Leber congenital amaurosis

Leber Congenital Amaurosis (LCA) Description

Leber congenital amaurosis, also known as LCA, is an eye disorder that is present from birth (congenital). This condition primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color.

Key Characteristics:

• Congenital: Present from birth
• Retinal Disorder: Primarily affects the retina
• Rare Genetic Condition: Caused by a mutation in one or more genes

According to [1], LCA is an eye disorder that primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. This condition can result from variants (also known as mutations) in at least 20 genes, all of which are necessary for the function of the retina and normal vision [2].

LCA should not be confused with Leber's hereditary optic neuropathy, which is a different disease also described by Theodor Leber [12]. It affects about 1 in 40,000 newborns [1] and is one of the most common causes of childhood blindness [14].

References:

[1] Context result 12 [2] Context result 2 [12] Context result 12

Severe Visual Impairment from Birth

Children born with Leber congenital amaurosis (LCA) typically have severe visual impairment or blindness from birth [1]. This condition usually develops in babies less than a year old, making it challenging for parents to detect any issues early on. One of the first signs that may be noticed is excessive eye rubbing by the child [1].

Reduced Vision and Electrical Activity

The retina's light-gathering cells (rods and cones) do not function properly in children with LCA, leading to reduced vision or blindness [2]. A crucial diagnostic indicator for this condition is the absence or reduction of electrical activity in the retina [2].

Autosomal Recessive Inheritance Pattern

Leber congenital amaurosis usually follows an autosomal recessive inheritance pattern, meaning both copies of the gene in each cell have variants [3]. This typically results in parents carrying only one copy of the altered gene and not displaying any symptoms themselves.

Common Symptoms

The common symptoms associated with Leber congenital amaurosis include:

• Severe visual impairment or blindness from birth
• Reduced vision that can often be detected by parents within the first few months [12]
• Light sensitivity (photophobia)
• Involuntary movements of the eyes (nystagmus)
• Extreme farsightedness

Rare Causes of Blindness

Leber congenital amaurosis is a rare type of inherited eye disorder that causes severe vision loss at birth, making it one of the most common causes of inherited blindness in childhood [4]. It affects two to three out of every 100,000 babies [5].

References: [1] - Context result 1 [2] - Context result 2 [3] - Context result 3 [4] - Context result 4 [5] - Context result 5

Leber congenital amaurosis (LCA) can be diagnosed through various tests, which are essential for confirming the condition and ruling out other potential causes of visual impairment.

Eye Examination: An eye care specialist will perform a comprehensive eye examination to assess the child's vision and detect any abnormalities in the eyes. This includes looking at the eyes from the outside as well as using instruments to examine the inside of the eyes [1].

Electroretinography (ERG): ERG measures the electrical activity in the retina, which can help diagnose LCA by detecting abnormal retinal function [2]. A Ganzfeld electroretinogram is a type of ERG that is often used for this purpose.

Optical Coherence Tomography (OCT) Scan: An OCT scan uses low-coherence interferometry to capture high-resolution images of the retina, which can help diagnose LCA by detecting abnormalities in the retinal structure [1].

Genetic Testing: Genetic testing can be performed to identify mutations in genes associated with LCA. This includes mutation scanning of the entire coding region, sequence analysis of select exons, deletion/duplication analysis, and targeted variant analysis [3]. A 28-gene panel that includes assessment of non-coding variants is also available for patients with a clinical suspicion or diagnosis of Leber congenital amaurosis [6].

Other Diagnostic Tests: Other diagnostic tests may include an optical coherence tomography (OCT) scan, which can help detect abnormalities in the retinal structure. A 28-gene panel that includes assessment of non-coding variants is also available for patients with a clinical suspicion or diagnosis of Leber congenital amaurosis [6].

It's essential to note that LCA is a rare genetic eye disorder, and affected infants are often blind at birth. Other symptoms may include crossed eyes, photophobia, and abnormal or absent pupillary responses [8]. A comprehensive diagnostic evaluation by an eye care specialist is necessary to confirm the diagnosis.

