Leber congenital amaurosis (LCA) is a rare inherited eye disease. The condition primarily affects the light-sensitive area at the eye's back wall that detects light and color (retina). The pupils also don't typically respond to light, and the transparent front eye portion (cornea) may be abnormally thin and cone-shaped, a disorder called keratoconus. LCA’s specific pointer is a distinct behavior called Franceschetti's oculo-digital sign, which involves pressing, poking, and rubbing the eyes with a finger or knuckle. Experts think that Franceschetti's oculo-digital sign may be responsible for the keratoconus and deep-set eyes in children with the condition. Typically, children with the disorder have significant visual impairment starting in infancy.
Also Known As
- Leber abiotrophy
- Leber's amaurosis
- Congenital retinal blindness
There are at least 13 types of LCA, which are differentiated by their vision impairment patterns, genetic cause and related eye disorders.
Causes & Risk Factors
LCA is a monogenic condition, and at least 27 genes are believed to be involved. The genes are essential for normal vision and play various roles in retinal development and function. This includes the normal growth of the light-sensitive cells called photoreceptors, and converting light into electrical signals relayed to the brain, a process known as phototransduction. Thus, mutations in any of the genes can lead to early loss of vision.
The gene mutations are responsible for about 80-90 percent of reported LCA cases. The genes that cause the other 10-20 percent of the cases are not known. Generally, LCA has an autosomal recessive inheritance fashion. Recessive genetic diseases arise when a child receives two copies of a defective gene for the same trait, one from each parent. So, there are two copies of the abnormal gene in each cell.
The disorder has an autosomal dominant inheritance pattern when it occurs due to OTX2, CRX, or IMPDH1 gene mutations. Dominant genetic disease can occur with only one copy of the defective gene in each cell. Often, the child receives the gene mutation from an affected parent. However, some instances arise from new mutations and affect children without a family history of the condition.
The significant risk factor is affected parent(s)with a mutated gene responsible for LCA subtypes.
Signs & Symptoms
In many cases, LCA infants are blind at birth. In other cases, a decrease in visual responsiveness at birth is the initial indication of the disorder. Other symptoms may include:
- Severe vision loss
- Strabismus (crossed eyes)
- Abnormal retinal pigment
- Hyperopia (extreme farsightedness)
- Irregular or absent pupillary response
- Photophobia (increased light sensitivity)
- Enophthalmos (sunken or deep-set eyeballs)
- Cataracts (clouding of the natural eye lenses)
- Nystagmus (rapid, involuntary eye movements)
In sporadic cases, infants may manifest with developmental delay, hearing loss, and intellectual disability.
The eye specialist reviews the patient's medical history and symptoms and conducts physical and ophthalmological examinations and laboratory tests to diagnose. S/he may use electroretinography (ERG) to evaluate visual function by assessing activity in the retina. Typically, infants with LCA lack or exhibit decreased retinal electrical activity. S/he can also order molecular genetic testing for gene mutations associated with LCA. Clinical signs and symptoms guide the doctor in determining which genes to test for and in what order.
Other tests may include:
- Optical coherence tomography (OCT) of the retina
There is no substantial LCA cure or treatment. Thus, LCA treatment is symptomatic and supportive. The US Food and Drug Administration (FDA) has approved Voretigene neparvovec-rzyl, a gene therapy to treat confirmed cases of retinal dystrophy linked to biallelic RPE65 mutation.
Prognosis & Long-Term outlook
Generally, visual impairment is stable, but it can gradually deteriorate over time. Patients can benefit from refractive error correction, low-vision aids when possible, and most favorable access to educational and work-related opportunities.
Prevention & Follow Up
LCA is not preventable. Close follow-up of infants with LCA is recommended. Genetic counseling is recommended for families with LCA children.