by Dan Roberts
October 2002
Several types of macular degeneration affecting children, teenagers, or adults are commonly known as early onset or juvenile MD. Many of these types are hereditary and are looked upon as macular dystrophies instead of degeneration. “Degeneration” is the term used for descriptions of the diseases of age related macular degeneration, which is more common in the older generation.
Macular dystrophy is a condition which appears earlier in life, and causes a reduction in central vision found in the macula, the central portion of the retina. Macular dystrophies are usually inherited in a predictable pattern within families. There is a genetically determined abnormality causing either the loss of the normal pigment associated with the photoreceptors in the retina or the accumulation of an abnormal protein. Some examples of macular dystrophies are:
Cone-Rod Dystrophy
Patients with cone-rod dystrophy first experience central vision loss, followed by night blindness and peripheral vision loss. Central vision loss begins in the first decade of life with the onset of night blindness occurring sometime after age 20. Little visual function remains after the age of 50.
Corneal Dystrophy
The globe of the eye is made of five layers, and the cornea is the transparent front portion. Corneal dystrophies form a group of rare disorders which usually affect both eyes. They may be present at birth, but more frequently develop during adolescence and progress gradually throughout life. Some forms of this dystrophy are mild, while others are more severe.
Fuch’s Dystrophy
Fuchs’ dystrophy is a slowly progressing disease, affecting the cornea, and usually affects both eyes. It is slightly more common in women than in men. Although doctors can often see early signs of Fuchs’ dystrophy in people in their 30s and 40s, the disease rarely affects vision until people reach their 50s and 60s. It is a major cause for corneal transplantation.
Sorsby’s Macular Dystrophy
Sorsby disease is also called macular cyst, or cystoid macular degeneration. Symptoms usually begin between 20 and 40 years of age. This form of the disorder is marked by impairment of vision, possible color vision abnormality, and can be progressive in nature.
These macular dystrophies have different genetic influences or ways of inheritance. Some may be passed on in autosomal dominant patterns (Best disease) which means that both parents and their children may be affected. Others can be inherited as an autosomal recessive pattern (Stargardt’s disease) which usually starts in adolescence. Still others can be passed on as an x-linked trait (juvenile retinoschisis), which is carried by females and affects males only.
Best Disease
Best disease (also known as vitelliform macular dystrophy) affects the macula, the central part of the retina responsible for fine visual detail and color perception. It is usually diagnosed during early childhood or adolescence.
In the early stages a yellow cyst forms under the retinal pigment epithelius (RPE) beneath the macula. Despite the presence of the cyst, visual acuity could remain nearly normal, 20/30 to 20/50, for many years. Peripheral vision usually remains unaffected. With many people, the cyst will eventually rupture while fluid and yellow deposits spread throughout the macula. The macula and the underlying RPE begin to atrophy causing further vision loss, to about 20/100 later in life. Best disease does not always affect both eyes equally.
This disease is passed through families by the autosomal dominant pattern of inheritance, which means that an affected individual has one Best gene paired with one normal gene. When an affected person has children with an unaffected partner, there is a 50% chance that the affected parent will pass the disease-causing gene to each child. A child who does not have the Best disease gene will not have the disease, and therefore cannot pass this disease on to his/her children.
Currently, there is no treatment for Best disease. A gene has already been mapped to a human chromosome and hopefully will be soon identified as to its function in the retina.
Links to additional information about Best Disease:
Detailed Article on Best Disease
Genetics of Best Disease
Stargardt Disease
Stargardt disease is the most common form of inherited juvenile degeneration. It is characterized by a reduction of central vision, but preserves peripheral vision. It is usually diagnosed in individuals under the age of 20 when decreased central vision is first noticed.
The retina will show a macular lesion surrounded by yellow-white spots with irregular shapes. The retina consists of layers of light sensing cells that line the inner back wall of the eye. The progression of vision loss is variable and can start with a visual acuity of 20/40 and decrease to 20/200 (legal Blindness). By age 50, approximately 50% of all those studied in clinical trials had visual acuities of 20/200 to 20/400. In late stages of this disease there may also be color vision impairment.
In 1997, researchers isolated the gene for Stargardt disease. The ABCR4 gene produces a protein involved in energy transport to and from photoreceptor cells in the retina. Mutations in the ABCR4 gene, which cause Stargardt disease, produce a dysfunctional protein that cannot perform its transport function. As a result, photoreceptor cells degenerate and vision loss occurs. This discovery allows researchers to study the underlying biochemical interactions that result from mutations in this gene.
Currently there is no treatment for Stargardt disease, but one will hopefully be found in the not too distant future.
More information about Stargardt disease may be found in the MD Support Library.
Juvenile Retinoschisis (X-Linked)
Juvenile retinoschisis is diagnosed in childhood and causes progressive loss of central vision and peripheral vision due to retinal degeneration. This dystrophy occurs almost exclusively in males and symptoms do not typically become apparent until after the age of ten.
Vision loss is caused by the splitting of the retina into two layers affecting the macula, the central part of the retina. The fovea, center of the macula, has spoke-like streaks. The spaces created by the separated layers are often filled with blisters and ruptured blood vessels that can leak blood into the vitreous body, and this leads to further vision impairment. The vitreous body degenerates, and may eventually separate from the retina. The entire retina may also separate from underlying tissue layers causing retinal detachment.
The extent of vision loss varies among patients with this disorder. Some people retain useful vision well into adulthood, while others experience a more rapid decline during childhood.
Juvenile retinoschisis is passed through families by the X-linked pattern of inheritance, located on the X chromosome. Females have two X chromosomes, and can carry the disease gene on one of them. Because they have a healthy version of the gene on their other X chromosome, females typically are not affected by X-linked diseases such as this one. Males have only one X-linked chromosome (paired with one Y chromosome) and are therefore genetically susceptible to X-linked diseases. Males affected with an X-linked disease always pass the gene on to their daughters, who then become carriers. Affected males never pass an X-linked disease gene to their sons, because fathers pass the Y chromosome to their sons. Therefore, female carriers have a 50% chance of passing the X-linked disease gene to their daughters, who then become carriers, and a 50% chance of passing the gene to their sons, who are then affected by the disease.
At this time, there is no treatment for juvenile retinoschisis. However, in some cases, surgery can repair retinal detachments.
Individuals with juvenile macular degeneration may benefit from the use of low vision aids and orientation and mobility training. Adaptive training skills, job placement, orientation and mobility training, and income assistance are available through community resources.
Genetic Research
New techniques are becoming available to locate disease-causing genes on each of the twenty-three pairs of chromosomes to locate and study these genes in order to determine their mutations. Retinal degeneration researchers have already found some of these genes that cause these eye diseases, and are continuously searching for others. In medicine, genetic research has the greatest impact so far in testing for retinal degenerations. As more genes are identified, new gene based therapies are being developed.
Genetic Counseling
Questions about a family’s risks for developing a genetic disorder like retinal degeneration are best answered in a genetic counseling session. Genetic counseling can provide specific and practical information about the inheritance of genetic conditions, and such counseling can be provided by an ophthalmologist or family doctor with special training in genetics.
For more information, see “Future Gene Therapy Possible for Inherited MD Patterns.”
The following sites have provided information for this article:
EyeMDLink.com
The Foundation Fighting Blindness
Handbook of Ocular Disease Management
St. Luke’s Cataract & Laser Institute
Review of Ophthalmology
Review of Optometry Online
The Vitreous Retina Macula Consultants of New York
