Norrie disease
Encyclopedia
Norrie Disease is a genetic disorder
that primarily affects the eye
and almost always leads to blindness
. In addition to the congenital ocular symptoms, some patients suffer from a progressive hearing loss starting mostly in their 2nd decade of life, while another portion may be mentally challenged.
Patients with Norrie Disease may develop cataracts, leukocoria
(a condition where the pupils appear white when light is shone on them), along with other developmental issues in the eye, such as shrinking of the globe and the wasting away of the iris
.
Around 30-50% of them will also have developmental delay/mental retardation
, psychotic-like features, incoordination of movements
or behavioral abnormalities.
Most patients are born with normal hearing; however, the onset of hearing loss is very common in early adolescence. About 15% of the patients are estimated to develop all the features of the disease.
The disease affects almost only male infants at birth or soon after birth, because the disease is inherited X-linked recessive
. Only in very rare cases, females have been diagnosed with Norrie Disease as well. The exact incidence number is unknown; only a few hundred cases have been reported so far. It is a very rare disorder that is not associated with any specific ethnic or racial groups.
The first member of the family to be thoroughly studied was a 12-month-old boy. At the child’s examination at three months, it was noticed that he was normal except for his lens appeared to be opaque and his irises were deteriorating. The area behind his lens was filled with a growing yellowish mass. Five months later, his left eye was removed due to the suspicion of retinoblastoma
, a cancerous tumor
on the retina
. An histologic
examination showed a hemorrhagic necrotic mass in the posterior chamber
, surrounded by undifferentiated (immature, undeveloped) glial tissue. The diagnosis included a pseudotumor of the retina, hyperplasia
of retinal, ciliary, and iris pigment epithelium
, hypoplasia
and necrosis
of the inner layer of the retina, cataract
, and Phthisis bulbi
. This means his eye was removed because the physician suspected a tumor, although it emerged that it was a developmental defect that lead to the malformation of inner parts of the eye. Because the eye was not functional, cells already began to die (necrosis) and the eye globe began to shrink due to its dysfunction (phthisi bulbi). In this Danish family, five of the seven people in these cases developed deafness later in life. Also, in four of the seven, mental capacity was determined low. After Warburg researched literature under various medical categories, she discovered 48 similar cases which she believed were cause by this disease as well. She then suggested this disease be named after another famous Danish ophthalmologist, Gordon Norrie
(1855–1941). Norrie was greatly recognized for his work with the blind and for being a surgeon at the Danish Institute for the Blind for 35 years.
Norrie Disease is a genetic disorder caused by mutations in the NDP
gene
, located on Xp11.4 (GeneID: 4693).
It is inherited in an X-linked recessive
way from usually one of your parents. This means that almost only males are affected. Sons of affected men will not have the mutation, while all of their daughters will be genetic carrier
s of the mutation. They also usually show no clinical symptoms, but will inherit the mutation to 50% of their offspring
. Daughters receiving the mutated gene will also be, like their mother, asymptomatic carriers, but 50% of their sons will express clinical symptoms.
Females are very unlikely to express clinical signs. One possible scenario leading to this (unlikely) case would be if both of their copies of the NDP gene bear mutations, which could be the case in consanguineous families or due to a spontaneous somatic mutation
. Another explanation for affected females could be skewed X-Chromosome inactivation
.
However, throughout history, there have been a few rare cases where females have shown symptoms associated with Norrie Disease such as retinal abnormalities and mild hearing loss.
in NDP
gene causes Norrie disease.
The official name of the gene is “Norrie disease (pseudoglioma)”. The gene’s official symbol is NDP. The normal function of the NDP gene is to produce the instructions for creating a protein
called norrin. For the normal development of the eye and other body systems, norrin is believed to be crucial. Norrin also appears to be crucial in the specialization of the cells of the retina and the establishment of a blood
supply to the inner ear
and the tissues of the retina. The role of norrin in the specialization of retinal cells for their unique sensory is interfered by the mutation of NDP.
This results in an accumulation of immature retinal cells in the back of the eye.
When norrin’s role in the establishment of blood vessels supplying the eye is disrupted, eventually the tissues will break down.
