Beckwith-Wiedemann Syndrome (BWS) is a rare genetic disorder characterized by various features that affect growth and development. It was named after the two physicians who independently described the syndrome in the 1960s: Dr. John Bruce Beckwith and Dr. Hans-Rudolf Wiedemann.
BWS is typically present at birth and is associated with abnormalities in the regulation of genes involved in growth and development. It is caused by genetic and epigenetic alterations that affect the expression of certain genes on chromosome 11.
Epidemiology
Beckwith-Wiedemann Syndrome (BWS) is considered a rare disorder, but its exact prevalence is difficult to determine due to its variable clinical presentation and underdiagnosis. The reported prevalence of BWS ranges from approximately 1 in 10,000 to 1 in 15,000 live births. BWS affects both males and females and has been reported in various ethnic groups and geographical regions worldwide.
There is no specific geographic or ethnic predisposition for the syndrome. Certain factors have been associated with an increased risk of BWS, including advanced maternal age (mothers older than 35 years), multiple pregnancies (twins, triplets, etc.), and assisted reproductive technologies (such as in vitro fertilization). These factors may be associated with an increased frequency of epigenetic changes that contribute to the development of BWS.
Anatomy
Pathophysiology
Beckwith-Wiedemann Syndrome (BWS) is a complex genetic disorder characterized by alterations in the regulation of gene expression on chromosome 11. The pathophysiology of BWS involves genetic and epigenetic changes that disrupt the normal growth and development of various tissues and organs.
The majority of BWS cases (approximately 85%) are sporadic, meaning they occur randomly and are not inherited from parents. These cases are usually associated with abnormalities in a region on chromosome 11 called 11p15.5. This region contains several imprinted genes that play a role in growth regulation and development.
Imprinting refers to the process by which certain genes are “marked” or “stamped” with instructions from either the mother or father. In BWS, there is disruption in the normal imprinting patterns of genes in the 11p15.5 region. This disruption can occur through different mechanisms, including:
Loss of Imprinting: In some cases of BWS, there is a loss of imprinting (LOI) at specific genes, such as insulin-like growth factor 2 (IGF2) and H19. LOI leads to the biallelic expression (expression from both the maternal and paternal alleles) of these genes, which can result in increased cell growth and proliferation.
Abnormal DNA Methylation: DNA methylation is an epigenetic modification that can influence gene expression. In BWS, there can be abnormal DNA methylation patterns in the 11p15.5 region, affecting genes such as IGF2, H19, and KCNQ1OT1. These abnormalities in DNA methylation can disrupt the normal regulation of gene expression and contribute to the characteristic features of BWS.
Chromosomal Abnormalities: In a small percentage of BWS cases, there may be chromosomal abnormalities involving chromosome 11, such as duplications or translocations. These structural alterations can disrupt the normal functioning of genes in the 11p15.5 region, leading to BWS symptoms.
The altered gene expression patterns in BWS can affect various tissues and organs, resulting in the characteristic clinical features of the syndrome. These features can include overgrowth, macroglossia (enlarged tongue), abdominal wall defects, organomegaly (enlarged organs), neonatal hypoglycemia (low blood sugar), and an increased risk of certain tumors, such as Wilms tumor and hepatoblastoma. The specific mechanisms by which the genetic and epigenetic alterations lead to the clinical manifestations of BWS are still not fully understood.
Further research is needed to elucidate the precise pathophysiological mechanisms and the interplay between the disrupted genes and signaling pathways involved in BWS. Understanding the underlying pathophysiology of BWS is important for improved diagnosis, genetic counseling, and the development of targeted therapies or interventions to manage the symptoms and complications associated with the syndrome.
Etiology
The etiology of Beckwith-Wiedemann Syndrome (BWS) involves genetic and epigenetic factors that lead to alterations in the regulation of gene expression on chromosome 11. The majority of BWS cases (approximately 85%) are sporadic, meaning they occur randomly and are not inherited from parents. However, around 10-15% of cases are inherited in an autosomal dominant manner, meaning they can be passed from an affected parent to their children.
