Norrie disease is a genetic disease characterized by the appearance of pseudoglyoma of the retina of both eyes in the first months of a child’s life and other disorders and malformations. The symptoms of pathology are complete blindness, the presence of retinal hyperplasia and pigment epithelium of the iris, in some cases – progressive mental retardation and hearing impairment. Diagnosis is made using ophthalmological studies, genetic analyses and the study of the patient’s hereditary history. There is no specific treatment for Norrie disease, work with a patient by psychologists and neuropathologists can delay the development or reduce the severity of mental disability.
General information
Norrie disease (oculocerebroacoustic syndrome, congenital bilateral pseudoglyoma of the retina) is a rare hereditary disease that is a congenital retinal dysplasia accompanied by hearing and CNS pathology. It was first described in 1926 by the Danish ophthalmologist G. Norrie and almost at the same time by his compatriot M. Warburg. It is a genetic disease inherited by a recessive, X-linked mechanism. Therefore, Norrie disease is observed only in boys, although there are conflicting data on the presence of visual impairments in female carriers who are heterozygotes. Due to the significant rarity of the disease, its population frequency has not yet been clarified.
Causes
The cause of the disease is a mutation of the NDP gene located on the X chromosome. It encodes a special protein called the Norrie Disease Protein, its functions in the human body have not been thoroughly studied. During the study of laboratory animals, in particular mice, it was found that a similar protein, more than 90% identical to the above factor, controls the differentiation of retinal cells. In addition, it participates in the formation of intercellular connections in the central nervous system. It is possible that this protein plays a similar role in the human body, which is why violations of its structure cause damage to the retina and central nervous system, which is observed in Norrie disease.
The pathogenesis of disorders in this pathology has also not been studied, there are only a few basic hypotheses trying to explain the processes leading to the development of pseudogliomas of the retina, hyperplasia of the ciliated body and the iris. It is assumed that the receptors for angiogenic growth factors in the retinal vessels and other elements of the neuroectoderm are impaired. The variability of such symptoms of Norrie disease as mental retardation and hearing loss is presumably explained by a large number of types of mutations of the NDP gene – more than 30 are known to date. Using the methods of modern genetics, scientists are trying to identify a certain nature of the course of pathology with a specific type or group of mutations, but these studies are hindered due to the rarity of the disease.
Symptoms
Manifestations of the disease can be detected at different times – at the stage of intrauterine development (using echography), immediately after birth, in the first months of a person’s life. Statistically, it is the latter variant of the detection of Norrie disease that is more common – as a rule, parents consult a doctor about bilateral leukocoria in their child. It is caused by the development of retinal dysplasia with the appearance of pseudoglial growths in the form of shapeless masses. If the examination of the fundus is performed before their formation, then there is a folding of the retina of the eye, sometimes its detachment. These manifestations can also be detected when examining the fundus of a newborn with Norrie disease, but their absence is also possible at such an early age. Very rarely, symptoms of the disease are detected in premature infants or with preventive echography – microphthalmos, phthisis of one or both eyeballs are detected, which can be seen with an ultrasound of the eye.
Subsequently, within a few months after the appearance of pseudoglial dysplastic masses, complete blindness develops, in most patients this occurs by the 8th month of life. Norrie disease also leads to the development of cataract and corneal edema – in rare cases, these symptoms appear before leukocoria, so changes in the retina become invisible. The final result of ophthalmic changes is atrophy and phthisis of both eyes. Sometimes pathological processes in the eyes lead to a pronounced pain syndrome and make the child restless – this can serve as an indirect sign of the disease.
Extraocular manifestations of Norrie disease are dementia and hearing impairment of a sensorineural nature. Mental retardation (oligophrenia) cannot be diagnosed in the first months of a child’s life, it is usually detected in the first or second year of life, its degree can progress with age. But it is detected, according to various data, only in 25-50% of patients with Norrie disease, in other cases an acceptable level of mental development is maintained. A similar situation with hearing disorders – hearing loss of varying severity is registered in 35-60% of people with this disease. It occurs much later than other symptoms of Norrie disease – in childhood or adolescence.
Diagnostics
Diagnosis of Norrie disease can be both prenatal and performed after birth by methods of clinical ophthalmology, genetic studies and the study of hereditary history. With prenatal diagnosis at late stages of intrauterine development, echographic methods can reveal microphthalmos, retinal detachment and other disorders of the formation of the visual apparatus. But this is not always possible, since in most cases pronounced ophthalmic symptoms occur after birth. A much more specific method of prenatal diagnosis of Norrie disease will be the detection by a geneticist of mutations of the NDP gene in the material obtained by amniocentesis or biopsy of chorionic villi.
Ophthalmological examination of the fundus (ophthalmoscopy) at various stages of the development of the disease shows the presence of folds and detachment of the fiber, hemorrhages, edema of the optic disc are possible. In the future, these changes are replaced by fibrovascular masses corresponding to pseudoglial dysplasia. During a biopsy of the retina of the eye, glial proliferation is detected, similar processes are detected in the vitreous body. The final ophthalmological symptoms of Norrie disease will be corneal opacity, iris neovascularization and atrophy of the eye.
Genetic diagnosis of the disease is performed by direct sequencing of the NDP gene sequence in order to detect mutations. The object of the study can be both patients with suspected Norrie disease and their closest relatives, especially the mother, since she may be a carrier of a pathological gene. It is the genetic analysis that is the most reliable and unambiguous in determining this disease. Differential diagnosis should be carried out with retinoblastoma, Warburg syndrome, Patau syndrome.
Treatment and prognosis
There is no specific treatment for Norrie disease, only symptomatic therapy is possible. However, she is not able to preserve the vision of patients or at least slow down the progression of pathology. In cases where a pronounced pain syndrome is determined, it is recommended to perform enucleation, or removal of the eye. If mental retardation is detected, timely classes of a child with a psychologist can slow down its development, but a positive result of such treatment is not guaranteed, since the degree of dementia strongly depends on genetic factors. Hearing disorders can be corrected by wearing a hearing aid in cases where the mental retardation of the patient does not reach a severe degree.
In general, the prognosis of Norrie disease is unfavorable – patients lose their sight at an early age and in some cases have severe dementia and hearing impairment. In adolescence and adulthood, attacks of acute psychosis are possible, often serving as a reason for hospitalization in specialized institutions. Prevention of Norrie disease can be carried out by prenatal genetic diagnosis in the early stages of pregnancy. It is especially necessary to perform such a check in cases where parents have been found to have a defective NDP gene or there have been cases of Norrie disease in relatives.Norrie disease is a genetic disease characterized by the appearance of pseudoglyoma of the retina of both eyes in the first months of a child’s life and other disorders and malformations. The symptoms of pathology are complete blindness, the presence of retinal hyperplasia and pigment epithelium of the iris, in some cases – progressive mental retardation and hearing impairment. Diagnosis is made using ophthalmological studies, genetic analyses and the study of the patient’s hereditary history. There is no specific treatment for Norrie disease, work with a patient by psychologists and neuropathologists can delay the development or reduce the severity of mental disability.
