X-linked retinoschisis: symptoms, inheritance and care

The retina is the thin film of tissue lining the back of the eye. Retina UK explains that in XLRS the layers of cells within the retina split, which is what retinoschisis means, and this disrupts the transmission of signals from the light-sensitive photoreceptor cells to the brain. A characteristic feature is cystic spaces appearing in the macula, the central part of the retina.

The US National Library of Medicine’s MedlinePlus describes the condition as impairing the sharpness of vision in both eyes, because the macula is responsible for the sharp central vision needed for reading, driving and recognising faces. Occasionally side vision is affected as well, and MedlinePlus notes that in about half of affected people the splitting occurs in the periphery rather than the macula.

Retina UK says the first signs are typically poor visual acuity not correctable with glasses, with a wide range of severity depending on the amount and location of retinoschisis. MedlinePlus says the condition is usually diagnosed when affected boys start school and poor vision and difficulty reading become apparent. In more severe cases, squinting and involuntary eye movements (nystagmus) begin in infancy, and eyes that do not look in the same direction (strabismus) and long-sightedness (hyperopia) can be early features.

Diagnosis involves an eye examination by an ophthalmologist, who may see a spoke-wheel pattern in the macula, retinal imaging, and genetic testing for the RS1 gene. MedlinePlus notes that some people with the condition do not have an RS1 mutation, and in them the cause is unknown. In the UK, children are usually referred through paediatric ophthalmology and, for genetic confirmation, clinical genetics services.

• Reduced sharpness of vision that glasses do not fully correct.

• Difficulty reading or seeing detail at school age.

• Squint or wobbling eye movements in some children.

• Reduced side vision in some people.

• Sudden floaters, a curtain over vision or loss of vision, which need urgent eye assessment because they may signal a bleed or retinal detachment.

Retina UK describes the typical pattern: visual acuity may deteriorate slightly over the first and second decade of life, then remains relatively stable until the fifth or sixth decade, when slowly progressive retinal degeneration could occur and progress to legal blindness. MedlinePlus gives a similar account, with a decline in a man’s fifties or sixties.

Some people experience complications. Retina UK says XLRS may occasionally be complicated by vitreous haemorrhage, which is bleeding within the eye cavity, or retinal detachment, which may warrant surgery. A sudden shower of floaters, flashes of light, a dark shadow or a sudden drop in vision should be treated as an emergency: contact an eye casualty department, NHS 111 or A&E the same day.

XLRS is caused by mutations in the RS1 gene on the X chromosome. Females have two X chromosomes and can carry the faulty gene on one of them; because they have a healthy version on the other, female carriers are usually minimally affected. Males have one X chromosome, so a single faulty copy causes the condition.

Retina UK explains that male patients may never pass the condition to their sons, but their daughters become carriers. Female carriers have a 50% chance of passing the gene to each daughter, who becomes a carrier, and a 50% chance of passing it to each son, who is then affected. Genetic counselling is available through NHS clinical genetics services and can discuss testing of relatives and options when planning a family.

MedlinePlus estimates the prevalence at 1 in 5,000 to 25,000 males worldwide, while Retina UK cites an estimated 35,000 cases in the United States and Europe.

Retina UK states that there is currently no treatment for XLRS itself, but that there are many services and accommodative and assistive resources for people and families. It notes that cystic changes in the macula can fluctuate and that treatment with medicines may be attempted with variable results, and that surgery may be needed for haemorrhage or detachment.

Practical management in the UK commonly includes regular ophthalmology review, up-to-date glasses to make the most of the vision available, low-vision aids, and educational support so children can access reading and classroom material. Specialist teachers for children with vision impairment and low-vision services for adults may be able to advise; ask your ophthalmology team or local authority sensory team.

Retina UK notes ongoing research and clinical trials aimed at gene therapies to restore a working RS1 gene in the retina.

Retina UK is a UK charity that welcomes families affected by XLRS and runs a helpline, peer support groups and information about inheritance and research participation. Their page was professionally reviewed by a consultant vitreoretinal surgeon at Oxford Eye Hospital.

Ask your ophthalmologist about low-vision services, genetic counselling and whether you may be eligible for relevant research. Private ophthalmology or genetic testing can be considered for speed of access, but NHS clinical genetics generally coordinates family testing and counselling, and specialist inherited retinal disease clinics are based at certain NHS eye hospitals.