Norrin is not only important in the development of the eye. The mutation of the NDP gene can affect other systems of the body as well. The most severe problems are caused by chromosomal deletions in the region of the NDP gene, causing the prevention of the gene product, or even that of the neighboring MAO
genes. When the mutations simply change a single amino acid
in norrin, the effects are less widespread and severe. However, the location and type of the NDP mutation not necessarily determine the degree of severity of the disease, since highly varying clinical signs have been diagnosed in patients carrying the very same mutation. Therefore, the involvement of other modifying genes is very likely. On the other hand, if certain structurally important amino acids are changed (e.g. the Cysteine
s forming the putative cystine knot
), the clinical outcome has been shown to be more serious.
findings. Norrie Disease is diagnosed when grayish-yellow fibrovascular masses are found behind the eye from birth through three months. Doctors also look for progression of the disease from three months through eight-ten years of age. Some of these progressions include cataracts, iris atrophy
, shallowing of anterior chamber
, and shrinking of the globe. By this point, the vision
is light perception impaired or non-existent.
Molecular genetic testing is used for more than an initial diagnosis. It is used to confirm diagnostic testing, for carrier testing females, prenatal diagnosis, and preimplantion genetic diagnosis. There are three types of clinical molecular genetic testing. In approximately 85% of males, mis-sense and splice mutations of the NDP gene and partial or whole gene deletions are detected using sequence analysis. Deletion/duplication analysis can be used to detect the 15% of mutations that are submicroscopic
deletions. This is also used when testing for carrier females. The last testing used is linkage analysis, which is used when the first two are unavailable. Linkage analysis is also recommended for those families who have more than one member affected by the disease.
, a grayish-yellow pupil
lary reflex that originates from a mass of unorganized tissue behind the lens
. This material, which possibly includes an already detached retina
, may be confused with a tumor and thus is termed pseudoglioma
.
However, an affected baby may have a normally sized eye globe and inconspicuous iris
, anterior chamber
, cornea
and intraocular pressure
.
Over the first few months of life, complete or partial retinal detachment
evolves. From the time they’re a baby through childhood
, the patient may undergo progressive changes in the disease. These progressions include the formation of cataracts, deterioration of the iris
with adhesions forming between the iris
and the lens
or the cornea
, and shallowing of the anterior chamber
which increases intraocular pressure
that can become painful. As the situation worsens, there is corneal opacification, where the cornea
becomes opaque, and band keratopathy. Intraocular pressure is lost and the globe shrinks.
In the last stage of Norrie disease, the globes appear small and sunken in (phthisis bulbi
) and the cornea
appears to be milky .
Norrie disease can also have cognitive and behavioral symptoms. Developmental delay and mental retardation are present in about 30-50% of males who have Norrie disease. Psychotic-like features and poorly characterized behavior abnormalities may also be present. Auditory
symptoms are often common with Norrie disease. Progressive hearing loss starts in early childhood for a majority of males with the disease. Early hearing loss is sensorineural, mild and asymmetric. By adolescence
, high-frequency hearing loss begins to appear. Hearing loss is severe, symmetric, and broad-spectrum by the age of 35. However, studies show that while the hearing loss is deteriorating, the ability to speak well is highly preserved. The slowly progressing hearing loss is more problematic in adjusting to than the congenital blindness for most people with Norrie disease.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
that primarily affects the eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
and almost always leads to blindness
Blindness
Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...
. In addition to the congenital ocular symptoms, some patients suffer from a progressive hearing loss starting mostly in their 2nd decade of life, while another portion may be mentally challenged.
Patients with Norrie Disease may develop cataracts, leukocoria
Leukocoria
Leukocoria is an abnormal white reflection from the retina of the eye. Leukocoria resembles eyeshine, but leukocoria can occur in humans and other animals that lack eyeshine because their retina lacks a tapetum lucidum....
(a condition where the pupils appear white when light is shone on them), along with other developmental issues in the eye, such as shrinking of the globe and the wasting away of the iris
Iris (anatomy)
The iris is a thin, circular structure in the eye, responsible for controlling the diameter and size of the pupils and thus the amount of light reaching the retina. "Eye color" is the color of the iris, which can be green, blue, or brown. In some cases it can be hazel , grey, violet, or even pink...
.
Around 30-50% of them will also have developmental delay/mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
, psychotic-like features, incoordination of movements
Spinocerebellar ataxia
Spinocerebellar ataxia is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a disease in its own right.-Classification:...
or behavioral abnormalities.
Most patients are born with normal hearing; however, the onset of hearing loss is very common in early adolescence. About 15% of the patients are estimated to develop all the features of the disease.
The disease affects almost only male infants at birth or soon after birth, because the disease is inherited X-linked recessive
X-linked recessive
X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be expressed in males and in females who are homozygous for the gene mutation X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on...