Here are the key factors contributing to the etiology of BWS:
Genetic Abnormalities: The most common genetic abnormality associated with BWS involves alterations in a region on chromosome 11 called 11p15.5. This region contains several imprinted genes that play a role in growth regulation and development. Imprinting refers to the process by which certain genes are marked or stamped with instructions from either the mother or father. In BWS, there can be disruptions in the normal imprinting patterns of genes in the 11p15.5 region. This disruption can occur through different mechanisms, including loss of imprinting (LOI) and abnormal DNA methylation.
Loss of Imprinting (LOI): Loss of imprinting occurs when there is a disruption in the normal silencing or activation of specific genes from one parent. In BWS, LOI can lead to biallelic (both maternal and paternal) expression of certain genes, such as insulin-like growth factor 2 (IGF2), which can result in increased cell growth and proliferation.
Abnormal DNA Methylation: DNA methylation is an epigenetic modification that can influence gene expression. In BWS, there can be abnormal DNA methylation patterns in the 11p15.5 region, affecting genes such as IGF2, H19, and KCNQ1OT1. These abnormalities in DNA methylation can disrupt the normal regulation of gene expression and contribute to the characteristic features of BWS.
Chromosomal Abnormalities: In a small percentage of BWS cases, there may be chromosomal abnormalities involving chromosome 11, such as duplications or translocations. These structural alterations can disrupt the normal functioning of genes in the 11p15.5 region, leading to BWS symptoms.
Genetics
Prognostic Factors
The prognosis of Beckwith-Wiedemann Syndrome (BWS) can vary widely depending on the specific features and complications present in each individual. While some individuals with BWS have a relatively mild course and lead healthy lives, others may experience more severe manifestations and face greater challenges. Here are some factors that can influence the prognosis of BWS:
Tumor Risk: The most significant factor impacting the prognosis of BWS is the increased risk of developing tumors, particularly Wilms tumor (kidney cancer) and hepatoblastoma (liver cancer). The prognosis for tumor development depends on various factors, including the size, stage, and response to treatment. Early detection through regular tumor surveillance and prompt intervention can improve outcomes and prognosis.
Organomegaly: Enlargement of organs, such as the liver, kidneys, or adrenal glands, may occur in individuals with BWS. The degree of organomegaly and associated complications can vary. In some cases, organomegaly may resolve or remain stable over time, while in others, it may lead to functional impairment and require ongoing management.
Macrosomia and Growth: Infants with BWS often present with macrosomia (excessive body size) and overgrowth. While overgrowth tends to be most prominent during the first few years of life, it may persist into childhood. The prognosis for growth largely depends on the severity of macrosomia and whether it leads to associated complications such as obesity or orthopedic issues.
Neurodevelopmental Challenges: Some individuals with BWS may experience neurodevelopmental challenges, including speech and language delays, cognitive impairments, or behavioral issues. The prognosis for neurodevelopmental outcomes can vary, and early intervention with appropriate therapies and support can help optimize developmental potential.
Surgical Interventions: The need for surgical interventions, such as repair of abdominal wall defects or orthopedic procedures, can influence the prognosis. The outcomes of surgical procedures depend on the specific indications, timing, and the expertise of the surgical team.
Clinical History
Clinical history
The clinical history of Beckwith-Wiedemann Syndrome (BWS) can vary among affected individuals, as the syndrome is characterized by a range of features. Here are some key aspects of the clinical history associated with BWS:
Prenatal History: In some cases, BWS may be suspected prenatally due to findings on ultrasound or other prenatal imaging. Features such as macrosomia (excessive fetal growth), polyhydramnios (excess amniotic fluid), and abdominal wall defects, such as omphalocele or umbilical hernia, may be detected during prenatal evaluation.
Macrosomia: Macrosomia refers to excessive fetal or postnatal growth. Infants with BWS often have a larger birth weight and length compared to their peers. The degree of macrosomia can vary, ranging from mild to severe. Overgrowth is most prominent during the first few years of life, but it may persist into childhood.
