We are very thankful to Professor Wolfgang Berger; Professor Maria Bitner-Glindzicz; Professor Mehul Dattani; Mr Robert Henderson; Dr Ngozi Oluonye; Dr Tony Sirimanna and Mr Chien Wong for their help with compiling this information.
What Is Norrie Disease?
Norrie disease is a rare genetic condition causing blindness/severe visual impairment from birth.
In addition to this most affected individuals suffer from progressive hearing loss often starting in early childhood.
Some also have issues with cognitive development, circulation, delayed or arrested puberty, and sexual dysfunction. It affects mainly boys.
Norrie disease is a congenital genetically inherited eye condition.
It is an X-linked recessive condition, caused by a mutation of the NDP gene on the X-chromosome.
A recessive condition is a condition where two copies of each chromosome need to be present for the disease to occur. However, as Norrie is an X-linked condition, it would occur in every boy born with a faulty X-chromosome. Norrie disease therefore usually occurs in boys, because boys only have one X-chromosome.
A girl with one abnormal X-chromosome will be a carrier but will not be affected if the other X-chromosome does not have the abnormal gene. Carrier females have a 50% chance of passing the gene unto the unborn male.
How common is Norrie Disease?
Around 40 cases in the UK are known and 500 globally. However, the Norrie community feel there are probably many more people with Norrie who have not been diagnosed.
Norrie disease causes abnormal development of the blood vessels and tissues at the backs of the eyes. This affects the retina and; causing abnormal development to this sensitive part of the eye that detects light and colour, leading to retinal detachment. As a result, the irises (the coloured part of the eye) appear white when they have light shone on them; a symptom called leukocoria. Cataracts often develop. The irises and the entire eyeball may shrink during the first few months of life, causing profound visual impairment.
Visual impairment of any cause can create developmental challenges in some individuals which may result in developmental delay and later on, learning disability. Communication and behaviour can also be affected. Some (approximately 30%-50%) of boys with Norrie disease have developmental delay, learning disability or behavioural issues.
Progressive sensorineural hearing loss (hearing loss of nerve origin) is a secondary symptom of Norrie disease and in many patients can start in early childhood. The hearing loss may be significant enough for hearing aids to be prescribed and in some cases, cochlear implants. More research is needed to gain a better understanding of how individuals with Norrie disease may be affected by hearing loss.
Norrie disease has been associated with peripheral venous insufficiency where the flow of blood through the veins is inadequate, causing blood to pool in the legs. Varicose veins and leg ulcers can develop.
Norrie disease has also been associated with short stature, delayed or arrested puberty, and sexual dysfunction. To date, the pathophysiological basis underlying the growth and pubertal issues remains largely unknown.
Diagnosis and mangement – What you can expect
Norrie disease is diagnosed on the basis of clinical eye findings if the individual presents with congenital blindness. Clinical genetic testing is available to help confirm the diagnosis.
The management of Norrie disease is targeted towards establishing the extent of the disease. This determines the needs of the individual and is likely to require the coordinated efforts of a team of specialists:
The role of the Ophthalmologist would be to examine the eyes and decide on appropriate treatment. This could include removal of cataracts, treatment for glaucoma, laser treatment, shells for the eyes (for structural and cosmetic purposes) or prosthesis. Those who have not completely lost their vision have been treated with surgery or laser therapy in infancy in the US. Children in the UK are rarely offered eye surgery. If surgery is offered, it would be to prolong light perception vision. However, there is no good data available yet as to whether this surgery achieves this aim, and there are significant risks associated with surgery.
As Norrie disease is a rare condition, you may wish an appointment to see a paediatric ophthalmologist at GOSH with a particular interest in this condition. Please discuss this with your local ophthalmologist, GP and /or paediatrician who will be able to make the appropriate referral. Your initial and subsequent appointments may provide you with an opportunity to discuss further medical referrals to other services at GOSH such as Audiology or Endocrinology if these are clinically indicated. (see references to Audiologists and Endocrinologists below).
The role of the Clinical Geneticist is to establish the genetic origin of the disease and to provide genetic counselling to the family.
The role of the Paediatrician is to assess development in early childhood and to coordinate medical care and educational support as required.