. Only in very rare cases, females have been diagnosed with Norrie Disease as well. The exact incidence number is unknown; only a few hundred cases have been reported so far. It is a very rare disorder that is not associated with any specific ethnic or racial groups.
History
In 1961, a Danish ophthalmologist named Mette Warburg reported that a Danish family showed seven different cases of a hereditary degenerative disease throughout seven generations.The first member of the family to be thoroughly studied was a 12-month-old boy. At the child’s examination at three months, it was noticed that he was normal except for his lens appeared to be opaque and his irises were deteriorating. The area behind his lens was filled with a growing yellowish mass. Five months later, his left eye was removed due to the suspicion of retinoblastoma
Retinoblastoma
Retinoblastoma is a rapidly developing cancer that develops in the cells of retina, the light-detecting tissue of the eye. In the developed world, Rb has one of the best cure rates of all childhood cancers , with more than nine out of every ten sufferers surviving into...
, a cancerous tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
on the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
. An histologic
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
examination showed a hemorrhagic necrotic mass in the posterior chamber
Posterior chamber
The posterior chamber should not be confused with vitreous chamber. The posterior chamber is a narrow chink behind the peripheral part of the iris of the lens, and in front of the suspensory ligament of the lens and the ciliary processes. The Posterior Chamber consists of small space directly...
, surrounded by undifferentiated (immature, undeveloped) glial tissue. The diagnosis included a pseudotumor of the retina, hyperplasia
Hyperplasia
Hyperplasia means increase in number of cells/proliferation of cells. It may result in the gross enlargement of an organ and the term is sometimes mixed with benign neoplasia/ benign tumor....
of retinal, ciliary, and iris pigment epithelium
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
, hypoplasia
Hypoplasia
Hypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia...
and necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
of the inner layer of the retina, cataract
Cataract
A cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...
, and Phthisis bulbi
Phthisis bulbi
Phthisis bulbi is a shrunken, non-functional eye that results from severe ocular disease, inflammation, or injury ....
. This means his eye was removed because the physician suspected a tumor, although it emerged that it was a developmental defect that lead to the malformation of inner parts of the eye. Because the eye was not functional, cells already began to die (necrosis) and the eye globe began to shrink due to its dysfunction (phthisi bulbi). In this Danish family, five of the seven people in these cases developed deafness later in life. Also, in four of the seven, mental capacity was determined low. After Warburg researched literature under various medical categories, she discovered 48 similar cases which she believed were cause by this disease as well. She then suggested this disease be named after another famous Danish ophthalmologist, Gordon Norrie
Gordon Norrie
Gordon Norrie was a Danish surgeon and ophthalmologist of Scottish parentage who was born in Helsingør . He was married to Charlotte Norrie, née Harbou , who was a pioneer of modern nursing....
(1855–1941). Norrie was greatly recognized for his work with the blind and for being a surgeon at the Danish Institute for the Blind for 35 years.
Causes
NDP (gene)
Norrin, also known as Norrie disease protein or X-linked exudative vitreoretinopathy 2 protein is a protein that in humans is encoded by the NDP gene...
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
, located on Xp11.4 (GeneID: 4693).
It is inherited in an X-linked recessive
X-linked recessive
X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be expressed in males and in females who are homozygous for the gene mutation X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on...
way from usually one of your parents. This means that almost only males are affected. Sons of affected men will not have the mutation, while all of their daughters will be genetic carrier
Genetic carrier
A genetic carrier , is a person or other organism that has inherited a genetic trait or mutation, but who does not display that trait or show symptoms of the disease. They are, however, able to pass the gene onto their offspring, who may then express the gene...
s of the mutation. They also usually show no clinical symptoms, but will inherit the mutation to 50% of their offspring
Offspring
In biology, offspring is the product of reproduction, of a new organism produced by one or more parents.Collective offspring may be known as a brood or progeny in a more general way...
. Daughters receiving the mutated gene will also be, like their mother, asymptomatic carriers, but 50% of their sons will express clinical symptoms.
Females are very unlikely to express clinical signs. One possible scenario leading to this (unlikely) case would be if both of their copies of the NDP gene bear mutations, which could be the case in consanguineous families or due to a spontaneous somatic mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
. Another explanation for affected females could be skewed X-Chromosome inactivation
X-inactivation
X-inactivation is a process by which one of the two copies of the X chromosome present in female mammals is inactivated. The inactive X chromosome is silenced by packaging into transcriptionally inactive heterochromatin...