Macroglossia: Macroglossia, or enlargement of the tongue, is a common feature of BWS. It can be present at birth or become more apparent during infancy. Macroglossia can cause feeding difficulties, speech delays, and dental issues.
Abdominal Wall Defects: Approximately 70-80% of individuals with BWS have abdominal wall defects. These defects can include umbilical hernia (a protrusion of abdominal contents through the belly button), omphalocele (abdominal organs protruding outside the body through the umbilical cord), or diastasis recti (separation of the abdominal muscles).
Organomegaly: Enlargement of organs, such as the liver, kidneys, or adrenal glands, may occur in individuals with BWS. The degree of organomegaly can vary, and it may be detected during physical examination or through imaging studies.
Neonatal Hypoglycemia: Neonatal hypoglycemia, or low blood sugar levels shortly after birth, can occur in infants with BWS. It is usually transient but may require monitoring and management to maintain stable blood sugar levels.
Hemihypertrophy: Hemihypertrophy refers to asymmetric overgrowth of one side of the body. It may manifest as one limb or one side of the body being larger than the other. Hemihypertrophy can be present in some individuals with BWS.
Increased Tumor Risk: Individuals with BWS have an increased risk of developing certain tumors, particularly Wilms tumor (a type of kidney cancer) and hepatoblastoma (a type of liver cancer). Regular tumor screening and surveillance are recommended in affected individuals.
Physical Examination
Physical examination
The physical examination of an individual with Beckwith-Wiedemann Syndrome (BWS) aims to identify the characteristic clinical features associated with the syndrome. Here are the key aspects that may be assessed during the physical examination:
General Appearance: The overall appearance of individuals with BWS can vary, but they may exhibit features of macrosomia (excessive body size) and overgrowth. The assessment includes observing the height, weight, and overall body proportions.
Facial Features: While BWS does not have specific facial characteristics, some individuals may have subtle facial differences. These can include a large or prominent forehead, wide-set eyes, and a round face. However, it’s important to note that the facial appearance in BWS can be variable and not present in all cases.
Macroglossia: Macroglossia, or an enlarged tongue, is a common finding in BWS. During the examination, the size and appearance of the tongue are assessed. Macroglossia can cause the tongue to protrude beyond the oral cavity and may contribute to feeding difficulties or speech delays.
Abdominal Wall Defects: Abdominal examination is performed to assess for any abdominal wall defects that are commonly associated with BWS. These may include umbilical hernia (protrusion of abdominal contents through the belly button), omphalocele (protrusion of abdominal organs outside the body through the umbilical cord), or diastasis recti (separation of the abdominal muscles).
Organomegaly: The size and consistency of abdominal organs, such as the liver, kidneys, and adrenal glands, may be assessed during the examination. Enlargement or abnormalities in the size or shape of these organs can indicate organomegaly, which is commonly seen in individuals with BWS.
Limb and Body Asymmetry: Asymmetrical overgrowth, known as hemihypertrophy, can be present in individuals with BWS. During the examination, the limbs and body are observed for any differences in size or length between the left and right sides.
Skin Abnormalities: Certain skin findings, such as birthmarks or nevi (pigmented skin lesions), may be observed in individuals with BWS. These skin abnormalities are not specific to BWS but can be present in some cases.
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Differential diagnosis
When evaluating a patient with suspected Beckwith-Wiedemann Syndrome (BWS), it is important to consider other conditions that may present with similar features. The differential diagnosis of BWS includes:
Simpson-Golabi-Behmel Syndrome (SGBS): SGBS is a genetic disorder that shares some clinical features with BWS, such as macrosomia (large body size), macroglossia (enlarged tongue), and organomegaly. However, SGBS is associated with distinctive facial features, skeletal abnormalities, and an increased risk of certain tumors. Genetic testing can help differentiate between BWS and SGBS.
Silver-Russell Syndrome (SRS): SRS is a genetic disorder characterized by growth restriction, asymmetric body size, and distinctive facial features. Although there can be some overlapping features with BWS, the absence of macrosomia and the presence of growth restriction and asymmetry are more typical of SRS.
