Rare Conditions

• Best’s Disease
• Cone-Rod Retinal Dystrophy
• Gyrate Atrophy
• Oguchi Disease
• Juvenile Retinoschisis
• Other Conditions

Best's Disease

What is Best’s Disease?

Best’s disease, also known as Vitelliform Macular Dystrophy, is an inherited form of macular degeneration characterized by a loss of central vision.

What are the symptoms?

Best’s disease affects the macula, the central part of the retina responsible for fine visual detail and colour perception. In the initial stages, a bright yellow cyst forms under the retinal pigment epithelium (RPE) beneath the macula. Despite the presence of the cyst, visual acuity may remain normal or near normal (between 20/30 and 20/50) for many years. Peripheral (side) vision usually remains unaffected.

In many individuals with Best’s disease, the cyst eventually ruptures. Fluid and yellow deposits from the ruptured cyst spread throughout the macula. Once the cyst ruptures, the macula and the underlying RPE begin to atrophy causing further vision loss.

When is it diagnosed?

It is usually diagnosed during childhood or adolescence.

How quickly does it progress?

Central vision tends to deteriorate to about 20/100 late in life. However, Best’s disease does not always affect both eyes equally. Many individuals retain useful central vision in one eye with a visual acuity of about 20/40 in the lesser-affected eye.

In some cases, Best’s disease does not progress far enough to cause significant central vision loss. However, retinal specialists can still detect the disease using sophisticated diagnostic tests that measure the function of the RPE and the retina. Individuals with Best’s disease are also often farsighted. Farsightedness can be corrected with glasses.

How is it transmitted?

Best’s disease is genetically passed through families by the autosomal dominant pattern of inheritance. In this pattern of inheritance, an affected person has one Best’s disease gene paired with one normal gene. When the affected person has children with an unaffected partner, there is a 50 percent chance that the affected parent will pass the disease-causing gene to each child. The unaffected partner will only pass normal genes. A child who does not have the Best’s disease gene will not have the disease and cannot then pass the disease to his or her children.

Can it be treated?

Currently, there is no treatment for Best’s disease. Ongoing scientific research is directed at understanding the cause of Best’s disease. In 1998, researchers identified mutations in a gene causing Best’s disease. Scientists are now studying this gene to determine its function in the retina. This information will greatly enhance efforts to develop treatments for Best’s disease.

Cone-Rod Retinal Dystrophy

What is Cone-Rod Retinal Dystrophy?

Cone-rod retinal dystrophy (CRD) characteristically leads to early impairment of vision.

What are the symptoms?

An initial loss of colour vision and of visual acuity is followed by nyctalopia (night blindness) and loss of peripheral visual fields. In extreme cases, these progressive symptoms are accompanied by widespread, advancing retinal pigmentation and chorioretinal atrophy of the central and peripheral retina.

The onset of decreased central vision with concurrent progressive constriction of peripheral visual fields occurs prior to age 10. Unlike other cone dystrophies, there is an inexorable progression to no light perception.

Evans et al. (1995) reported on the clinical features of 34 affected members in 4 generations. Loss of visual acuity occurred in the first decade of life, onset of night blindness occurred after 20 years of age, and little visual function remained after the age of 50 years. Central and, later, peripheral retinal fundus changes were associated with central scotoma, pseudoaltitudinal field defects, and finally, global loss of function. Psychophysical and electrophysiologic testing before the age of 26 years showed more marked loss of cone than of rod function.

When is it transmitted?

Typically, Cone-Rod Retinal Dystrophy is diagnosed following a loss of visual acuity and progressive constriction of peripheral vision before the age of 10.

Gyrate Atrophy

What is Gyrate Atrophy?

People suffering from gyrate atrophy of the choroid (the thin coating of the eye) and retina face a progressive loss of vision, with total blindness usually occurring between the ages of 40 and 60.

When is it transmitted?

The gene whose mutation causes gyrate atrophy is found on chromosome 10, and encodes an enzyme called ornithine ketoacid aminotransferase (OAT). Different inherited mutations in OAT cause differences in the severity of symptoms of the disease. OAT converts the amino acid ornithine from the urea cycle ultimately into glutamate. In gyrate atrophy, where OAT function is affected, there is an increase in plasma levels of ornithine.