The role of the Audiologist is to carry out regular hearing tests and to advise on hearing aids or cochlear implants if required.
Paediatric endocrinologists who work within the multidisciplinary team will ensure that any growth and pubertal issues are dealt with promptly, and growth of children and young people with Norrie disease is optimised. Growth must be monitored carefully by the local team, and children must be referred to a paediatric endocrinologist if there are concerns with respect to growth, and certainly, all children must be referred by the age of 11-12 years so that puberty can be monitored carefully. Management of growth and pubertal disorders may include the use of hormones such as growth hormone and testosterone. However each child must be carefully evaluated and the most appropriate investigations performed. Treatment must then be directed appropriately.
Therapy support (may include)
Speech and Language Therapist
Specialist Educational Support
Specialist Education Support will be required with key professionals being:
Rehabilitation Officer for sensory impairment
Qualified Teacher of the visually impaired
Qualified Teacher for the hearing impaired
Other healthcare professionals may also be needed to systematically and comprehensively plan the treatment and management of the condition on a case by case basis.
GOSH Developmental Vision Clinic (DVC) is setup to see babies and young children with severe-profound visual impairment up to the age of 5 years to provide guidance on developmental progress, and answer any other questions that families may have about their child’s vision or development. This is in addition to the crucial support that hopefully families are getting from their local services, particularly the QTVI. Families should be linked into the local child development service (Community Paediatricians and therapists).
GOSH DVC service is a ‘tertiary’ service (GPs are primary, Community Paediatrics/Child Development Centre is secondary, specialist hospitals are tertiary) and can only take referrals from a Community Paediatrician or Hospital Paediatrician or from an Ophthalmologist.
Norrie disease is caused by a genetic misprint (mutation) in the ND pseudoglioma (NDP) gene which is located on the X-chromosome. Norrie disease is passed on in families in an X-linked recessive pattern of inheritance.
Females (XX) have two copies of the NDP gene, one on each of their two X-chromosomes. Males (XY) have only one copy on their single X-chromosome. Norrie disease occurs in males when there is a misprint in their single copy of the NDP gene. Otherwise healthy females can carry an altered NDP gene with the working copy on their other X-chromosome usually being enough to compensate for this, preventing them from developing the condition. Women who are carriers of Norrie disease have a 1 in 2 (50%) chance of passing the condition on to each son they have. Each of their daughters has a 1 in 2 (50%) chance of being a carrier of the condition. When a man with Norrie disease has children he will pass on his X-chromosome to all his daughters and so all (100%) daughters will be carriers of Norrie disease. None of the sons of a father with Norrie disease will inherit the condition from him as they will get their single X- chromosome from their mother.
The vast majority of mothers of a boy with Norrie disease are carriers of the condition. Very occasionally Norrie disease can occur due to a new spontaneous (de novo) mutation, without the mother actually being a carrier of the condition. If the mother has had carrier testing for Norrie disease and has not been found to be a carrier then the chance of her having another child with a Norrie gene alteration is low but still slightly higher than that of the general population. This is because of the very small possibility of there being a few egg cells in her ovaries that have a Norrie gene alteration (a situation known as germline mosaicism).
Genetic Services And Testing
Genetic testing methods change over time. A genetic doctor from an NHS genetic clinic (www.bsgm.org.uk/information-education/genetics-centres) can arrange testing of the NDP gene where appropriate, review the inheritance pattern and provide up-to-date management advice. Families are welcome to seek advice at various times of life from the genetic service or paediatrician. For example, when a child growing up with Norrie disease or their siblings want more details, they could attend the genetic clinic to ask about the condition for themselves.
The information on these pages represents current understanding of Norrie disease and has been taken from research to date and clinical findings of patients with Norrie disease. However, much more research is needed to get a better picture of how Norrie disease affects each individual. As and when new research reveals more information, these pages will be updated.