Perlman Syndrome: Perlman syndrome is a rare genetic disorder characterized by macrosomia, visceromegaly (enlarged abdominal organs), polyhydramnios (excessive amniotic fluid), and distinctive facial features. Renal abnormalities and an increased risk of Wilms tumor are also seen in Perlman syndrome. Genetic testing can differentiate between Perlman syndrome and BWS.
Overgrowth Syndromes: There are other genetic overgrowth syndromes that can present with macrosomia and features similar to BWS, such as Sotos syndrome, Weaver syndrome, and Marshall-Smith syndrome. Each of these syndromes has specific clinical features that can help distinguish them from BWS.
Isolated Hemihypertrophy: Hemihypertrophy, or asymmetric overgrowth of one side of the body, can be seen in BWS. However, isolated hemihypertrophy without other features of BWS is a separate condition and should be considered in the differential diagnosis.
Other Genetic Syndromes: There are several other genetic syndromes that may have overlapping features with BWS, such as Prader-Willi syndrome, Angelman syndrome, and Russell-Silver syndrome. Genetic testing and a careful evaluation of clinical features are necessary to differentiate these syndromes from BWS.
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
The treatment of Beckwith-Wiedemann Syndrome (BWS) is primarily focused on managing the specific symptoms and associated complications that may arise. The approach to treatment involves a multidisciplinary team of healthcare professionals who work together to provide comprehensive care. Here are some key aspects of the treatment for BWS:
Management of Hypoglycemia: Neonatal hypoglycemia, or low blood sugar levels shortly after birth, is a common concern in infants with BWS. It may require careful monitoring and management to maintain stable blood sugar levels. This can involve frequent feedings, glucose monitoring, and in some cases, intravenous glucose administration.
Feeding Support: Macroglossia (enlarged tongue) and other oral motor difficulties associated with BWS can lead to feeding challenges. Support from a pediatric feeding specialist, such as a speech-language pathologist or occupational therapist, may be beneficial in optimizing feeding techniques and ensuring adequate nutrition.
Surgical Intervention: Abdominal wall defects, such as umbilical hernia or omphalocele, may require surgical repair. The timing and necessity of surgery depend on the severity and clinical presentation of the specific defect.
Tumor Surveillance: Individuals with BWS have an increased risk of developing certain tumors, most notably Wilms tumor (kidney cancer) and hepatoblastoma (liver cancer). Regular tumor screening and surveillance protocols, including imaging studies and laboratory tests, are recommended to detect and manage tumors at an early stage.
Orthopedic Management: Hemihypertrophy, or asymmetric overgrowth of one side of the body, may require orthopedic assessment and management. This can involve monitoring the musculoskeletal system, addressing limb length discrepancies, and managing any associated orthopedic conditions.
Dental Care: Macroglossia and other oral features in BWS can contribute to dental problems, such as malocclusion and overcrowding of teeth. Regular dental examinations and appropriate dental interventions, including orthodontic treatment, may be necessary to maintain oral health.
Psychosocial Support: BWS can have a significant impact on individuals and families, both physically and emotionally. Psychosocial support, including counseling, support groups, and access to resources, can help address the emotional and psychological aspects of living with BWS.
Beckwith-Wiedemann Syndrome (BWS) is a rare genetic disorder characterized by various features that affect growth and development. It was named after the two physicians who independently described the syndrome in the 1960s: Dr. John Bruce Beckwith and Dr. Hans-Rudolf Wiedemann.
BWS is typically present at birth and is associated with abnormalities in the regulation of genes involved in growth and development. It is caused by genetic and epigenetic alterations that affect the expression of certain genes on chromosome 11.
Beckwith-Wiedemann Syndrome (BWS) is considered a rare disorder, but its exact prevalence is difficult to determine due to its variable clinical presentation and underdiagnosis. The reported prevalence of BWS ranges from approximately 1 in 10,000 to 1 in 15,000 live births. BWS affects both males and females and has been reported in various ethnic groups and geographical regions worldwide.
