Norrie syndrome is an early childhood, severe eye development disorder in boys. This is characterized by degenerative as well as proliferative changes in the neuroretina and can lead to blindness at a very early age. With few exceptions, Norrie syndrome occurs only in the male sex. An incidence of 1:100,000 is suspected.
What is Norrie syndrome?
Norrie syndrome is a severe disorder of eye development, resulting in congenital blindness. The disease affects almost only boys and men, respectively. In addition to blindness, which can occur very early, about half of the patients also show progressive mental impairments. These include reduced intelligence and behavioral problems. About 30 percent of those affected develop deafness in the second decade of life. Additional problems include retinal detachment, progressive opacities of the lens, vitreous and cornea, atrophy of the iris, and bulbar atrophy. These sequelae usually occur in the first decade after birth.
Causes
The hereditary disease, Norrie syndrome, is caused by a so-called gene mutation of the X- chromosomes. Through an inheritance, there is reduced development of both eyes, which eventually leads to blindness. Normally, this disease affects only men. Women with a mutated gene copy are typically healthy, however, according to statistics, they have a 50 percent risk of passing the disease on to their children.
Symptoms, symptoms and signs
The first symptom visible in Norrie syndrome is usually a whitish-yellow, cloudy pupillary reflex on both sides (leukocoria). Almost all patients suffering from Norrie syndrome are blind from birth. This is caused by retrolental vascularized membranes. This is a partial or complete detachment of the retina from the ocular fundus. From this an undifferentiated growing vascularized tissue has formed. Therefore, the term pseudotumor of the retina (pseudoglioma) is often used. In rare cases, perception of light is preserved for several years. In these affected individuals, it is usually observed that the retina detaches from the fundus of the eye with a delay. As the disease progresses, the entire eyeball usually shrinks (atrophy). Some affected individuals also develop glaucoma and hemorrhages into the retina and vitreous. When the patients are 10 to 20 years old, they usually also develop a progressive hearing loss, which initially affects the high frequencies. Between 20 and 30, they usually have bilateral hearing loss. Half of the patients also show cognitive impairment or behavioral problems. Epileptic seizures have also been described in association with Norrie syndrome. Furthermore, venous insufficiency, particularly in the legs, has been reported by some affected individuals.
Diagnosis and course of the disease
Norrie syndrome requires close examination because some other diseases show a strong resemblance, making it easy to confuse. These include, for example, retinoblastoma, persistent hyperplastic primary vitreous, primary retinal dysplasia, retinopathy of prematurity, Coats disease, osteoporosis pseudoglioma syndrome, X-linked juvenile retinoschisis, and especially familial exudative
vitreoretinopathy. Consequently, genetic testing is the prerequisite to make a clear diagnosis. Due to its already prenatal detection, Norrie syndrome can be diagnosed prenatally. Clinical genetic testing allows for familial risk assessment. Disease-causing mutations can be determined in almost all male cases by direct sequencing. If the suspicion of Norrie syndrome cannot be confirmed by DNA testing, it is useful to analyze other genes that have been associated with similar diseases. Options include testing the whitish pupillary reflex and performing a posterior ophthalmoscopy.
Complications
The most common complication to be expected in Norrie syndrome is complete loss of eyesight. Many affected individuals are born blind, and in other patients it is a progressive process, but usually sight is lost by the age of ten at the latest.To make matters worse, the disease is often not diagnosed until the retina has already completely detached. If the detachment process is detected in time, vision can be maintained in some patients with the help of laser surgery on the eye. Some of the affected individuals develop further complications over time. In particular, affected individuals develop signs of mental retardation. The cognitive abilities of affected children do not develop according to their age. They show difficulties in learning and often also social behavioral problems. In these cases, both drug treatment and psychotherapy are usually necessary. For the families of the affected persons, this is accompanied by a considerable additional care effort. At the latest in the second half of life, the majority of patients show the onset of hearing loss, which can lead to complete loss of hearing. However, this corresponds to the extreme extent of the disease, many patients can be helped permanently with a hearing aid.
When should you go to the doctor?
Norrie syndrome is congenital and is usually detected immediately after birth. Parents of the affected child must see a doctor regularly so that new and unusual symptoms can be clarified and treated. If accidents or falls occur as a result of the existing symptoms, the emergency services must be alerted. During therapy, the patient must continue to be constantly monitored by a physician. Due to the high risk of fractures and other complications, inpatient treatment in a specialized clinic is usually necessary. In addition, the sufferer must be supported by friends and acquaintances who can immediately call the emergency doctor in the event of a medical emergency. Depending on the type and severity of the symptoms, various specialists must be involved in the treatment. Opacities of the cornea as well as cataracts or eye tremors must be treated by an ophthalmologist. Hearing loss must be treated by an ear specialist. If mental disabilities and/or behavioral problems occur, therapeutic measures are necessary. Parents also usually need the support of a psychologist.