Can it be treated?

It is already known that reduction of the amino acid arginine in the diet has a beneficial effect on most patients. Current lines of research into the disease include:
investigating how variant mutations of the alleles (versions of the gene inherited) interact in order to cause the differing symptoms of the disease and
work on mouse models of the disease is furthering our understanding, which is hoped will lead to a true cure.

Oguchi Disease

What is Oguchi Disease?

The characteristics are congenital, static hemeralopia and diffuse yellow or grey coloration of the fundus. After 2 or 3 hours in total darkness, the normal colour of the fundus returns. The condition is more frequent in Japanese.

What are the symptoms?

Typically, an individual with Oguchi Disease will have stationary night blindness, associated with fundus discolouration and abnormally slow dark adaptation.

When is it transmitted?

Researchers have referred to Oguchi disease as a rare autosomal recessive form of congenital stationary night blindness, associated with fundus discolouration and abnormally slow dark adaptation. Armed with this information, it is suggested that a candidate gene for Oguchi disease is an encoding S antigen, also known as arrestin. This gene encodes a 48-kD protein that may be involved in the recovery phase of light transduction. The SAG gene had been previously been mapped to 2q37.1 by fluorescence in situ hybridization. Because the arrestin gene maps to the same region of 2q as Oguchi disease and because it encodes a rod photoreceptor implicated in the recovery phase of light transduction, SAG was a candidate gene for the site of the mutation in this disorder.

Juvenile Retinoschisis

What is Juvenile Retinoschisis?

Juvenile Retinoschisis is an inherited disease diagnosed in childhood that causes progressive loss of central and peripheral (side) vision due to degeneration of the retina.

What are the symptoms?

Juvenile Retinoschisis, also known as X-linked Retinoschisis, occurs almost exclusively in males. Although the condition begins at birth, symptoms do not typically become apparent until after the age of 10. About half of all patients diagnosed with Juvenile Retinoschisis first notice a decline in vision. Other early symptoms of the disease include an inability of both eyes to focus on an object (strabismus) and roving, involuntary eye movements (nystagmus).

Vision loss associated with Juvenile Retinoschisis is caused by the splitting of the retina into two layers. This retinal splitting most notably affects the macula, the central portion of the retina responsible for fine visual detail and color perception. On examination, the fovea (the centre 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 (the transparent, colourless mass of jelly-like material filling the centre of the eye). The presence of blood in the vitreous body causes further visual impairment. The vitreous body degenerates and may eventually separate from the retina. The entire retina may also separate from underlying tissue layers causing retinal detachments. The extent and rate of vision loss vary greatly among patients with Juvenile Retinoschisis. Central vision is almost always affected. Peripheral (side) vision loss occurs in about half of all cases. Some patients retain useful vision well into adulthood, while others experience a rapid decline during childhood.

How is it transmitted?

Juvenile Retinoschisis is genetically passed through families by the X-linked pattern of inheritance. In this type of inheritance, the gene for the disease is located on the X chromosome. Females have two X chromosomes and can carry the disease gene on one of their X chromosomes. 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 juvenile retinoschisis. Sometimes, however, when carrier females are examined, the retina shows minor signs of the disease.

Males have only one X chromosome (paired with one Y chromosome) and are therefore genetically susceptible to X-linked diseases. Males cannot be carriers of X-linked diseases. Males affected with an X-linked disease always pass the gene on the X chromosome 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. Female carriers have a 50 percent chance (or 1 chance in 2) of passing the X-linked disease gene to their daughters, who become carriers, and a 50 percent chance of passing the gene to their sons, who are then affected by the disease.

Can it be treated?

At this time, there is no treatment for Juvenile Retinoschisis. However, in some cases, surgery can repair retinal detachments. Ongoing scientific research is directed at identifying the gene that causes Juvenile Retinoschisis as the first step in developing means of prevention and treatment.

Other Conditions

Bassen-Kornzweig Disease

Bassen-Kornzweig disease, also known as abetalipoproteinemia, is characterized by retinal degeneration, neuromuscular disability and dietary fat intolerance. It is sometimes confused with Refsum Disease.