There is no specific geographic or ethnic predisposition for the syndrome. Certain factors have been associated with an increased risk of BWS, including advanced maternal age (mothers older than 35 years), multiple pregnancies (twins, triplets, etc.), and assisted reproductive technologies (such as in vitro fertilization). These factors may be associated with an increased frequency of epigenetic changes that contribute to the development of BWS.
Beckwith-Wiedemann Syndrome (BWS) is a complex genetic disorder characterized by alterations in the regulation of gene expression on chromosome 11. The pathophysiology of BWS involves genetic and epigenetic changes that disrupt the normal growth and development of various tissues and organs.
The majority of BWS cases (approximately 85%) are sporadic, meaning they occur randomly and are not inherited from parents. These cases are usually associated with abnormalities in a region on chromosome 11 called 11p15.5. This region contains several imprinted genes that play a role in growth regulation and development.
Imprinting refers to the process by which certain genes are “marked” or “stamped” with instructions from either the mother or father. In BWS, there is disruption in the normal imprinting patterns of genes in the 11p15.5 region. This disruption can occur through different mechanisms, including:
Loss of Imprinting: In some cases of BWS, there is a loss of imprinting (LOI) at specific genes, such as insulin-like growth factor 2 (IGF2) and H19. LOI leads to the biallelic expression (expression from both the maternal and paternal alleles) of these genes, which can result in increased cell growth and proliferation.
Abnormal DNA Methylation: DNA methylation is an epigenetic modification that can influence gene expression. In BWS, there can be abnormal DNA methylation patterns in the 11p15.5 region, affecting genes such as IGF2, H19, and KCNQ1OT1. These abnormalities in DNA methylation can disrupt the normal regulation of gene expression and contribute to the characteristic features of BWS.
Chromosomal Abnormalities: In a small percentage of BWS cases, there may be chromosomal abnormalities involving chromosome 11, such as duplications or translocations. These structural alterations can disrupt the normal functioning of genes in the 11p15.5 region, leading to BWS symptoms.
The altered gene expression patterns in BWS can affect various tissues and organs, resulting in the characteristic clinical features of the syndrome. These features can include overgrowth, macroglossia (enlarged tongue), abdominal wall defects, organomegaly (enlarged organs), neonatal hypoglycemia (low blood sugar), and an increased risk of certain tumors, such as Wilms tumor and hepatoblastoma. The specific mechanisms by which the genetic and epigenetic alterations lead to the clinical manifestations of BWS are still not fully understood.
Further research is needed to elucidate the precise pathophysiological mechanisms and the interplay between the disrupted genes and signaling pathways involved in BWS. Understanding the underlying pathophysiology of BWS is important for improved diagnosis, genetic counseling, and the development of targeted therapies or interventions to manage the symptoms and complications associated with the syndrome.
The etiology of Beckwith-Wiedemann Syndrome (BWS) involves genetic and epigenetic factors that lead to alterations in the regulation of gene expression on chromosome 11. The majority of BWS cases (approximately 85%) are sporadic, meaning they occur randomly and are not inherited from parents. However, around 10-15% of cases are inherited in an autosomal dominant manner, meaning they can be passed from an affected parent to their children.
Here are the key factors contributing to the etiology of BWS:
Genetic Abnormalities: The most common genetic abnormality associated with BWS involves alterations in a region on chromosome 11 called 11p15.5. This region contains several imprinted genes that play a role in growth regulation and development. Imprinting refers to the process by which certain genes are marked or stamped with instructions from either the mother or father. In BWS, there can be disruptions in the normal imprinting patterns of genes in the 11p15.5 region. This disruption can occur through different mechanisms, including loss of imprinting (LOI) and abnormal DNA methylation.
Loss of Imprinting (LOI): Loss of imprinting occurs when there is a disruption in the normal silencing or activation of specific genes from one parent. In BWS, LOI can lead to biallelic (both maternal and paternal) expression of certain genes, such as insulin-like growth factor 2 (IGF2), which can result in increased cell growth and proliferation.
