Hearing Loss/RP Conditions
RP affects the sensory cells in the retina, which is the layer lining the inside of the eye. The retina itself is made up of several layers of interconnecting cells, two of which are called rods and cones. These cells gradually deteriorate and die in RP and many other so-called retinal dystrophies. The 150 million rods in each eye control night vision so that people can see in dim light. Rods are spread throughout the retina except in the fovea, which is the spot in the center back directly behind the pupil. The fovea contains only cones which control day vision and are important for seeing fine details and color. Surrounding the fovea is the macula which is rich in cones, but cones are also scattered throughout the rest of the retina. About 7 million cones are present in each retina. By the time the cones deteriorate doctors can see distinctive changes when they look at the retina. These include pigment dispersion, which means that some parts appear lighter than others, followed by "bone spicules" which are little jagged spots. The blood vessels become narrow or "attenuated" and the optic disc (nerve) develops a pale and waxy yellow appearance. All of these changes get worse as the disease progresses.
Symptoms of RP
In RP, rods deteriorate first, then cones. This means night blindness occurs first, sometimes followed by blind spots, and then slowly progressive tunnel vision during the day. When night blindness is present early in life, infants may not be able to reach for a bottle in the dark. In some cases, toilet training is delayed because young children may be afraid to go to the bathroom unless night-lights are on. When leaving the car at night to go into the house, they may have to hold on to an adult's hand or follow a railing. Later at camp, they may not be able to find the way to the latrine. In residential school dormitories, they may have problems going down the darkened halls or recognizing friends waving to them. Seeing people signing in a dark room or theater becomes difficult or impossible.
When cones begin to die, blind spots (called scotomas) can develop, even in well-lighted conditions. These are recognized during the day several years after night vision problems are noted. At first, the children do not notice anything wrong because the blind spots are in the peripheral (side) vision. If something seems to be missing, individuals with RP usually move their eyes (called scanning) and then the image appears again because they are using the healthy part of the retina. Over several years the blind spots get bigger and more develop until a ring-shaped blind spot is present. At this stage a person can see at the extreme periphery (out toward the shoulder) but nothing between the outer rim of the glasses to the middle. Excellent vision, even 20/20 vision, may remain in the center. A person is declared "legally blind" when only 20 degrees of central vision remain even if some vision is still present way out to the sides. Even at this stage many people do not recognize how much they do not see because they have learned how to scan so rapidly. Nevertheless, they may miss curbs, stairs, or other objects in front of their feet because they have a lower visual field defect. At the table they may reach for something they see clearly but knock over something else in the path which they have not seen. They may bump into open doors, not seeing the narrow edge of the door, or lifting their heads at the kitchen counter, bang their heads on an open cupboard door. By this time bright lights become glaring and rapid changes in light (like going outside) may be dazzling. It takes longer to adapt to new lighting conditions.
Central vision loss may occur much later, though some people may retain 5-10 degrees of good vision into old age. Three things may affect central vision: (1) the cone cells in the fovea may die, though this usually occurs late in life; (2) the macula may become swollen (called cystoid macular edema). This condition can be treated, at least for a while, with medication which makes the swelling go down; and, (3) cataracts may develop in the lens, which sits behind the pupil (black hole in the front of the eye) and focuses the image on the retina. Cataracts occur at about 20-40 years. Since they sit right in the line of sight, they may blur the central vision. Fortunately, cataract operations are becoming increasingly safe and effective.
The symptoms of retinal disease follow this pattern in Usher syndrome but may be somewhat different in other conditions discussed later. In all cases, both rods and cones deteriorate, but the timing may be different.
Hearing Loss in Usher Syndrome
The hearing loss is profound in Type 1. Many people with this type of Usher syndrome say they get little or no benefit from hearing aids. In general, young children who have had cochlear implants do well. However, the success rate of cochlear implants has not been studied specific to each genetic type. While there is no reason to expect differences, it has not been scientifically established that all Usher I types respons equally to cochlear implants. The majority of older people with Usher I use sign language as their primary mode of communication and are culturally deaf.
