmia has a 1 in 8 chance of having another child with anophthalmia. Approximately 2/3 of all cases of anophthalmia are determined to be of genetic basis. Anophthalmia is one of the leading causes of congenital blindness and accounts for 3-11% of blindness in children. Anophthalmia and microphthalmia together make up 1.7-1.8% of reconstructive surgical cases in laboratory of plastic surgery and ocular prostheses.

Causes

Sox2 gene

The most genetic based cause for anophthalmia is caused by the Sox2 gene. Sox2 anophthalmia syndrome is caused by a mutation in the Sox2 gene that does not allow it to produce the Sox2 protein that regulates the activity of other genes by binding to certain regions of DNA. Without this Sox2 protein, the activity of genes that is impotant for the development of the eye is disrupted. Sox2 anophthalmia syndrome is an autosomal dominant inheritance, but the majority of patients who suffer from Sox2 anophthalmia are the first in their family history to have this mutation. In certain cases, one parent will possess the mutated gene only in their egg or sperm cell and the offspring will inherit it through that. This is called germline mosaicism.. There are at least 33 mutations in the Sox2 gene that have been known to cause anophthalmia. Some of these gene mutations will cause the Sox2 protein not to be formed, while other mutations will yield a non-functional version of this protein.

Other Influential Genes

Sox2 is not the only gene that can cause anophthalmia. Other important genes include OTX2, CHX10 and RAX. Each of these genes are an important in retinal expression. Mutations in these genes can cause a failure of retinal differentiation, which will OTX2 is dominantly inherited and varies in severity. It has also been linked with microphthalmia. BMP4 is also linked in anophthalmia is also a cause of myopia, microphthalmia and is dominantly inherited. BMP4 interacts with Sonic Hedgehog pathway and can cause anophthalmia.

Environmental Influence

Many environmental conditions have also been known to cause anophthalmia. The strongest support for environmental causes has been studies where children have had gestational-acquired infections. These infections are typically viral. A few known viruses that can cause anophthalmia are toxiplasmosis, rubella, and certain strands of the flu virus. Other known environmental conditions that have led to anophthalmia are maternal vitamin A deficiency, exposure to X-rays during gestation, solvent misuse, and exposure to thalidomide.

Chromosome 14

An interstitial deletion of chromosome 14 has been known to occasionally be the source of anophthalmia. The deletion of this region of chromosome has also been associated with patients having a small tongue, and high arched palate, developmental and growth retardation, undescended testes with a micropenis, and hypothyroidism. The region that has been deleted is region q22.1-q22.3. This confirms that region 22 on chromosome 14 influences the development of the eye.

Classifications

There are three classifications for this condition:

• Primary anophthalmia is a complete absence of eye tissue due to a failure of the part of the brain that forms the eye.
• Secondary anophthalmia the eye starts to develop and for some reason stops, leaving the infant with only residual eye tissue or extremely small eyes which can only be seen under close examination.
• Degenerative anophthalmia the eye started to form and, for some reason, degenerated. One reason for this occurring could be a lack of blood supply to the eye

Prenatal Diagnosis

Ultrasounds

Ultrasounds can be used to diagnose anophthalmia during gestation. Due to the resolution of the ultrasound, however, it is hard to diagnose it until the second trimester. The earliest to detect anophthalmia this way is approximately 20 weeks. 3D and 4D ultrasounds have proven to be more accurate at viewing the fetus's eyes during pregnancy and are another alternative to the standard ultrasound.

Amniocentesis

It is possible to diagnose prenatally with amniocentesis, but it may not show a correct negative result. Amniocentesis can only diagnose anophthalmia when there is a chromosomal abnormality. Chromosomal abnormalities are only a minority of cases of anophthalmia.

Postnatal diagnosis

MRI/CT

MRIs and CTs can be used to scan the brain and orbits. Clinicians use this to assess the internal structures of the globe, the optic nerve and extraocular muscles, and brain anatomy.

Examination

Physicians, specifically ophthalmologists, can examine the child and give a correct diagnosis. Some will do molecular genetics tests to see if the cause is linked with gene mutations.

Associations

There are a few conditions that are associated with Anophthalmia. These include:

• Trisomy 13
• Lenz Syndrome
• Goldenhar-Gorlin Syndrome
• Waardenberg Syndrome

Aside from these associative conditions, anophthalmia in only one eye tends to be associated with complications in the other eye. These risks include a higher chance of having glaucoma or a detached retina.

Treatments

Prosthetic eye

Currently, there is not a treatment option for regaining vision by developing a new eye. There are, however, cosmetic options so the absence of the eye is not as noticeable. Typically, the child will need to go to prosthetic specialist to have conformers fitted into the eye. Conformers are made of clear plastic and are fitted into the socket to promote socket growth and expansion. As the child's face grows and develops, the conformer will need to be changed. Expander may also be needed in anophthalmia to expand the socket that is present. The conformer is changed every few weeks the first two years of life. After that, a painted prosthetic eye can be fitted for the child's socket. . The prosthetic eye can be cleaned with mild baby soap and water. Rubbing alcohol should be avoided because it may damage the prosthetic eye. Children need to be checked regularly to ensure the fit and size is appropriate.

Cosmetic Surgery

If the proper actions are not taken to expand the orbit, many physical deformities can appear. It is important that if these deformities do appear, that surgery is not done until at least the first two years of life. Many people get eye surgery, such as upper eyelid ptosis surgery and lower eyelid tightening. These surgeries can restore the function of the surrounding structures like the eyelid in order to create the best appearance possible. This is more common with people who have degenerative apohthalmia.

External links

• MAPS Parent Support group for parents with Anophthalmic and Microphthalmic children
• http://www.anophthalmia.org/ ICAN - International Children's Anophthalmia and Microphthalmia Network
• Anophthalmia and Microphthalmia Resource Guide from the National Eye Institute (NEI).
• GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview
• MACS The Micro and Anophthalmic Children's Society - Offers support and Information to families in the UK and around the world
• ABC News video of Brielle Garrison, a young infant born with the condition.