.
However, throughout history, there have been a few rare cases where females have shown symptoms associated with Norrie Disease such as retinal abnormalities and mild hearing loss.
The NDP Gene
A mutationMutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
in NDP
NDP (gene)
Norrin, also known as Norrie disease protein or X-linked exudative vitreoretinopathy 2 protein is a protein that in humans is encoded by the NDP gene...
gene causes Norrie disease.
The official name of the gene is “Norrie disease (pseudoglioma)”. The gene’s official symbol is NDP. The normal function of the NDP gene is to produce the instructions for creating a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
called norrin. For the normal development of the eye and other body systems, norrin is believed to be crucial. Norrin also appears to be crucial in the specialization of the cells of the retina and the establishment of a blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
supply to the inner ear
Inner ear
The inner ear is the innermost part of the vertebrate ear. In mammals, it consists of the bony labyrinth, a hollow cavity in the temporal bone of the skull with a system of passages comprising two main functional parts:...
and the tissues of the retina. The role of norrin in the specialization of retinal cells for their unique sensory is interfered by the mutation of NDP.
This results in an accumulation of immature retinal cells in the back of the eye.
When norrin’s role in the establishment of blood vessels supplying the eye is disrupted, eventually the tissues will break down.
Norrin is not only important in the development of the eye. The mutation of the NDP gene can affect other systems of the body as well. The most severe problems are caused by chromosomal deletions in the region of the NDP gene, causing the prevention of the gene product, or even that of the neighboring MAO
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...
genes. When the mutations simply change a single amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
in norrin, the effects are less widespread and severe. However, the location and type of the NDP mutation not necessarily determine the degree of severity of the disease, since highly varying clinical signs have been diagnosed in patients carrying the very same mutation. Therefore, the involvement of other modifying genes is very likely. On the other hand, if certain structurally important amino acids are changed (e.g. the Cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
s forming the putative cystine knot
Cystine knot
A cystine knot is a protein structural motif where two disulfide bridges are formed. The sections of polypeptide that occur between them then form a loop through which a third disulfide bond passes, forming a rotaxane substructure...
), the clinical outcome has been shown to be more serious.
Diagnosis
As of right now, Norrie Disease and other NDP related diseases are diagnosed with the combination of clinical findings and molecular genetic testing. Molecular genetic testing identifies the mutations that cause the disease in about 85% of affected males. Clinical diagnoses rely on ocularHuman eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
findings. Norrie Disease is diagnosed when grayish-yellow fibrovascular masses are found behind the eye from birth through three months. Doctors also look for progression of the disease from three months through eight-ten years of age. Some of these progressions include cataracts, iris atrophy
Atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
, shallowing of anterior chamber
Anterior chamber
The anterior chamber is the fluid-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. Aqueous humor is the fluid that fills the anterior chamber. Hyphema and glaucoma are two main pathologies in this area. In hyphema, blood fills the anterior chamber...
, and shrinking of the globe. By this point, the vision
Visual perception
Visual perception is the ability to interpret information and surroundings from the effects of visible light reaching the eye. The resulting perception is also known as eyesight, sight, or vision...
is light perception impaired or non-existent.
Molecular genetic testing is used for more than an initial diagnosis. It is used to confirm diagnostic testing, for carrier testing females, prenatal diagnosis, and preimplantion genetic diagnosis. There are three types of clinical molecular genetic testing. In approximately 85% of males, mis-sense and splice mutations of the NDP gene and partial or whole gene deletions are detected using sequence analysis. Deletion/duplication analysis can be used to detect the 15% of mutations that are submicroscopic
Submicroscopic
Submicroscopic is an English adjective used to describe particles of matter that cannot be seen under the most powerful optical microscope available. Atoms are examples of such submicroscopic particles....
deletions. This is also used when testing for carrier females. The last testing used is linkage analysis, which is used when the first two are unavailable. Linkage analysis is also recommended for those families who have more than one member affected by the disease.
Symptoms
The most prominent symptoms of Norrie Disease are ocular. The first visible finding is LeukocoriaLeukocoria
Leukocoria is an abnormal white reflection from the retina of the eye. Leukocoria resembles eyeshine, but leukocoria can occur in humans and other animals that lack eyeshine because their retina lacks a tapetum lucidum....