Abnormal DNA Methylation: DNA methylation is an epigenetic modification that can influence gene expression. In BWS, there can be abnormal DNA methylation patterns in the 11p15.5 region, affecting genes such as IGF2, H19, and KCNQ1OT1. These abnormalities in DNA methylation can disrupt the normal regulation of gene expression and contribute to the characteristic features of BWS.
Chromosomal Abnormalities: In a small percentage of BWS cases, there may be chromosomal abnormalities involving chromosome 11, such as duplications or translocations. These structural alterations can disrupt the normal functioning of genes in the 11p15.5 region, leading to BWS symptoms.
The prognosis of Beckwith-Wiedemann Syndrome (BWS) can vary widely depending on the specific features and complications present in each individual. While some individuals with BWS have a relatively mild course and lead healthy lives, others may experience more severe manifestations and face greater challenges. Here are some factors that can influence the prognosis of BWS:
Tumor Risk: The most significant factor impacting the prognosis of BWS is the increased risk of developing tumors, particularly Wilms tumor (kidney cancer) and hepatoblastoma (liver cancer). The prognosis for tumor development depends on various factors, including the size, stage, and response to treatment. Early detection through regular tumor surveillance and prompt intervention can improve outcomes and prognosis.
Organomegaly: Enlargement of organs, such as the liver, kidneys, or adrenal glands, may occur in individuals with BWS. The degree of organomegaly and associated complications can vary. In some cases, organomegaly may resolve or remain stable over time, while in others, it may lead to functional impairment and require ongoing management.
Macrosomia and Growth: Infants with BWS often present with macrosomia (excessive body size) and overgrowth. While overgrowth tends to be most prominent during the first few years of life, it may persist into childhood. The prognosis for growth largely depends on the severity of macrosomia and whether it leads to associated complications such as obesity or orthopedic issues.
Neurodevelopmental Challenges: Some individuals with BWS may experience neurodevelopmental challenges, including speech and language delays, cognitive impairments, or behavioral issues. The prognosis for neurodevelopmental outcomes can vary, and early intervention with appropriate therapies and support can help optimize developmental potential.
Surgical Interventions: The need for surgical interventions, such as repair of abdominal wall defects or orthopedic procedures, can influence the prognosis. The outcomes of surgical procedures depend on the specific indications, timing, and the expertise of the surgical team.
Clinical history
The clinical history of Beckwith-Wiedemann Syndrome (BWS) can vary among affected individuals, as the syndrome is characterized by a range of features. Here are some key aspects of the clinical history associated with BWS:
Prenatal History: In some cases, BWS may be suspected prenatally due to findings on ultrasound or other prenatal imaging. Features such as macrosomia (excessive fetal growth), polyhydramnios (excess amniotic fluid), and abdominal wall defects, such as omphalocele or umbilical hernia, may be detected during prenatal evaluation.
Macrosomia: Macrosomia refers to excessive fetal or postnatal growth. Infants with BWS often have a larger birth weight and length compared to their peers. The degree of macrosomia can vary, ranging from mild to severe. Overgrowth is most prominent during the first few years of life, but it may persist into childhood.
Macroglossia: Macroglossia, or enlargement of the tongue, is a common feature of BWS. It can be present at birth or become more apparent during infancy. Macroglossia can cause feeding difficulties, speech delays, and dental issues.
Abdominal Wall Defects: Approximately 70-80% of individuals with BWS have abdominal wall defects. These defects can include umbilical hernia (a protrusion of abdominal contents through the belly button), omphalocele (abdominal organs protruding outside the body through the umbilical cord), or diastasis recti (separation of the abdominal muscles).
Organomegaly: Enlargement of organs, such as the liver, kidneys, or adrenal glands, may occur in individuals with BWS. The degree of organomegaly can vary, and it may be detected during physical examination or through imaging studies.
Neonatal Hypoglycemia: Neonatal hypoglycemia, or low blood sugar levels shortly after birth, can occur in infants with BWS. It is usually transient but may require monitoring and management to maintain stable blood sugar levels.
