Beckwith-wiedemann Syndrome
Disease Details
Family Health Simplified
- Description
- Beckwith-Wiedemann syndrome is a genetic disorder characterized by overgrowth of various body parts and an increased risk of developing certain tumors during childhood.
- Type
- Beckwith-Wiedemann syndrome is primarily a genetic disorder, with its most common type being caused by abnormal regulation of imprinted genes in the 11p15.5 region of chromosome 11. The type of genetic transmission is usually sporadic, but it can also follow an autosomal dominant pattern with variable expressivity and incomplete penetrance.
- Signs And Symptoms
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Beckwith-Wiedemann Syndrome (BWS) is an overgrowth disorder typically present at birth. The primary signs and symptoms include:
1. **Macroglossia**: An unusually large tongue.
2. **Macrosomia**: Larger-than-average size and weight at birth.
3. **Abdominal Wall Defects**: Such as omphalocele or umbilical hernia.
4. **Hemihyperplasia**: One side of the body grows larger than the other.
5. **Neonatal Hypoglycemia**: Low blood sugar in newborns.
6. **Ear Anomalies**: Creases or pits in the ear.
7. **Visceromegaly**: Enlargement of internal organs, including liver, spleen, and kidneys.
8. **Increased Risk of Tumors**: Particularly Wilms' tumor and hepatoblastoma in childhood.
Regular monitoring and early intervention are crucial for managing symptoms and associated risks. - Prognosis
- In general, the prognosis is very good. Children with BWS usually do very well and grow up to become the heights expected based on their parents' heights. While they are at increased risk of childhood cancer, most of them do not develop the disease, and the vast majority of the children who do can be treated successfully.Children with BWS for the most part had no significant delays when compared to their siblings. However, some of them do have speech problems that could be related to macroglossia or hearing loss.Advances in treating neonatal complications and premature infants in the last twenty years have significantly improved the true infant mortality rate associated with BWS. In a review of pregnancies that resulted in 304 children with BWS, no neonatal deaths were reported. This is compared to a previously reported mortality rate of 20%. The data from the former study was derived from a BWS registry, a database that may be slightly biased towards involving living children; however, death was not an exclusion criterion to join the registry. This suggests that while infants with BWS are likely to have a higher than normal infant mortality risk, it may not be as high as 20%.
- Onset
- Beckwith-Wiedemann syndrome is typically present at birth (congenital), and its onset is usually evident in infancy or early childhood. Signs and symptoms can vary but often include overgrowth, abdominal wall defects, and an increased risk of developing certain childhood cancers.
- Prevalence
- Beckwith-Wiedemann syndrome (BWS) is a genetic disorder with a prevalence estimated to be about 1 in 13,700 newborns.
- Epidemiology
- Beckwith–Wiedemann syndrome has an estimated incidence of one in 13,700; about 300 children with BWS are born each year in the United States. The exact incidence of BWS is unknown because of the marked variability in the syndrome's presentation and difficulties with diagnosis. The number of reported infants born with BWS is most likely low because many are born with BWS, but have clinical features that are less prominent and therefore missed. BWS has been documented in a variety of ethnic groups and occurs equally in males and females.Children conceived through in vitro fertilization have a three to fourfold increased chance of developing Beckwith–Wiedemann syndrome. It is thought that this is due to genes being turned on or off by the IVF procedures.
- Intractability
- Beckwith-Wiedemann Syndrome (BWS) is not considered intractable. It is a congenital growth disorder with a variable range of symptoms and severity. While there is no cure, BWS can often be managed with appropriate medical care. Treatments may include surgical interventions, monitoring for tumor development, and addressing any associated complications such as hypoglycemia. Early diagnosis and ongoing medical supervision can significantly improve outcomes for those with the disorder.
- Disease Severity
- Beckwith-Wiedemann syndrome (BWS) exhibits variable severity. It can range from mild to severe, depending on the specific manifestations and complications in each individual. Symptoms may include overgrowth, abdominal wall defects, organomegaly, hypoglycemia, and an increased risk of certain cancers, such as Wilms tumor and hepatoblastoma. Regular monitoring and management are essential to address and mitigate potential complications.
- Healthcare Professionals
- Disease Ontology ID - DOID:5572
- Pathophysiology
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Beckwith-Wiedemann syndrome (BWS) is a genetic overgrowth disorder that affects various parts of the body. Its pathophysiology primarily involves abnormalities in the regulation of gene expression in the imprinted region of chromosome 11p15.5. Genes in this region, including IGF2 (insulin-like growth factor 2) and CDKN1C (cyclin-dependent kinase inhibitor 1C), play crucial roles in growth regulation and cellular proliferation.
