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Retinoblastoma

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Description: Retinoblastoma is a rare malignant tumor of the retina that primarily affects young children and can lead to vision loss or death if untreated.
Type: Retinoblastoma is a type of eye cancer that primarily affects young children. The Type of genetic transmission can be either hereditary or non-hereditary (sporadic). The hereditary form follows an autosomal dominant pattern of inheritance, meaning that just one copy of the altered gene (RB1 gene) inherited from either parent can increase the risk of developing retinoblastoma.
Signs And Symptoms: Retinoblastoma is the most intrusive intraocular cancer among children. The chance of survival and preservation of the eye depends fully on the severity. Retinoblastoma is extremely rare as there are only about 200 to 300 cases every year in the United States. Globally, only 1 in about 15,000 children have this malignancy, though rates continue to increase.Intraocular malignancies are relatively more frequently treated than extraocular malignancies, likely due to a relatively earlier detection and subsequent treatment. Pediatricians may screen infants with annual vision tests, in which anomalies can be detected. During a red reflex test, light from an ophthalmoscope goes through transparent parts of the eye and reflects off the ocular fundus. If retinoblastoma is present, it may partially or fully impede light transversing this path. This may result in an abnormal red reflex or leucocoria, which can be a common indicator of retinoblastoma (when light is reflected by the tumor, the regular view of the red retina is blocked). The retinoblastoma may be visible as a whitish, translucent mass. If the tumor has not spread and is contained within the eye, chances of successful treatment are favorable. If initial signs are ignored or diagnosis is significantly delayed, outcomes and prognosis worsen. The effects of retinoblastoma may spread outside the eye, sometimes resulting in proptosis. Retinoblastoma that has spread may be significantly more difficult to treat. The most common and obvious sign of retinoblastoma is an abnormal appearance of the retina as viewed through the pupil, the medical term for which is leukocoria, also known as amaurotic cat's eye reflex. Other signs and symptoms include deterioration of vision, a red and irritated eye with glaucoma, and faltering growth or delayed development. Some children with retinoblastoma can develop a squint, commonly referred to as "cross-eyed" or "wall-eyed" (strabismus). Retinoblastoma presents with advanced disease in developing countries and eye enlargement is a common finding.Depending on the position of the tumors, they may be visible during a simple eye examination using an ophthalmoscope to look through the pupil. A positive diagnosis is usually made only with an examination under anesthetic (EUA). A white eye reflection is not always a positive indication of retinoblastoma and can be caused by light being reflected badly or by other conditions such as Coats' disease.The presence of the photographic fault red eye in only one eye and not in the other may be a sign of retinoblastoma. A clearer sign is "white eye" or "cat's eye" (leukocoria).
Prognosis: In the developed world, retinoblastoma has one of the best cure rates of all childhood cancers (95-98%), with more than 90% of sufferers surviving into adulthood. In the UK, around 40 to 50 new cases are diagnosed each year. Good prognosis depends upon early presentation of the child in health facility. Late presentation is associated with a poor prognosis. Survivors of hereditary retinoblastoma have a higher risk of developing other cancers later in life.
Onset: Retinoblastoma is a type of eye cancer that typically affects young children, usually before the age of five. It can occur in one or both eyes and may be hereditary or non-hereditary. Early detection and treatment are crucial for preserving vision and preventing the spread of the cancer.
Prevalence: Retinoblastoma is a rare type of eye cancer that typically affects young children. The prevalence of retinoblastoma is approximately 1 in 15,000 to 1 in 20,000 live births worldwide.
Epidemiology: Retinoblastoma presents with cumulative lifetime incidence rate of one case of retinoblastoma per 18000 to 30000 live births worldwide. A higher incidence is noted in developing countries, which has been attributed to lower socioeconomic status and the presence of human papilloma virus sequences in the retinoblastoma tissue.Almost 80% of children with retinoblastoma are diagnosed before three years of age and diagnosis in children above six years of age is extremely rare. In the UK, bilateral cases usually present within 14 to 16 months, while diagnosis of unilateral cases peaks between 24 and 30 months.
Intractability: Retinoblastoma is a type of eye cancer that is typically not considered intractable, especially when detected early. Treatment options such as chemotherapy, radiation therapy, laser therapy, cryotherapy, and surgery can be effective in managing the disease and preserving vision. However, the prognosis can vary depending on the stage at diagnosis and whether or not the cancer has spread beyond the eye. Early intervention is crucial for a more favorable outcome.
Disease Severity: Retinoblastoma is a cancer that begins in the retina, most commonly affecting young children. Regarding disease severity, it can range from treatable with good prognosis when caught early, to life-threatening if it spreads beyond the eye. "nan" does not pertain to medical contexts related to disease severity.
Healthcare Professionals: Disease Ontology ID - DOID:768
Pathophysiology: Retinoblastoma is a malignant tumor that originates in the retinal cells of the eye, predominantly affecting young children. The pathophysiology involves the mutation of both alleles of the RB1 gene, located on chromosome 13. The RB1 gene normally functions as a tumor suppressor, and its inactivation leads to uncontrolled cell proliferation. The mutation can be hereditary (germline mutation) or can occur sporadically (somatic mutation). The loss of RB1 function disrupts the regulation of the cell cycle, causing retinal cells to grow uncontrollably and form tumors.
Carrier Status: Retinoblastoma is a type of eye cancer that primarily affects young children. It can be hereditary (genetic) or non-hereditary (sporadic).