The Norrie Disease’s mission is twofold:
To promote and raise funds for pioneering research towards a better understanding of Norrie disease with the ultimate aim of developing gene therapies
To provide vital support to families with a diagnosis of Norrie disease
Laboratory study into hearing loss
With thanks to funding from Newlife, The Charity for Disabled Children and Sparks, Children’s Medical Charity the Norrie Disease Foundation are currently supporting a laboratory study at UCL Great Ormond Street Institute of Child Health into Norrie disease hearing loss. The research is aimed at developing an understanding of when and where in the Norrie ear the hearing loss occurs and if and when this can be treated by gene therapy.
This is a 3 year study which started in 2017 and is a huge step towards our ultimate goal of either preventing or reducing hearing loss so that people with Norrie disease do not end up deaf as well as blind.
Professor Maria Bitner-Glindzicz who very sadly died in September 2018 was leading this research but we are pleased to confirm that colleagues at UCL Great Ormond Street Hospital have stepped in to ensure this work continues.
In 2017-2018 Dr Amina Al-Yassin, Clinical Fellow in Genetics at Great Ormond Street Hospital conducted 22 face to face family studies to help the team at Great Ormond Street Hospital build a good idea of the issues experienced by people with Norrie disease and their journeys in the healthcare system.
One of the reasons for this study, is that if treatments for some of the complications of Norrie become available in the future, researchers need to know who to treat (everyone or just some people?), when to treat (before too much damage has been done) and how to tell if treatment has worked or not (the person might have fewer complications or a less severe medical problem than might be expected for a person of their age with Norrie). This is called a ‘natural history study’ which means a study of what normally happens over time in a particular medical condition and we need to have this information if we want to offer new treatments.
Norrie disease patient registry
Currently there is no central repository for patients diagnosed with Norrie disease which makes it much harder to undertake research in this area. This is why we are thrilled to announce that we are working with the world-renowned Great Ormond Street Hospital, London to set up a Norrie disease patient registry. The registry will have European focus with intention to collaborate globally.
This page is designed to give links to useful resources and is a space to share good ideas to help our young people. I will try to make suggestions for a whole range of ages and abilities. A great source of information for you though will be your child’s QTVI (Qualified Teacher of Vision Impairment) or VI team. If you are not currently in touch with your local VI Team, you can get contact details and other information from their Local Offer website. Just type in the county/borough you live in followed by Local Offer into an internet search engine. Pinterest is also a good source for getting ideas.
The NDF Educational School Leaflet aims to provide general information about Norrie Disease (ND), its management and how to support the education of children and young people in schools and educational settings.
You will find this leaflet useful if you work in a school or other educational setting with children or young people with ND.
If you are the parent or carer of a child or young person with ND, then you could use this guide to engage with the school or educational setting about your child’s needs.
Braille is a system of raised symbols that can be read by the fingers of people who are visually impaired. A braille cell is made up of six dots, arranged in two parallel lines of three (like the arrangement of a six on dice or dominoes). Parents, and those that may work with a child with a vision impairment, would ordinarily read braille with their eyes if they are sighted.
There are two types of braille. Grade 1, or uncontracted braille, is a code with one symbol for each letter of the alphabet and a few other symbols for punctuation and numbers. Grade 2, or contracted braille, uses the same alphabet code but has lots of extra signs for common words and combinations of letters.
The VI team that work with your child will be able to explain more to you about braille and how it will be taught to your child.
If you want to learn braille yourself, there are courses that you can pay to do with the RNIB – more information about the courses can be found on the RNIB website. www.rnib.org.uk
There is also a free online course that you can do, for more information click on the following link: www.uebonline.org
Children can learn to write Braille on a Perkins Brailler, this is a mechanical writing machine for producing braille.
Prior to learning braille, children need to develop motor skills and touch discrimination. This is so that they can use their fingers to read the braille through touch. They also need to have enough strength in their fingers to be able to use a braille machine.
There are lots of fun activities to suit all ages and abilities, from playing with playdough, using peg boards, popping bubble wrap, squeezing toys, sorting shapes – the list goes on! Again if your child has a QTVI, they will have lots of suggestions of activities you can do with your child.
Braille books can be borrowed from a number of places.
ClearVision is a postal lending library of children’s books designed to be shared by visually impaired and sighted children and adults. They have lovely tactile books and picture books that can be enjoyed by all. Borrowing books from them is a great way to introduce children to feeling braille before they learn to read. www.clearvisionproject.org