In BWS, disruptions can occur through different mechanisms:
1. **Loss of Imprinting (LOI)**: This leads to the activation of both paternal and maternal alleles of growth-promoting genes (like IGF2) instead of the usual single active copy.
2. **Paternal Uniparental Disomy (UPD)**: Both copies of this chromosome region are inherited from the father, leading to overexpression of paternally expressed genes and lack of maternally expressed genes.
3. **Mutations**: Changes in the CDKN1C gene can disrupt growth inhibition, leading to unregulated cellular proliferation.
4. **Hypermethylation**: Increased methylation of certain genomic control regions further disrupts proper gene function, contributing to overgrowth and tumor predisposition.
These genetic and epigenetic changes result in the clinical manifestations of BWS, which include macrosomia (excessive birth weight), macroglossia (enlarged tongue), abdominal wall defects, hemihyperplasia (asymmetrical overgrowth), and an increased risk for developing embryonal tumors, such as Wilms' tumor. - Carrier Status
- Beckwith-Wiedemann syndrome is not typically associated with a traditional carrier status seen in many genetic disorders. It is mostly caused by genetic and epigenetic changes affecting the imprinted regions on chromosome 11, particularly in the 11p15.5 region. The disorder can result from various genetic mechanisms, such as loss of methylation, gain of methylation, paternal uniparental disomy, or mutations in the CDKN1C gene. Therefore, it does not follow a simple Mendelian inheritance pattern, and the concept of carrier status does not straightforwardly apply.
- Mechanism
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Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder associated with various genetic and epigenetic changes.
**Mechanism:**
- **Genetic Imprinting Disorder:** BWS is often caused by abnormalities in imprinted genes on chromosome 11p15.5. Imprinted genes are expressed in a parent-of-origin-specific manner.
- **Overgrowth and Tumor Risk:** The disorder can lead to overgrowth of body parts and an increased risk of childhood tumors, particularly Wilms tumor and hepatoblastoma.
**Molecular Mechanisms:**
1. **Loss of Imprinting (LOI):** The most common molecular mechanism involves loss of imprinting at the IGF2 (Insulin-like Growth Factor 2) gene, leading to biallelic expression. Normally, IGF2 is only expressed from the paternal allele.
2. **H19 Gene:** Hypomethylation of the H19 gene's imprinting control region (ICR1) can also result in increased IGF2 expression, contributing to overgrowth.
3. **CDKN1C Mutations:** Mutations or epigenetic alterations in CDKN1C, a gene that encodes a cell cycle inhibitor, can lead to uncontrolled cell division.
4. **KCNQ1OT1:** Hypermethylation of KCNQ1OT1 (ICR2) results in silencing of tumor suppressor genes in this region, contributing further to the risk of developing tumors.
These molecular disruptions collectively contribute to the phenotypic manifestations of BWS. - Treatment
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Treatment for Beckwith-Wiedemann syndrome (BWS) focuses on managing its various symptoms and associated complications. This may include:
1. **Monitoring for tumors:** Regular screening through abdominal ultrasounds and blood tests (alpha-fetoprotein levels) to detect early signs of tumor development, especially Wilms tumor and hepatoblastoma.
2. **Surgical interventions:** Surgery may be required to correct certain congenital abnormalities like omphalocele (abdominal wall defect) or to address macroglossia (enlarged tongue) for improved feeding, speech, and breathing.
3. **Orthopedic management:** Management of limb and skeletal abnormalities such as hemihyperplasia (asymmetrical overgrowth of one side of the body) may require orthopedic follow-up and possibly surgical intervention.
4. **Developmental support:** Early intervention programs and regular developmental assessments to address any delays or cognitive issues.
5. **Regular monitoring and check-ups:** Routine follow-ups with a multidisciplinary team including pediatricians, geneticists, and other specialists as required to monitor growth and overall development.
In addition to these, specific treatments are tailored to the individual needs of the patient based on their specific symptoms and complications. - Compassionate Use Treatment
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Beckwith-Wiedemann Syndrome (BWS) is a genetic disorder characterized by overgrowth and an increased risk of developing childhood cancers. There is currently no specific compassionate use treatment, off-label, or experimental treatment designated solely for BWS. Management typically focuses on addressing the individual symptoms and complications associated with the syndrome, such as:
1. **Monitoring and Screening for Cancer**: Regular abdominal ultrasounds and blood tests (e.g., alpha-fetoprotein levels) to detect early signs of tumors like Wilms' tumor or hepatoblastoma.
