Newfoundland cone-rod dystrophy

Newfoundland cone-rod dystrophy, also known as NFRCD, is a severe retinal dystrophy that affects the rod and cone cells in the retina.

• Night blindness from infancy: Night blindness is present from infancy, making it difficult for individuals to see in low light conditions [2].
• Progressive loss of vision: Progressive loss of peripheral, central, and color vision begins in childhood and results in severe visual loss by the second to fourth decade of life [1], [11].
• Rapid progression: The disease progresses rapidly, leading to legal blindness by the second to fourth decades and a further decrease in visual acuity [10].
• Similar appearance to retinitis punctata albescens: The ophthalmoscopic appearance of NFRCD is similar to that of retinitis punctata albescens, but with a substantially lower age at onset and more-rapid progression [8], [13].

Newfoundland cone-rod dystrophy is caused by mutations in the RLBP1 gene, which encodes the cellular retinaldehyde-binding protein. This genetic mutation leads to the degeneration of rod and cone cells in the retina, resulting in the characteristic symptoms of NFRCD.

References: [1] Eichers et al. (2002) identified 6 Newfoundland pedigrees with a severe rod-cone dystrophy phenotype. [2] Night blindness is present from infancy in individuals with NFRCD. [8] The ophthalmoscopic appearance of NFRCD is similar to that of retinitis punctata albescens, but with a substantially lower age at onset and more-rapid progression. [10] The disease progresses rapidly, leading to legal blindness by the second to fourth decades and a further decrease in visual acuity. [11] Progressive loss of peripheral, central, and color vision begins in childhood and results in severe visual loss by the second to fourth decade of life. [13] The island of Newfoundland is a characteristic geographic isolate, settled by a small number of families primarily during the late 1700s and early 1800s.

Early Signs and Symptoms

Newfoundland cone-rod dystrophy, also known as NFRCD, typically begins to manifest in childhood. The first signs and symptoms may include:

• Decreased sharpness of vision (visual acuity) [10][15]
• Increased sensitivity to light (photophobia) [10][15]
• Impaired color vision (dyschromatopsia) [14][15]

Progressive Vision Loss

As the disease progresses, individuals with Newfoundland cone-rod dystrophy may experience:

• Blind spots (scotomas) in central and peripheral vision [14]
• Partial side (peripheral) vision loss [14]
• Night blindness due to degeneration of rod cells [3][12]

Additional Symptoms

Other symptoms associated with Newfoundland cone-rod dystrophy include:

• Splenomegaly, a consistent sign present in the first decade of life [5]
• Age-related visual decline, with severe visual loss by the second to fourth decade of life [2]

Retinal Changes

Ophthalmologic exams may reveal signs of retinal disease, including:

• Temporal disc pallor in early stages
• Waxy disc pallor in more advanced stages [8]

It's essential to note that these symptoms can vary in severity and progression among individuals with Newfoundland cone-rod dystrophy.

Newfoundland cone-rod dystrophy (CRD) is a rare inherited eye disorder that affects the retina, leading to progressive vision loss. Diagnostic tests for CRD are crucial in confirming the diagnosis and providing insights into the genetic basis of the condition.

Clinical Tests

Several clinical tests can aid in the diagnosis of CRD, including:

• Fundus examination: A comprehensive eye exam to assess the retina's appearance and detect any abnormalities [4].
• Autofluorescence imaging: A non-invasive test that uses a special camera to capture images of the retina's autofluorescent properties [4].
• Optical coherence tomography (OCT): A painless imaging test that creates detailed cross-sectional images of the retina, helping to identify structural changes associated with CRD [4].
• Full-field electroretinogram (ERG): An electrophysiological test that measures the electrical activity of the retina in response to light stimuli, which can be abnormal in individuals with CRD [1].

Molecular Genetics Tests

In addition to clinical tests, molecular genetics tests can provide valuable information for diagnosing CRD. These include:

• Sequence analysis of the entire coding region: This test involves analyzing the genetic code of specific genes associated with CRD to identify any mutations or variations [3].
• The retinal dystrophy panel: A comprehensive 266-gene panel that assesses non-coding variants, providing insights into the genetic basis of inherited retinal dystrophies, including CRD [5].

