Leber congenital amaurosis 12

Leber congenital amaurosis-12 (LCA12) is a rare genetic eye disorder that affects infants from birth. The condition is characterized by several symptoms, including:

• Congenital nystagmus: This refers to an involuntary movement of the eyes that can be present at birth.
• Low vision: Individuals with LCA12 often have severely reduced visual acuity or are blind.
• Sluggish pupillary reflexes: This means that the pupils may not react normally to light.
• Absence of ocular pursuit: This refers to a lack of ability to track moving objects with the eyes.

These symptoms can be present from birth and are often associated with other eye disorders. LCA12 is one of several forms of Leber congenital amaurosis, which is a group of inherited retinal diseases characterized by severe impaired vision or blindness at birth.

According to some sources, LCA12 manifests itself in the first 6 months of life with significant visual loss and sensory, pendular nystagmus [8]. It's essential to note that this condition is rare and affects a small number of individuals worldwide.

Leber Congenital Amaurosis (LCA) 12, also known as LCA12, is a rare form of inherited eye disorder that causes severe vision loss at birth. The signs and symptoms of LCA12 are similar to those of other forms of Leber congenital amaurosis.

• Congenital nystagmus: This is the involuntary twitching or shaking of the eyes, which can be present from birth.
• Low vision: Individuals with LCA12 typically experience severe visual impairment, often resulting in blindness.
• Sluggish pupillary reflexes: The pupils may not react properly to light, making it difficult for individuals to adjust to changes in lighting conditions.
• Absence of ocular pursuit: This refers to the inability to track moving objects with the eyes.

These symptoms are typically present from birth and can be accompanied by other clinical findings such as refractive error, photophobia (sensitivity to light), photodysphoria (discomfort or pain in response to light), and oculodigital sign (a specific behavior where individuals poke, press, and rub their eyes with a knuckle or finger).

According to [3], the oculodigital sign is a characteristic feature of LCA12, where affected individuals exhibit poking, pressing, and rubbing their eyes with a knuckle or finger. This behavior often results in flashes of light.

The symptoms of LCA12 can vary from person to person, but they are generally severe and persistent. Early diagnosis and treatment are crucial for managing the condition and improving visual outcomes.

References: [3] - Franceschetti's oculo-digital sign is characteristic of Leber congenital amaurosis. [9] - Leber congenital amaurosis-12 (LCA12) is characterized by congenital nystagmus, low vision, sluggish pupillary reflexes, absence of ocular pursuit from birth.

Leber congenital amaurosis 12 (LCA12) is a rare genetic eye disorder that affects vision from birth. Diagnostic tests are essential to establish a diagnosis and provide insights into the underlying cause of the condition.

Electroretinography (ERG): ERG tests are often used to diagnose LCA12, as they measure the electrical activity in the retina. This test can help identify abnormal retinal function, which is characteristic of LCA12 [1].

Optical Coherence Tomography (OCT): OCT scans may also be performed to evaluate the structure and thickness of the retina. While not specific for LCA12, OCT can provide valuable information on retinal morphology [2].

Genetic Testing: Genetic testing is a crucial diagnostic tool for LCA12. It involves analyzing DNA samples from affected individuals or family members to identify mutations in the CEP290 gene, which is associated with LCA12 [3]. This test can confirm the diagnosis and provide information on the genetic cause of the condition.

Other Diagnostic Tests: In some cases, additional diagnostic tests may be performed to rule out other conditions that could present similarly to LCA12. These may include:

• Fundus examination: A detailed examination of the retina and optic nerve to assess for any abnormalities.
• Visual acuity testing: To evaluate the extent of visual impairment.
• Pupillary light reflex testing: To assess the function of the pupils.

It's essential to note that a comprehensive diagnostic evaluation by an eye care specialist, including ERG, OCT, and genetic testing, is necessary to establish a diagnosis of LCA12.

References:

[1] Koenekoop RK. An overview of Leber congenital amaurosis: a model to understand human retinal development. Surv Ophthalmol. 2004;49(5):379-398.

[2] Stone EM. Leber congenital amaurosis - a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture. Am J Ophthalmol. 2007;144(6):791-811.

[3] Genes. 2021;12(8), 1261. Early Detection and Diagnosis for Leber’s Congenital Amaurosis.

Treatment Options for Leber Congenital Amaurosis

Leber congenital amaurosis (LCA) is a severe congenital/early-onset retinal dystrophy that results in significant vision loss. While there are no curative treatments available, various therapeutic approaches have been explored to manage the condition.

• Gene Therapy: Gene therapy has shown promise in treating LCA caused by mutations in the RPE65 gene (LCA2). Studies have demonstrated safety and efficacy of adeno-associated viral gene therapy for this condition. [12][14]
• Voretigene Neparvovec-rzyl (Luxturna): In 2017, the US FDA approved Luxturna, a gene therapy for LCA2 caused by biallelic RPE65 mutations. This treatment has been shown to be safe and effective in improving vision in patients with this condition. [15]
• ATSN-101: ATSN-101 is another drug being investigated for the treatment of LCA. Studies have demonstrated durable, clinically significant improvements in vision at high doses, with no drug-related serious adverse events reported. [11]

Supportive Care

While these treatments show promise, it's essential to note that supportive care remains the primary approach for managing LCA. This includes correction of refractive error and other supportive measures to improve quality of life.

References

• Hauswirth WW, Aleman TS, Kaushal S, et al. Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular gene therapy. [12]
• Maguire AM, Simonelli F, Pierce EA, et al. Safety and efficacy of gene transfer for Leber's congenital amaurosis. [22]
• Cideciyan AV. Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Prog Retin Eye Res. 2010;29(5):398–427. doi: 10.1016/j.preteyeres.2010.04.002. [PMC free article] [Google Scholar]

The differential diagnosis of Leber congenital amaurosis (LCA) involves a range of conditions that can present with similar symptoms, making it challenging to diagnose accurately.

Conditions to Consider:

• Hereditary optic atrophy [6][8]: This is a condition where the optic nerve is damaged due to genetic factors, leading to vision loss.
• Congenital optic atrophy [6][8]: Similar to hereditary optic atrophy, this condition involves damage to the optic nerve present from birth.
• Retarded myelinization of the optic nerve [6]: This refers to a delay in the development of the fatty insulation (myelin) around the optic nerve, leading to vision problems.

Other Considerations:

• Leber congenital amaurosis itself is a group of inherited retinal diseases characterized by severe impaired vision or blindness at birth [7]. The differential diagnosis should take into account the genetic and hereditary aspects of LCA.
• Connatal blindness, which includes conditions like LCA, requires careful consideration of various factors to arrive at an accurate diagnosis [6][8].

Key Points:

• Differential diagnosis is crucial for accurately diagnosing Leber congenital amaurosis (LCA).
• Conditions like hereditary optic atrophy, congenital optic atrophy, and retarded myelinization of the optic nerve should be considered.
• LCA itself is a group of inherited retinal diseases with severe impaired vision or blindness at birth.

References: [1] by CH Huang · 2021 · Cited by 51 — [2] Oct 6, 2022 [3] Sep 10, 2024 [4] [5] by RG Coussa [6] [7] [8]