Blue Cone Monochromatism Disease

Blue cone monochromatism is characterized by poor central vision and colour discrimination, infantile nystagmus, and nearly normal retinal appearance. The psychophysiologic functions of both rods and blue cones are preserved. The frequency of achromatopsia is said to be approximately 1 in 100,000 persons. This disorder was previously interpreted as total colour-blindness.

Dominant Drusen

Dominant Drusen are caused by the accumulation of drusen, yellow-white deposits, in the macular area. Drusen deposits usually appear in the first three decades of life, and become larger as a person ages. Decreased vision may not be noticed until the fourth decade, with vision varying between 20/30 and 20/80. If the drusen causes other complications in the retina, vision may decrease to 20/200.

Goldman-Favre Vitreoretinal Dystrophy

Or Enhanced S-cone Syndrome. It is sometimes confused with Juvenile Retinoschisis. Expert medical consultation can distinguish between these disorders.

Kearns-Sayre Syndrome

Kearns-Sayre syndrome involves retinal degeneration, ptosis (drooping of upper eyelid), deafness, muscular dystrophy, and cardiac abnormalities. It is sometimes confused with Refsum Disease. Expert medical consultation can distinguish between these disorders.

Laurence-Moon Syndrome

Often confused with Bardet-Biedl Syndrome. Individuals with Laurence-Moon syndrome almost always experience neurologic problems but rarely polydactyly. Polydactyly is a defining feature of Bardet-Biedl syndrome, while neurologic problems almost never occur. Laurence-Moon syndrome is extremely rare; only a few cases have been documented. Because of the similarity of these syndromes, Bardet-Biedl syndrome is often referred to as Laurence-Moon/Bardet-Biedl syndrome or Laurence-Moon/Biedl syndrome.

Peripapillary (pericentral) Choroidal Dystrophy

Peripapillary (pericentral) Choroidal Dystrophy is a condition which causes wasting of the blood vessels that surround the optic nerve. Patients first notice symptoms in the late adult years, when the macula is affected.

Pigment Pattern Dystrophy

Pigment Pattern Dystrophy describes a group of disorders that includes Butterfly-shaped Pigment Dystrophy of the fovea, North Carolina Macular Dystrophy, Macro Reticular (Spider) Dystrophy and Sjogren Reticular Pigment Epithelium Dystrophy. The macular changes in these patients can occur at any age, but usually first appear in childhood. Many patients do not experience symptoms and may have visual acuities in the 6/6 to 6/24 range. Some of the genes have gene identified for these disorders and are located on chromosome 6.

Sorsby Macular Dystrophy

Sorsby Macular Dystrophy is a rare disorder in which new blood vessels grow under the fovea, resulting in fluid build-up in the macular, haemorrhage, and general wasting of other layers of tissue in the eye. Usually symptoms do not appear until after the age of 40. Drusen may also be present. People with this disorder may experience a rapid decrease in vision. The gene for this disorder has been identified as the TIMP3 gene, which is located on the long arm of Chromosome 22.

Stickler’s Syndrome

Sometimes confused with Juvenile Retinoschisis. Symptoms may include joint pain, sensorineural hearing loss and retinal detachment. Expert medical consultation can distinguish between these disorders.

Wagner's Vitreoretinal Dystrophy

Wagner syndrome is a very rare hereditary vitreo-retinal disease. It is one of the connctive tissue disorders affecting the collagen.

The main feature is an "empty" vitreaous that lacks the normal structure. Missing or weak vasculature in the peripheral retina Makes the retina prone to tear or getting detached. Dinished visual acuity at night is also a problem as is the early onset of cataract (from the age of 30) and choroidal atrophy. A lot of people are moderate (> -2) to highly (> -6) myopic. Wagner syndrome is ocular only.

The genetic cause for Wagner syndrome has been found in 2005. The gene reponsible for this disorder is the Versican gene (5q13.4). About 20 families with Wagner syndrome have been found in Switzerland, the Netherlands, France, the UK, the USA and Japan. For more information see: www.wagnersyndrome.eu