References: [1] The purpose of this overview is to increase the clinician's awareness of Leber congenital amaurosis (LCA) / early-onset severe retinal dystrophy (EOSRD) and its clinical phenotypes, genetic causes, and management. [11] [2] Koenekoop RK. An overview of Leber congenital amaurosis: a model to understand human retinal development. Surv Ophthalmol. 2004;49(3):379–398. [3] Core tip: Leber congenital amaurosis (LCA) is the most severe retinal dystrophy causing blindness before the age of 1 year. Clinical ophthalmological findings together with electroretinogram study, OCT imaging and retinal molecular-genetic technologies provide a precise diagnosis in these individuals. [12] [6] A 28-gene panel that includes assessment of non-coding variants is also available for patients with a clinical suspicion or diagnosis of Leber congenital amaurosis. [8] Leber congenital amaurosis is a group of severe congenital retinal conditions and the leading cause of inherited blindness in children. Symptoms, typically present in the first 6 months of life, include nystagmus, strabismus, photophobia, abnormal or absent pupillary responses, and cataracts.

Leber congenital amaurosis (LCA) is a severe congenital/early-onset retinal dystrophy that results in significant visual loss at an early age [4]. While there is no cure for LCA, various treatment options are being explored to improve vision and manage the condition.

Gene Therapy

One promising treatment approach for LCA is gene therapy. Gene therapy involves replacing or repairing a faulty gene with a healthy copy, which can help restore vision in individuals with LCA [5]. The FDA-approved gene therapy, Luxturna (voretigene neparvovec), has been shown to improve vision in patients with LCA due to RPE65 mutations [6][7].

Luxturna is administered via a one-time subretinal injection and requires a common retina surgery procedure called a vitrectomy. The treatment must be performed by an ophthalmologist with experience in injecting genes under the retina [15]. While Luxturna has been shown to improve vision, it's essential for patients to understand that this treatment is not a cure for LCA and may have varying degrees of success.

Other Treatment Options

In addition to gene therapy, other treatment options are being explored for LCA. These include:

• Gene augmentation: This involves introducing a healthy copy of the faulty gene into the retina [9].
• Oral drug therapy: Researchers are investigating various oral medications that may help slow down or halt vision loss in individuals with LCA [2].
• Intraocular drugs: Some studies have explored the use of intraocular injections to deliver medication directly to the retina, which may help improve vision in patients with LCA [9].

Current Research

Researchers are actively investigating new treatment options for LCA. For example, a recent study identified a compound that keeps light-sensitive photoreceptors alive in three models of Leber congenital amaurosis type 10 (LCA 10) [12]. This finding has potential implications for the development of new treatments for LCA.

In summary, while there is no cure for Leber congenital amaurosis, various treatment options are being explored to improve vision and manage the condition. Gene therapy, specifically Luxturna, has shown promise in improving vision in patients with LCA due to RPE65 mutations. Other treatment options, such as gene augmentation, oral drug therapy, and intraocular drugs, are also being investigated.

Leber congenital amaurosis (LCA) is a rare and severe form of retinal dystrophy that affects vision at birth or in early infancy. When diagnosing LCA, it's essential to consider other conditions that may present with similar symptoms. Here are some differential diagnoses for Leber congenital amaurosis:

• Hereditary optic atrophy: This condition is characterized by progressive loss of vision due to degeneration of the optic nerve. It can be inherited in an autosomal dominant or recessive pattern.
• Congenital optic atrophy: This is a rare condition where the optic nerve is damaged at birth, leading to severe visual impairment or blindness.
• Retarded myelinization of the optic nerve: This condition affects the development of the optic nerve, leading to impaired vision or blindness.
• Retinitis pigmentosa: A group of genetic disorders that affect the retina's ability to respond to light, leading to progressive vision loss.
• Alström syndrome: A rare genetic disorder characterized by progressive vision and hearing loss, as well as other systemic symptoms.
• Joubert syndrome: A rare genetic disorder affecting the development of the brain and eyes, leading to impaired vision and other neurological symptoms.

According to [3], Leber congenital amaurosis is also considered in the differential diagnosis of connatal blindness, which includes conditions such as hereditary optic atrophy, congenital optic atrophy, and retarded myelinization of the optic nerve. Additionally, [11] mentions that retinitis pigmentosa, Alström syndrome, and Joubert syndrome are part of the differential diagnosis for LCA.

It's worth noting that a precise diagnosis of Leber congenital amaurosis can be made through clinical ophthalmological findings, electroretinogram studies, OCT imaging, and retinal molecular-genetic technologies [10].