In Type II children are born hard-of-hearing and able to detect low tones better than high tones. Only a small amount of additional loss (about 10 dB) occurs over several decades in adulthood. Even within a family, however, there may be some difference in severity from person to person. With hearing aids they do well in regular classrooms, usually with preferential seating in the front of the class and sometimes separate classes. These children most commonly use oral speech and language and are culturally hearing though a few have moderate to profound hearing loss and have gone to schools for the deaf. When vision deteriorates, they lose the ability to read speech from the lips. Since the hearing aid does not fully correct the hearing loss, they may become functionally deaf-blind particularly in noisy dark environments such as restaurants or bars in the evening, at dances, or other social events. They may then choose to use FM systems, avoid such environments, or learn sign language.
Type III has a hearing loss that gets steadily worse over the years so hard-of-hearing teens become deaf in mid to late adulthood. Usher Type III is particularly common in Finland but is also seen in the rest of Europe and the United States in about 5 - 10 percent of all Usher cases.
Balance in Usher Syndrome
Most individuals with Type I tested to date in the balance laboratory have absent vestibular function. This means that the semicircular canals of the inner ear, which let a person know what position the head is in, have not worked since birth. The consequence of vestibular dysfunction is that babies have a hard time learning how to crawl and walk. They may prefer to roll rather than get up on all fours, or they may have a "five-point" crawl with their heads down on the ground. Walking is delayed to 15-18 months or even later. Children are considered clumsy, at least until they establish good control of their muscles and joints. Physical education teachers can often pick out the children with balance problems if they cannot turn quickly, walk on a balance beam, etc. On the other hand, they love twirling and merry-go-rounds because they do not get dizzy. Once children have developed good muscle control, they have no problem walking or running, as long as they can see or they know where they are going. When they lose vision, they become unsure of themselves again and are less steady on their feet. A few families have reported that their children do not have balance problems but are profoundly deaf and have RP. Some of these cases have subsequently been shown to have Usher Id and Usher Type III.
Gene Studies in Usher Syndrome
All types of Usher syndrome are caused by autosomal recessive genes. This means that each parent has one normal and one Usher gene, and each gives the affected child the Usher gene. The child then has no normal gene at that locus but two Usher genes. Table 1 shows that 7 separate genes have been located for Type I. Two of these genes are on chromosome #11, one on #14, one on #12, and two on #10. Most people have the Usher gene on the long arm of chromosome #11. Those individuals of Acadian heritage, most of whom live in Louisiana, have the gene on the short arm of #11. The first of the genes discovered was on the long arm of #14 and was described in a small region of France. So far, most people with Type II have a deficient gene on the long arm of chromosome #1. A few families with typical Type II symptoms have a gene on chromosome 3 or 5. The gene for Type III has been identified and is under study here, in Finland and Israel. What all this means is that there is more than one underlying biochemical cause for combined hearing loss and RP. Even when people appear to have the same clinical subtype, the genes causing the condition may be different. This is much like having a measles-like rash which can be caused by many different viruses including those which cause regular measles and German measles.
Other Hearing Loss/RP Conditions
There are a number of conditions which may be confused with Usher syndrome. Rubella (German measles) used to be one of the most commonly suspected conditions. Because the pigment disperses leaving light and dark spots, the retina is said to have a "salt and pepper" appearance. Sometimes this pattern can be seen in early RP and the eye doctor can misinterpret the condition as Rubella. Since Rubella is much less common now than in the 1960s and early 1970s, the diagnosis of Usher syndrome should be considered in cases with salt and pepper pigmentation patterns. Other syndromes have eye findings or hearing loss patterns which are different from those in Usher syndrome as well as abnormalities of other body parts.
by William J Kimberling
originally prepared by
Sandra L.H. Davenport, M.D.
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