Treatment and therapy
To date, there are no known sufficient therapeutic options for a causal cure. In treatment, only the various symptoms can be treated therapeutically, but not the causes. When the initial diagnosis is made, the retina has usually already detached completely and irreversibly. Those affected who have not yet completely lost their vision may be helped with surgery or laser treatment. Similarly, hearing aids and cochlear implants can be used to treat progressive hearing loss. In the case of conspicuous behavioral patterns or cognitive difficulties, it is possible to positively influence this development through psychological counseling and special medication. In general, sufficient care and attention from family, friends or caregivers is required. If this is provided, people suffering from Norrie syndrome can still lead full lives.
Outlook and prognosis
The prognosis of Norrie syndrome is unfavorable. The affected person is mostly male and is born with a genetic defect. The legal requirements of our country prohibit any intervention or alteration in human genetics. As a result, the causative disorder cannot be treated by doctors and medical professionals. Moreover, since the syndrome is associated with loss of vision as well as cognitive impairment, there are difficulties in obtaining adequate treatment. Current medical options do not allow for alleviation of the symptoms so that vision can be restored to a normal level or intelligence can develop in line with the average. Another complicating factor is that some complaints are not detected immediately after birth, but develop during the course of life. These lead to a deterioration of the general quality of life. In addition to behavioral problems, hearing loss is also possible. Possibilities of early intervention are applied, but often do not show a sufficient degree of success. If the diagnosis is made quickly and an individual treatment plan is developed, the best results will be achieved in the further course.Nevertheless, the disease represents a considerable burden for the affected person as well as his or her relatives. Coping with everyday life is not possible throughout life without help and support. Long-term therapies are necessary, which are modified and adapted depending on the development of the symptoms.
Prevention
Genetic testing and counseling have played an important role since the gene locus has been known. It is possible to identify carriers and to avail oneself of prenatal diagnostics. Within a family, congenital blindness may be more common if a genetic defect responsible for it does not occur as a mutation but is inherited from one generation to the next. A human geneticist, if he knows the genetic defect, can determine how high the risk is that one’s own child will be blind at birth. In the best case, however, he can also give the all-clear. During human genetic testing, the chromosomes are examined for changes. If a genetic defect is suspected, further complex examinations can be carried out to check the gene constellations and to estimate the risk of possible inheritance.
Follow-up
Since the malformations caused by Norrie syndrome are not curable, there is no aftercare in the strict sense. Regular checkups with a specialist are indicated so that any new symptoms that arise can be classified. Under certain circumstances, treatment can alleviate the symptoms or help to preserve vision for longer. Depending on the severity of the visual and hearing impairments, those affected are dependent on help in everyday life. If both defective vision and hearing loss occur, they can hardly orient themselves alone and should always be accompanied. However, the home can be adapted for the disabled, so that people with Norrie syndrome can move freely in the home environment. If intelligence impairments or behavioral problems occur, these should be treated separately to the extent possible. In any case, attendance at a special school is recommended, where the special needs of the children can be addressed. There they learn to develop their potential despite the limitations and gain at least partial independence. By applying for a severely handicapped ID card, disadvantages caused by the visual and hearing impairments can be compensated. If an accompanying person is required, he or she receives free admission to many facilities. Tax concessions or, for example, the reduction of the broadcasting fee are also possible with proven severe sensory impairment.
What you can do yourself
Norrie syndrome usually ends in loss of hearing for those affected. If diagnosed early, treatment measures may still be able to save the hearing ability. Therapy can be supported by seeking psychological counseling. Although this cannot alleviate the hearing loss itself, any behavioral problems or cognitive difficulties can be corrected through comprehensive care. Hearing loss can be corrected with hearing aids and cochlear implants. Nevertheless, parents are indicated to support the child and work out further measures to help the child live a relatively symptom-free life. For example, parents can learn sign language or work out certain distress signs with the child. In the long term, those affected by Norrie syndrome need comprehensive medical and therapeutic support, accompanied by the help of relatives and friends. If the child continues to behave in a conspicuous manner and thereby endangers himself or others, a specialized clinic must be consulted. It may also be necessary to change the medication or other measures can be taken to reduce the child’s suffering. Exactly which measures are indicated can be discussed in a comprehensive consultation with the pediatrician in charge.
