What are the other Names for this Condition? (Also known as/Synonyms)

• LCA (Leber’s Congenital Amaurosis)

What is Leber's Congenital Amaurosis? (Definition/Background Information)

• Leber’s Congenital Amaurosis (LCA) is a rare genetic disorder affecting the retina in infants. It is characterized by early development of severe visual impairment and even blindness during infancy
• The cause of Leber’s Congenital Amaurosis is attributed to mutation in genes that are involved in the normal functioning of retinal cells and light perception, which include RPE 65, CRB1 and CEP290 genes
• Children with parents, who are blood-related to each other, are more likely to be diagnosed with Leber’s Congenital Amaurosis
• The diagnosis of the condition requires detailed eye examination, electroretinography, and molecular genetic testing
• Subretinal injection gene therapy, which is a relatively new treatment, is still being developed to treat LCA. Surgical trials have been carried out and it has shown modest result in improving the child’s visual function and light sensitivity
• The efficacy of gene therapy is believed to improve in the near future, as scientists and clinicians develop better delivery system and calculation for effective dosage. With treatment, in a majority of individuals, the prognosis is generally good

Who gets Leber's Congenital Amaurosis? (Age and Sex Distribution)

• Leber’s Congenital Amaurosis is a very rare congenital disorder that is diagnosed in 2-3 individuals out of every 100,000 births
• Cases of LCA have been reported throughout the world, and there is no racial, ethnic or gender preference observed.

What are the Risk Factors for Leber's Congenital Amaurosis? (Predisposing Factors)

• Children with consanguine parents (blood-related parents) are more likely to be diagnosed with Leber’s Congenital Amaurosis

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Leber's Congenital Amaurosis? (Etiology)

Leber’s Congenital Amaurosis is a genetic disorder in which the function of the retina is impaired.

• The normal functioning of retina is sustained by the intricate interplay between many proteins within the retinal cells. Various genetic mutations which alter the structure or expression of proteins found in retinal cells have been found to be implicated in LCA
• Mutations in 14 known genes have so far been found to be associated with the disorder and they include: RPE65, CRB1, CEP290, AIPL1, CRX, GUCY2D, IMPDH1, LCA5, LRAT, MERTK, RD3, RDH12, RPGRIP1, and TULP1 genes
• Many of the genes (mentioned-above) code for proteins that are implicated in normal functioning of retinal cells. It should be also noted that there may be more genetic mutations, which are responsible for Leber’s Congenital Amaurosis that are yet to be discovered

What are the Signs and Symptoms of Leber's Congenital Amaurosis?

Individuals with LCA-related genetic mutation begin to display severe visual impairment shortly after birth, typically within the first year of life. The signs and symptoms of Leber’s Congenital Amaurosis may include:

• Development of severe visual impairment during infancy
• Abnormality in the retina
• Rapid, involuntary eye movement
• Slow or absence of pupillary response
• Extremely sensitive to light (photophobia)
• Severe farsightedness
• Frequent rubbing and pressing of the eye, known as Franceschetti's oculo­digital sign

How is Leber's Congenital Amaurosis Diagnosed?

The diagnosis of Leber’s Congenital Amaurosis is based on the signs and symptoms, the family medical history, electroretinography, and molecular genetic test. LCA diagnosis may involve:

• A thorough physical examination and evaluation of individual’s family medical history that is essential for diagnosis
• A primary eye examination to test the infant’s visual function will be needed as development of severe visual impairment during infant’s first year is a telling sign for diagnosis
• Electroretinography (ERG) may be performed to examine infant’s retina function. The ERG will reveal if the infant’s retina is sensitive to light; a normal ERG will help to rule out the possibility of Leber’s Congenital Amaurosis
• Molecular genetic testing can also be carried out to detect mutation in genes that are implicated in LCA to confirm diagnosis. Molecular genetic testing will require collection of the infant’s blood for analysis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Leber's Congenital Amaurosis?

The main complication of Leber’s Congenital Amaurosis is keratoconus, which is the bulging of cornea.

• Keratoconus alters the shape of the clear membrane, known as cornea, which lies on the surface of the eye
• This change in the shape of cornea may further impair the vision of individuals with amaurosis
• The cause of keratoconus is attributed to mutation in genes that are also implicated in LCA

How is Leber's Congenital Amaurosis Treated?

The treatment of Leber’s Congenital Amaurosis may involve the following:

• New treatment using gene therapy has been introduced in recent years to treat LCA, which was once thought to be incurable
• The RPE65 gene therapy treatment uses subretinal injection to deliver functional RPE65 gene into the retina of individuals with LCA caused by RPE65 gene mutation
• Surgical trials conducted so far have shown modest improvement in visual function and retina sensitivity

Very importantly, the surgical trials have proven to be safe. As more clinical trials are being conducted, gene therapy is believed to improve in efficacy and safety in the near future, helping more individuals with this congenital condition to improve their visual acuity.

How can Leber's Congenital Amaurosis be Prevented?

• Currently, there are no specific methods or guidelines to prevent Leber’s Congenital Amaurosis, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Leber’s Congenital Amaurosis

What is the Prognosis of Leber's Congenital Amaurosis? (Outcomes/Resolutions)

• Individuals with Leber’s Congenital Amaurosis caused by mutations in CRB1, LRAT, and RPE65 gene mutations tend to have visual acuity of 20/50. A 20/50 eye sight means that the individual with LCA needs to stand at 20 feet, to see an object that any other individual with a normal eyesight can see at 50 feet
• While most individual with LCA tends to have a relatively stable visual function, some have their visual function deteriorate progressively (gets worse slowly over time)
• Without therapeutic intervention, such as gene therapy, the visual function of individuals with LCA typically do not improve

Additional and Relevant Useful Information for Leber's Congenital Amaurosis:

Children with Leber’s Congenital Amaurosis tend to rub and poke their eyes repeatedly. Parents should discourage their children from such actions, as it may further injure their eye or even cause eye infection by introducing bacteria into the eye.