Rare Endocrinology News

Disease Profile

Norrie disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

H35.5

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

rnn-xlinkedrecessive.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Atrophia bulborum hereditaria; Pseudoglioma; Episkopi blindness;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Eye diseases;

Summary

Norrie disease is an inherited eye disorder that leads to blindness in male infants at birth or soon after birth.[1][2] Additional symptoms may occur in some cases, although this varies even among individuals in the same family.[2] Most affected individuals develop sensorineural hearing loss and many exhibit cognitive abnormalities such as developmental delays, behavioral issues, or psychotic-like features.[2][3] Norrie disease is caused by mutations in the NDP gene. It is inherited in an X-linked recessive pattern.[1][2] Treatment is directed toward the specific symptoms present in each individual. The coordinated efforts of a team of specialists, including pediatricians, ophthalmologists, and audiologists may be needed. Early intervention and special education services are important to ensure that children with Norrie disease reach their full potential.[2]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal chorioretinal morphology
0000532
Abnormal retinal vascular morphology
Abnormality of retina blood vessels
0008046
Anterior chamber synechiae
0007833
Blindness
0000618
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Deeply set eye
Deep set eye
Deep-set eyes
Sunken eye

[ more ]

0000490
Hypoplasia of the iris
Underdeveloped iris
0007676
Hypotelorism
Abnormally close eyes
Closely spaced eyes

[ more ]

0000601
Macrotia
Large ears
0000400
Microphthalmia
Abnormally small eyeball
0000568
Narrow nasal bridge
Narrow bridge of nose
Nasal Bridge, Narrow
Nasal bridge, thin

[ more ]

0000446
Neoplasm of the eye
Eye tumor
0100012
Sclerocornea
Hardening of skin and connective tissue
0000647
Vascular neoplasm
Blood vessel tumor
0100742
30%-79% of people have these symptoms
Abnormal cochlea morphology
0000375
Anxiety
Excessive, persistent worry and fear
0000739
Aplasia/Hypoplasia of the lens
Absent/small lens
Absent/underdeveloped lens

[ more ]

0008063
Erectile dysfunction
Abnormal erection
Erectile abnormalities

[ more ]

0100639
Intellectual disability, progressive
Mental retardation, progressive
Progressive mental retardation

[ more ]

0006887
Irritability
Irritable
0000737
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Psychosis
0000709
Remnants of the hyaloid vascular system
0007968
Retinal detachment
Detached retina
0000541
Stereotypy
Repetitive movements
Repetitive or self-injurious behavior

[ more ]

0000733
Venous insufficiency
Poorly functioning veins
0005293
5%-29% of people have these symptoms
Abnormal pupil morphology
Abnormality of the pupil
Pupillary abnormalities
Pupillary abnormality

[ more ]

0000615
Abnormality of immune system physiology
0010978
Abnormality of the diencephalon
0010662
Abnormality of the helix
0011039
Aplasia/Hypoplasia of the cerebellum
Absent/small cerebellum
Absent/underdeveloped cerebellum

[ more ]

0007360
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder

[ more ]

0007018
Autism
0000717
Cachexia
Wasting syndrome
0004326
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Clonus
0002169
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay

[ more ]

0000823
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Diabetes mellitus
0000819
Ectopia lentis
0001083
EEG abnormality
0002353
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Glaucoma
0000501
Hallucinations
Hallucination
Sensory hallucination

[ more ]

0000738
Hypertonia
0001276
Malar flattening
Zygomatic flattening
0000272
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches

[ more ]

0002076
Muscle weakness
Muscular weakness
0001324
Muscular hypotonia
Low or weak muscle tone
0001252
Optic atrophy
0000648
Protruding ear
Prominent ear
Prominent ears

[ more ]

0000411
Scoliosis
0002650
Seizure
0001250
Self-injurious behavior
Self-injurious behaviour
0100716
Sensorineural hearing impairment
0000407
Sleep disturbance
Difficulty sleeping
Trouble sleeping

Cause

Norrie disease is caused by a change (mutation) in the NDP gene, which is located on the X chromosome.[1][2] It is inherited in an X-linked recessive manner.[1][2][3] The NDP gene provides instructions for making a protein called norrin, which affects the way cells and tissues develop. In particular, the norrin protein seems to play an important role in the development of retinal cells in the eye. It is also involved in creating a blood supply to tissues of the retina and the inner ear, and the development of other body systems. Mutations in the NDP gene can prevent the norrin protein from working correctly, resulting in the signs and symptoms of Norrie disease.[1][3]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    Because most males with Norrie disease (ND) have complete retinal detachment at the time of birth, surgical intervention after that time is typically not effective for preserving sight.[3] Furthermore, we were unable to find reports about restoring sight to affected individuals after sight has been lost. Individuals without complete retinal detachment may benefit from intervention;[3] however, vitrectomy and laser photocoagulation are reportedly challenging and often associated with poor outcome.[4] A more recent case report reported evidence that immediate, prophylactic laser treatment at birth may prevent retinal detachment and blindness.[4] The individual described in the study was known to be at risk and was diagnosed before birth via amniocentesis, and thus laser treatment shortly after birth was able to be performed.[4] The authors of this report state that although the results they achieved are encouraging, longer observation of a larger number of patients is needed to determine the effectivness of this new approach.[4]

    In some cases, surgery may be required when progression of the condition leads to increased pressure within the eye. Rarely, enucleation (removal) of the eye may be necessary to control pain.[3]

    For individuals with hearing loss, hearing aid augmentation is usually successful until middle or late adulthood. Cochlear implants may be considered when function is severely impaired.[3]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • Genetics Home Reference (GHR) contains information on Norrie disease. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Norrie disease. Click on the link to view a sample search on this topic.

            References

            1. Norrie disease. Genetics Home Reference (GHR). March 2007; https://ghr.nlm.nih.gov/condition/norrie-disease.
            2. Sims KB. Norrie Disease. National Organization for Rare Disorders (NORD). 2012; https://rarediseases.org/rare-diseases/norrie-disease/.
            3. Katherine B Sims. NDP-Related Retinopathies. GeneReviews. September 18, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1331/.
            4. Clement C. Chow et al. Laser Photocoagulation at Birth Prevents Blindness in Norrie's Disease Diagnosed Using Amniocentesis. Ophthalmology. December 2010; 117(12):2402-2406.

            Rare Endocrinology News