2. **Surgical Intervention**: Surgery may be required to correct related anomalies, such as abdominal wall defects, macroglossia (enlarged tongue), or tumors.
3. **Growth Management**: Monitoring and managing growth abnormalities, potentially using endocrinological treatments if necessary.
Individualized care plans, based on the patient's specific presentation of the syndrome, are essential. Collaborative care involving pediatricians, geneticists, oncologists, and other specialists is often necessary for comprehensive management. Researchers continue to explore potential treatments, but no specific experimental therapies are established for BWS at this time. - Lifestyle Recommendations
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Beckwith-Wiedemann syndrome (BWS) is a genetic overgrowth disorder that can involve an increased risk of childhood cancers and various congenital abnormalities. Important lifestyle recommendations for individuals with BWS generally focus on monitoring and healthcare management:
1. **Regular Medical Check-ups**: Schedule routine visits with healthcare providers to monitor growth patterns and developmental milestones. This helps in early detection and management of potential complications.
2. **Cancer Surveillance**: Due to an increased risk of embryonal tumors such as Wilms tumor and hepatoblastoma, regular abdominal ultrasounds and alpha-fetoprotein (AFP) blood tests are often recommended until around age 8.
3. **Healthy Diet**: Ensure a balanced diet to support overall health and development. Nutritional guidance may be necessary, especially if there are feeding issues or gastrointestinal concerns.
4. **Physical Activity**: Encourage age-appropriate physical activity to support physical development and prevent obesity, a common issue in BWS.
5. **Growth Monitoring**: Regularly measure and record height, weight, and head circumference to track growth patterns and identify any concerns early.
6. **Dental Care**: Early and regular dental evaluations are advised as children with BWS may have an increased risk of dental issues due to macroglossia (enlarged tongue).
7. **Developmental Support**: Engage with early intervention programs if developmental delays or learning difficulties are identified. Support from occupational, physical, or speech therapists can be beneficial.
8. **Parental Education**: Educate parents or caregivers about the signs and symptoms of potential complications and the importance of adherence to screening protocols.
9. **Psychosocial Support**: Providing emotional and psychological support for the child and family can help them cope with the challenges of the syndrome.
10. **Protective Gear for Sports**: If the child is involved in sports, ensure that they wear appropriate protective gear to prevent injuries, especially if there are any hypo- or hyper-coagulability concerns associated with the syndrome.
Regular coordination with a multidisciplinary team of healthcare providers can optimize the management and improve the quality of life for individuals with Beckwith-Wiedemann syndrome. - Medication
- There is no specific medication for Beckwith-Wiedemann Syndrome (BWS). Management typically involves regular monitoring and supportive treatments tailored to individual symptoms, which may include addressing overgrowth concerns, managing hypoglycemia, and monitoring for tumor development. Treatment often involves a multidisciplinary team including pediatricians, endocrinologists, and geneticists.
- Repurposable Drugs
- There are currently no specific drugs approved for the treatment of Beckwith-Wiedemann syndrome (BWS). Management of BWS typically focuses on addressing individual symptoms and complications, such as macroglossia, omphalocele, and increased risk of certain cancers. Supportive interventions might include surgery for physical anomalies and regular cancer screening. Researchers continue to explore potential therapeutic options, but no repurposable drugs have been conclusively identified for BWS at this time.
- Metabolites
- Metabolites associated with Beckwith-Wiedemann syndrome (BWS) are not well-characterized due to the syndrome's complex nature involving multiple genes responsible for growth regulation and cell proliferation. BWS can lead to various metabolic abnormalities, but specific consistent metabolite changes are not yet definitively identified. Further research is needed to elaborate on the metabolic profile of individuals with BWS.
- Nutraceuticals
- There are no specific nutraceuticals recommended or proven to treat or manage Beckwith-Wiedemann Syndrome (BWS). This genetic condition is characterized by overgrowth and an increased risk of childhood cancers, among other features. Management typically involves routine screenings and medical supervision to monitor and address potential complications. Always consult healthcare professionals for personalized medical advice.
- Peptides
- Beckwith-Wiedemann Syndrome (BWS) is primarily a genetic condition associated with overgrowth and an increased risk of childhood cancers. There is no established treatment involving peptides or nanotechnology specifically for managing BWS. Treatment typically involves monitoring and managing symptoms like overgrowth, abdominal wall defects, and risk of tumors, through regular screenings and surgical interventions as needed.