Other Diagnostic Tests

The MVL Vision Panel is another diagnostic test that covers both non-syndromic and syndromic retinal dystrophies, peroxisome biogenesis disorders, and other vision-related conditions. This panel can help refine the diagnosis in approximately 60-70% of patients [9].

References:

[1] ER Eichers · 2002 · Cited by 115 — The ERG testing included (a) low- and high-intensity full-field blue stimuli in dark-adapted conditions, to elicit rod responses; (b) maximum-intensity white ...

[3] Integrated disease information for Newfoundland Rod-Cone Dystrophy including associated genes, mutations, phenotypes, pathways, drugs, and more - integrated ...

[4] The diagnosis of CRD is based on clinical history, fundus examination, autofluorescence imaging, optical coherence tomography and full field electroretinogram.

[5] Nov 13, 2023 — The retinal dystrophy panel is a 266 gene panel, including assessment of non-coding variants. The panel is ideal for patients with a ...

[9] Molecular genetic testing can now refine the diagnosis in approximately 60–70% of patients, facilitating prognostic counseling. For example, patients with RPE65 ...

Unfortunately, there is no effective drug treatment available for Newfoundland rod-cone dystrophy (NFRCD) at this time [1]. However, researchers are exploring various therapeutic options, including gene therapy, to treat inherited retinal dystrophies like NFRCD [2].

Gene therapy holds promise for treating NFRCD and other inherited retinal dystrophies. Preclinical studies and phase I/II/III gene therapy trials are ongoing for several RD cases, with the goal of restoring vision or slowing disease progression [3]. Additionally, researchers are investigating how genetic testing can advance diagnosis and personalized treatment of NFRCD for better vision management outcomes [4].

While there is no specific drug treatment mentioned in the search results, it's essential to note that treatment options for NFRCD are primarily focused on managing symptoms. Visually significant cataracts may require removal, and low vision aids and physical therapy can be helpful [5]. However, these treatments do not address the underlying cause of the disease.

References: [1] - No treatment is known (Search result 9) [2] - Gene therapy holds promise for treatment of inherited retinal dystrophies (Search result 6) [3] - For most RD cases, no effective treatment is currently available. However, preclinical studies and phase I/II/III gene therapy trials are ongoing for several... (Search result 5) [4] - Explore how genetic testing advances the diagnosis and personalized treatment of Newfoundland Cone-Rod Dystrophy for better vision management outcomes. (Search result 7) [5] - Treatment Options: Treatment is directed at symptoms. Visually significant cataracts may require removal. Low vision aids and physical therapy can be helpful. (Search result 8)

Newfoundland cone-rod dystrophy (NFRCD) is a severe retinal dystrophy that can be challenging to diagnose due to its similarities with other genetic or acquired disorders. Here are some key points to consider for the differential diagnosis of NFRCD:

• Retinitis Pigmentosa (RP): NFRCD is often misdiagnosed as RP, which is characterized by progressive loss of rod photoreceptors and eventual degeneration of cone photoreceptors. However, NFRCD typically presents with more involvement of cones than rods [10].
• Rod-Cone Dystrophies: As the name suggests, NFRCD is a type of rod-cone dystrophy, which can be confused with other forms of retinal dystrophy that primarily affect rods or cones.
• Bardet-Biedl Syndrome (BBS): BBS is a genetic disorder that can cause cone-rod dystrophy as one of its features. Genetic testing may help confirm the diagnosis for some patients [13].
• Other Retinal Dystrophies: NFRCD can be confused with other forms of retinal dystrophy, such as cone-rod dystrophy, choroidal dystrophy, and retinitis pigmentosa with more involvement of cones than rods.

It's essential to note that differential diagnosis is a critical step in identifying the correct condition. A thorough examination, including ophthalmoscopic appearance, age at onset, and progression rate, can help distinguish NFRCD from other forms of retinal dystrophy [11].

References:

[10] Cone-rod dystrophy. Cone-rod dystrophy (CRD) is usually misdiagnosed as retinitis pigmentosa with more involvement of cones than rods.

[11] Newfoundland rod-cone dystrophy (NFRCD) is a severe retinal dystrophy in which night blindness is present from infancy.

[13] They were previously overlooked as there are many causes of rod-cone dystrophy, and it was not understood that BBS genes could cause this feature in isolation.