What are the symptoms? Norrie disease causes abnormal development of the blood vessels and tissues at the backs of the eyes, leading to retina detachments. The irises appear white when light is shone on them;Cataracts often develop;The irises and 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, which can lead to learning disability (see entry Learning Disability) or behavioural issues. Progressive sensorineural hearing loss (hearing loss of nerve origin) is a secondary symptom and in many patients can start in early childhood. 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. Some children and young people with Norrie are reported to have low muscle tone and joint hypermobility. Advice should be sought from Occupational therapy or physiotherapy support should there be functional difficulties. What are the causes? 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 is it diagnosed? 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. How is it treated? 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: Ophthalmologists examine the eyes and decide on appropriate treatment. Clinical Geneticists establish the genetic origin of the disease and to provide genetic counselling to the family. Paediatricians assess development in early childhood and to coordinate medical care and educational support as required. Audiologists carry out regular hearing tests and to advise on hearing aids or cochlear implants if required. Endocrinologists 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. Therapy support from Speech and Language Therapists, Occupational Therapists, Physiotherapists. Specialist Education Support will be required with key professionals being: Rehabilitation Officer for sensory impairmentQualified Teacher of the visually impairedQualified 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. Inheritance patterns and prenatal diagnosis Inheritance patterns 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. The vast majority of mothers of a boy with Norrie disease are carriers of 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. 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). Prenatal diagnosis Genetic testing methods change over time. A genetic doctor from an NHS genetic clinic 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. Is there support? The Norrie Disease Foundation Email: email@example.comWebsite: norriedisease.org.uk The Norrie Disease Foundation is a Registered Charity No. 1171274. The Foundation aims to raise awareness of the condition, promote research and to strengthen the Norrie network. They provide information for families and medical professionals. Group details reviewed December 2018.