, a grayish-yellow pupil
Pupil
The pupil is a hole located in the center of the iris of the eye that allows light to enter the retina. It appears black because most of the light entering the pupil is absorbed by the tissues inside the eye. In humans the pupil is round, but other species, such as some cats, have slit pupils. In...
lary reflex that originates from a mass of unorganized tissue behind the lens
Lens (anatomy)
The crystalline lens is a transparent, biconvex structure in the eye that, along with the cornea, helps to refract light to be focused on the retina. The lens, by changing shape, functions to change the focal distance of the eye so that it can focus on objects at various distances, thus allowing a...
. This material, which possibly includes an already detached retina
Retinal detachment
Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blindness. It is a medical emergency.The retina is a...
, may be confused with a tumor and thus is termed pseudoglioma
Glioma
A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...
.
However, an affected baby may have a normally sized eye globe and inconspicuous iris
Iris (anatomy)
The iris is a thin, circular structure in the eye, responsible for controlling the diameter and size of the pupils and thus the amount of light reaching the retina. "Eye color" is the color of the iris, which can be green, blue, or brown. In some cases it can be hazel , grey, violet, or even pink...
, anterior chamber
Anterior chamber
The anterior chamber is the fluid-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. Aqueous humor is the fluid that fills the anterior chamber. Hyphema and glaucoma are two main pathologies in this area. In hyphema, blood fills the anterior chamber...
, cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
and intraocular pressure
Intraocular pressure
Intraocular pressure is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk from glaucoma...
.
Over the first few months of life, complete or partial retinal detachment
Retinal detachment
Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blindness. It is a medical emergency.The retina is a...
evolves. From the time they’re a baby through childhood
Childhood
Childhood is the age span ranging from birth to adolescence. In developmental psychology, childhood is divided up into the developmental stages of toddlerhood , early childhood , middle childhood , and adolescence .- Age ranges of childhood :The term childhood is non-specific and can imply a...
, the patient may undergo progressive changes in the disease. These progressions include the formation of cataracts, deterioration of the iris
Iris (anatomy)
The iris is a thin, circular structure in the eye, responsible for controlling the diameter and size of the pupils and thus the amount of light reaching the retina. "Eye color" is the color of the iris, which can be green, blue, or brown. In some cases it can be hazel , grey, violet, or even pink...
with adhesions forming between the iris
Iris (anatomy)
The iris is a thin, circular structure in the eye, responsible for controlling the diameter and size of the pupils and thus the amount of light reaching the retina. "Eye color" is the color of the iris, which can be green, blue, or brown. In some cases it can be hazel , grey, violet, or even pink...
and the lens
Lens (anatomy)
The crystalline lens is a transparent, biconvex structure in the eye that, along with the cornea, helps to refract light to be focused on the retina. The lens, by changing shape, functions to change the focal distance of the eye so that it can focus on objects at various distances, thus allowing a...
or the cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
, and shallowing of the anterior chamber
Anterior chamber
The anterior chamber is the fluid-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. Aqueous humor is the fluid that fills the anterior chamber. Hyphema and glaucoma are two main pathologies in this area. In hyphema, blood fills the anterior chamber...
which increases intraocular pressure
Intraocular pressure
Intraocular pressure is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk from glaucoma...
that can become painful. As the situation worsens, there is corneal opacification, where the cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
becomes opaque, and band keratopathy. Intraocular pressure is lost and the globe shrinks.
In the last stage of Norrie disease, the globes appear small and sunken in (phthisis bulbi
Phthisis bulbi
Phthisis bulbi is a shrunken, non-functional eye that results from severe ocular disease, inflammation, or injury ....
) and the cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
appears to be milky .
Norrie disease can also have cognitive and behavioral symptoms. Developmental delay and mental retardation are present in about 30-50% of males who have Norrie disease. Psychotic-like features and poorly characterized behavior abnormalities may also be present. Auditory
Auditory system
The auditory system is the sensory system for the sense of hearing.- Outer ear :The folds of cartilage surrounding the ear canal are called the pinna...
symptoms are often common with Norrie disease. Progressive hearing loss starts in early childhood for a majority of males with the disease. Early hearing loss is sensorineural, mild and asymmetric. By adolescence
Adolescence
Adolescence is a transitional stage of physical and mental human development generally occurring between puberty and legal adulthood , but largely characterized as beginning and ending with the teenage stage...
, high-frequency hearing loss begins to appear. Hearing loss is severe, symmetric, and broad-spectrum by the age of 35. However, studies show that while the hearing loss is deteriorating, the ability to speak well is highly preserved. The slowly progressing hearing loss is more problematic in adjusting to than the congenital blindness for most people with Norrie disease.