- Carrier Status: In hereditary retinoblastoma, individuals carry a mutation in the RB1 gene. This can be detected through genetic testing. Carriers who possess one mutated copy of the RB1 gene have a high risk of developing retinoblastoma.

- NA/N: This term isn't directly related to retinoblastoma. If you need clarification on a specific aspect involving nanotechnology or other details, please specify.
Mechanism: Retinoblastoma is a rare type of eye cancer that typically develops in early childhood and arises from immature retinal cells.

**Mechanism:**
The primary mechanism underlying retinoblastoma involves mutations in the RB1 gene, which is crucial for regulating the cell cycle. The RB1 gene encodes the retinoblastoma protein (pRB), a tumor suppressor that controls the transition from the G1 to the S phase of the cell cycle by inhibiting the activity of E2F transcription factors. Mutations in the RB1 gene lead to loss of pRB function, resulting in uncontrolled cell proliferation.

**Molecular Mechanisms:**
1. **RB1 Gene Mutation:** The majority of retinoblastomas involve biallelic inactivation of the RB1 gene, meaning both alleles must be affected. This can occur through inherited mutations (germline mutations) or somatic mutations.

2. **Loss of Heterozygosity (LOH):** In cases where an individual inherits one mutant RB1 allele (germline), the second allele can be lost or mutated somatically, a phenomenon known as LOH, leading to tumor development.

3. **E2F Transcription Factor Deregulation:** Without functional pRB, E2F transcription factors are not properly regulated, leading to increased expression of genes required for DNA replication and cell cycle progression, driving the cells into continuous division and proliferation.

4. **Genomic Instability:** The lack of pRB function can lead to genomic instability, further genetic mutations, and chromosomal aberrations, contributing to tumor progression.

5. **Alternative Pathways:** While RB1 mutations are the primary cause, other genetic and epigenetic changes in retinoblastoma cells can also contribute to tumorigenesis, such as amplification of MYCN, a gene that can drive cell proliferation in the absence of RB1 mutations.

These molecular events collectively lead to the development of retinoblastoma, highlighting the critical role of the RB1 gene in retinal cell cycle control and tumor suppression.
Treatment: The priority of retinoblastoma treatment is to preserve the life of the child, then to preserve vision, and then to minimize complications or side effects of treatment. The exact course of treatment depends on the individual case and is decided by the ophthalmologist in discussion with the paediatric oncologist. Correct treatment also depends on the mutation type, whether it is a germline RB1 mutation, a sporadic RB1 mutation or MYCN amplification with functional RB1. Children with involvement of both eyes at diagnosis usually require multimodality therapy (chemotherapy, local therapies).
The various treatment modalities for retinoblastoma includes:
Enucleation of the eye – Most patients with unilateral disease present with advanced intraocular disease, so usually undergo enucleation, which results in a cure rate of 95%. In bilateral Rb, enucleation is usually reserved for eyes that have failed all known effective therapies or without useful vision.
External beam radiotherapy (EBRT) – The most common indication for EBRT is for the eye in a young child with bilateral retinoblastoma who has active or recurrent disease after completion of chemotherapy and local therapies. However, patients with hereditary disease who received EBRT therapy are reported to have a 35% risk of second cancers.
Brachytherapy involves the placement of a radioactive implant (plaque), usually on the sclera adjacent to the base of a tumor. It used as the primary treatment, or more frequently, in patients with small tumors or in those who had failed initial therapy including previous EBRT therapy.
Thermotherapy involves the application of heat directly to the tumor, usually in the form of infrared radiation. It is also used for small tumors.
Laser photocoagulation is recommended only for small posterior tumors. An argon or diode laser or a xenon arc is used to coagulate all the blood supply to the tumor.
Cryotherapy induces damage to the vascular endothelium with secondary thrombosis and infarction of the tumor tissue by rapidly freezing it. It may be used as primary therapy for small peripheral tumors or for small recurrent tumors previously treated with other methods.
Systemic chemotherapy has become forefront of treatment in the past decade, in the search for globe-preserving measures and to avoid the adverse effects of EBRT therapy. The common indications for chemotherapy for intraocular retinoblastoma include tumors that are large and that cannot be treated with local therapies alone in children with bilateral tumors. It is also used in patients with unilateral disease when the tumors are small, but cannot be controlled with local therapies alone.
Intra-arterial chemotherapy – Chemotherapeutic drugs are administered locally by a thin catheter threaded through the groin, through the aorta, and the neck, directly into the optic vessels.
Nanoparticulate chemotherapy – To reduce the adverse effects of systemic therapy, subconjuctival (local) injection of nanoparticle carriers containing chemotherapeutic agents (carboplatin) has been developed, which has shown promising results in the treatment of retinoblastoma in animal models without adverse effects.
Chemoreduction is a combined approach using chemotherapy to initially reduce the size of the tumor, and adjuvant focal treatments, such as transpupillary thermotherapy, to control the tumor.
Compassionate Use Treatment: For retinoblastoma, compassionate use treatments and experimental or off-label treatments can include:

1. **Intra-arterial Chemotherapy (IAC)**: Administering chemotherapy directly into the ophthalmic artery to target the tumor.

