Course:MEDG550/Student Activities/Stargardt Disease

Overview:

Stargardt Disease (which may also be known as Juvenile Macular Dystrophy, fundus flavimaculatus, or STGD1) is an inherited condition which affects vision in both eyes. Symptoms may look like age-related macular degeneration (common vision issues seen in older adults); however, Stargardt has a much younger onset age from childhood to teen years. Stargardt disease type 1 is the most common form of juvenile macular dystrophy (i.e. childhood-onset progressive blindness).

Medical:

• Prevalence: 1 in 8000 to 1 in 10,000 people (0.0125% to 0.0100%)
  

  Figure 1. Snellen Chart. An ophthalmologist (eye doctor), Howard Snellen, developed this chart to measure visual acuity in 1862.
• Onset/Progression
  • Generally, children between 10 and 15 years old begin to experience symptoms.
  • The age of onset can indicate the severity (generally, earlier onset = more severe).
  • How the disease progresses may vary. Typically, visual acuity (ability to see shapes and details at a certain distance, tested using a vision test that shows black letters on a white background; Figure 1) will decrease from 20/20 (normal vision) to 20/70 or even 20/200.
    • In the fraction describing vision, the top number is the distance the person can see.
    • The bottom number shows how far someone with typical sight can see.

• Symptoms: There can be some differences in what having this disease looks like, but it always affects both eyes. Often, symptoms are presented on a spectrum, but some of the general symptoms are:
  • sensitivity to light
  • colour-blindness
  • Loss of central vision (grey, dark, or hazy spots in the middle of your vision)
  • requiring more time to adjust when going between bright and dark rooms or areas

• Diagnosis
  • Tests performed by an eye doctor:
    • Pupil dilation and retina examination (doctor gives you eyedrops to make your pupils bigger, and then they look at your retina).
    • Fluorescein angiography (inject a yellow dye, dilate the eyes as described above, and photograph the eye's blood vessels).
    • Visual acuity (see Figure 1).
  • Genetic Testing: often used to confirm a diagnosis.

• Treatment/Management: Unfortunately, there is currently no approved treatment for this condition, but there are steps you can take to slow the progression of vision loss
  • Protect your eyes from sunlight (e,x. wearing sunglasses/hats when outside).
  • Do not consume too much vitamin A (only consume the recommended daily amount).
  • Avoid smoking.
  • Visit your eye doctor regularly for check-ups.

Figure 2. Cross-section of the eye. This diagram shows some of the main structures of the eye, including the retina and the macula, which are both affected by Stargardt Disease.

Figure 3. A) Colour photo of the retina showing yellow-white flecks (lipofuscin) that develop on and around the macula as Stargardt Disease progresses. B) A second image of the same eye using a different method that makes the fat deposits easier to see.

Genetics:

How?

The changes that cause Stargardt Disease are in a gene called ABCA4. This gene helps make a protein that cleans up fat in the macula (a small part of the retina in the eye responsible for seeing - Figure 2). When this gene does not work, the fat is not cleaned up properly and makes little yellowish flecks (called lipofuscin) that can be seen by an eye doctor(see Figure 3). The build-up of fat causes the cells in the eye that are in charge of processing colour and light and sending signals to the brain to die.

Inheritance: Every person has two copies of each gene, one from mom and one from dad. Stargardt is inherited in what is called an autosomal recessive manner. Autosomal recessive means that it can affect boys and girls equally, and only when a person has two copies of a gene change are they affected by the condition. Typically, two unaffected parents, each carrying one copy of the gene change, pass it down to their child, who will be affected.

Figure 4. Autosomal Recessive Inheritance. This diagram shows how an autosomal recessive (AR) condition, like Stargardt, can be passed down in a family.

Figure 4. When two carrier parents (carrier = an individual that has one copy of the gene change) have a child, there is a:

• 25% chance of having an unaffected child (1/4)
• 50% chance to have an unaffected carrier child (2/4 or 1/2)
• 25% chance of having an affected child (1/4)

Other:

While this page discussed STGD1 (Stargardt disease type 1), it should be known that there are also other types of macular dystrophy called "Stargardt-like diseases" because the symptoms are similar to STGD1; however, they have different causes and are passed down in families differently:

• STGD2
• STGD3
• STGD4

If you are concerned about Stargardt-like diseases, please consult your healthcare provider.

Patient Resources:

What you should know about Stargardt Disease

NIH National Eye Institute: Stargardt Disease

Fighting Blindness Canada: Stargardt Disease

Fighting Blindness Canada: Genetic testing for inherited retinal diseases BC

Genetic Counselling:

Consulting with a genetic counsellor could benefit individuals who have a child with Stargardt disease or who are known carriers. A genetic counsellor will be able to explain the common symptoms of the condition and genetic testing benefits/limitations, as well as educate patients on their options.

Preconception counselling considerations:

• Consanguinity (two parents being related by blood) will increase the chances of a couple having an affected child.
• If both parents are known carriers, prenatal genetic diagnosis may be offered (amniocentesis or chorionic villus sampling).
  • Chorionic villus sampling (CVS): prenatal diagnostic test performed between 11 and 13 weeks gestational age, where a small piece of the placenta is obtained for testing.
  • Amniocentesis: a prenatal diagnostic test performed after 15 weeks of gestational age, where some fluid from around a fetus is removed for testing.

Psychosocial:

Parents may feel guilt if they are unaware of their carrier status and have a child with Stargardt. They also may worry about the quality of life for their child when they start losing their vision. This should be taken into consideration when speaking with patients, and it's important to normalize and validate patients feelings surrounding their specific circumstance(s). Additionally, there are low vision aids, assistive technologies, and supports that may be available to help make the affected person's life easier.

Affected patients report eye and non-eye symptoms that affect other physical, mental, and social areas of their lives. They may experience a wide range of emotions, including, but not limited to, annoyance, anger, irritability, exasperation, and worry. The worry described by patients was not only regarding the progression of their vision loss and how that will affect their lives but also how others see them. Also reported was that some individuals with Stargardt disease have a difficult time discussing their disease with others (n=10), some actively avoid talking about it (n=3), and some hide their disease altogether (n=8).