2. **Intravitreal Chemotherapy**: Injecting chemotherapy drugs directly into the vitreous humor of the eye, especially for vitreous seeds that are challenging to treat with other methods.

3. **Episcleral Plaque Brachytherapy**: A form of localized radiation treatment using a radioactive plaque placed on the sclera (the white part of the eye) near the tumor to deliver targeted radiation.

4. **Systemic Chemotherapy**: Although a standard treatment, it may be adapted for use in cases where the disease has spread or when other treatments are not suitable.

5. **Targeted Therapies**: Investigational drugs targeting specific molecular pathways involved in the growth of retinoblastoma cells. Currently under research and may only be available through clinical trials.

6. **Genetic Therapies**: Experimental approaches aiming to correct or mitigate the genetic defects causing retinoblastoma, still primarily in the research phase.

Patients considering these options should consult with their oncologist and inquire about availability and eligibility for clinical trials or special access programs.
Lifestyle Recommendations: Lifestyle recommendations for retinoblastoma are primarily focused on managing the condition and promoting overall well-being. Key considerations include:

1. **Regular Follow-ups**: Ensure consistent appointments with an ophthalmologist and oncologist to monitor the disease progression and manage any complications.

2. **Healthy Diet**: Maintain a nutritious diet to support overall health and immune function, which can be crucial during and after treatment.

3. **Protective Eyewear**: If vision is affected, wearing protective eyewear can prevent injuries and support visual health.

4. **Emotional Support**: Psychological counseling and support groups can help the child and family cope with the emotional impact of the diagnosis and treatment.

5. **Physical Activity**: Encourage age-appropriate physical activity to enhance physical and mental health, while considering any limitations due to treatment side effects.

6. **Sun Protection**: Protect the eyes from UV radiation with appropriate sunglasses and brimmed hats when outdoors.

Adhering to these recommendations can help manage the condition and improve quality of life for children with retinoblastoma.
Medication: Retinoblastoma is a rare form of eye cancer that primarily affects young children. Medications used in its treatment include:

1. **Systemic Chemotherapy:**
- Carboplatin
- Etoposide
- Vincristine

2. **Intra-arterial Chemotherapy:**
- Melphalan

3. **Intravitreal Chemotherapy:**
- Melphalan
- Topotecan

Nanotechnology is being investigated for its potential in retinoblastoma treatment, including targeted drug delivery systems that can improve the efficacy and reduce side effects of chemotherapy.
Repurposable Drugs: In the context of retinoblastoma, repurposable drugs being studied include:

1. **Melphalan**: Traditionally used as a chemotherapy agent for multiple myeloma, it has been repurposed for intra-arterial chemotherapy in retinoblastoma.
2. **Topotecan**: Originally used for ovarian cancer and small cell lung cancer, it has shown efficacy in retinoblastoma as an intra-arterial or intravitreal chemotherapeutic agent.
3. **Carboplatin**: Although mainly used for ovarian and lung cancers, its intravitreal and periocular administration has been explored for retinoblastoma treatment.

These drugs are considered for repurposing due to their ability to target cancer cells and their manageable safety profiles.
Metabolites: Retinoblastoma is a type of eye cancer that begins in the retina. Metabolites associated with retinoblastoma can include altered levels of lactate, choline-containing compounds, and lipids, reflecting changes in cellular metabolism and proliferation. Increased lactate is often due to the Warburg effect, where cancer cells preferentially use glycolysis for energy production even in the presence of oxygen.
Nutraceuticals: For retinoblastoma, there is currently no strong evidence to suggest that nutraceuticals (dietary supplements, vitamins, or other food-derived products) play a role in its prevention or treatment. Nutraceuticals should not replace standard treatments such as chemotherapy, radiation therapy, or surgical interventions. Always consult a healthcare provider for an appropriate treatment plan for retinoblastoma.
Peptides: Retinoblastoma is a malignant tumor of the retina, primarily affecting young children. It originates from retinal cells and can be hereditary or non-hereditary. Detection often involves identifying a white pupillary reflex or leukocoria.

**Peptides:**
Research in retinoblastoma includes exploring peptide-based therapies. These peptides can target specific cancer pathways or microenvironments, potentially offering therapeutic benefits. Examples include peptide vaccines or inhibitors designed to disrupt critical protein-protein interactions involved in tumor growth and survival.

**Nanotechnology:**
Nanotechnology is being investigated for its potential in targeted drug delivery for retinoblastoma. Nanoparticles can be engineered to deliver drugs directly to the tumor site, minimizing side effects and enhancing treatment efficacy. Techniques such as using liposomes, dendrimers, and other nanocarriers are being studied to improve drug solubility, stability, and controlled release.