Hemihypertrophy: Hemihypertrophy refers to asymmetric overgrowth of one side of the body. It may manifest as one limb or one side of the body being larger than the other. Hemihypertrophy can be present in some individuals with BWS.
Increased Tumor Risk: Individuals with BWS have an increased risk of developing certain tumors, particularly Wilms tumor (a type of kidney cancer) and hepatoblastoma (a type of liver cancer). Regular tumor screening and surveillance are recommended in affected individuals.
Physical examination
The physical examination of an individual with Beckwith-Wiedemann Syndrome (BWS) aims to identify the characteristic clinical features associated with the syndrome. Here are the key aspects that may be assessed during the physical examination:
General Appearance: The overall appearance of individuals with BWS can vary, but they may exhibit features of macrosomia (excessive body size) and overgrowth. The assessment includes observing the height, weight, and overall body proportions.
Facial Features: While BWS does not have specific facial characteristics, some individuals may have subtle facial differences. These can include a large or prominent forehead, wide-set eyes, and a round face. However, it’s important to note that the facial appearance in BWS can be variable and not present in all cases.
Macroglossia: Macroglossia, or an enlarged tongue, is a common finding in BWS. During the examination, the size and appearance of the tongue are assessed. Macroglossia can cause the tongue to protrude beyond the oral cavity and may contribute to feeding difficulties or speech delays.
Abdominal Wall Defects: Abdominal examination is performed to assess for any abdominal wall defects that are commonly associated with BWS. These may include umbilical hernia (protrusion of abdominal contents through the belly button), omphalocele (protrusion of abdominal organs outside the body through the umbilical cord), or diastasis recti (separation of the abdominal muscles).
Organomegaly: The size and consistency of abdominal organs, such as the liver, kidneys, and adrenal glands, may be assessed during the examination. Enlargement or abnormalities in the size or shape of these organs can indicate organomegaly, which is commonly seen in individuals with BWS.
Limb and Body Asymmetry: Asymmetrical overgrowth, known as hemihypertrophy, can be present in individuals with BWS. During the examination, the limbs and body are observed for any differences in size or length between the left and right sides.
Skin Abnormalities: Certain skin findings, such as birthmarks or nevi (pigmented skin lesions), may be observed in individuals with BWS. These skin abnormalities are not specific to BWS but can be present in some cases.
Differential diagnosis
When evaluating a patient with suspected Beckwith-Wiedemann Syndrome (BWS), it is important to consider other conditions that may present with similar features. The differential diagnosis of BWS includes:
Simpson-Golabi-Behmel Syndrome (SGBS): SGBS is a genetic disorder that shares some clinical features with BWS, such as macrosomia (large body size), macroglossia (enlarged tongue), and organomegaly. However, SGBS is associated with distinctive facial features, skeletal abnormalities, and an increased risk of certain tumors. Genetic testing can help differentiate between BWS and SGBS.
Silver-Russell Syndrome (SRS): SRS is a genetic disorder characterized by growth restriction, asymmetric body size, and distinctive facial features. Although there can be some overlapping features with BWS, the absence of macrosomia and the presence of growth restriction and asymmetry are more typical of SRS.
Perlman Syndrome: Perlman syndrome is a rare genetic disorder characterized by macrosomia, visceromegaly (enlarged abdominal organs), polyhydramnios (excessive amniotic fluid), and distinctive facial features. Renal abnormalities and an increased risk of Wilms tumor are also seen in Perlman syndrome. Genetic testing can differentiate between Perlman syndrome and BWS.
Overgrowth Syndromes: There are other genetic overgrowth syndromes that can present with macrosomia and features similar to BWS, such as Sotos syndrome, Weaver syndrome, and Marshall-Smith syndrome. Each of these syndromes has specific clinical features that can help distinguish them from BWS.
Isolated Hemihypertrophy: Hemihypertrophy, or asymmetric overgrowth of one side of the body, can be seen in BWS. However, isolated hemihypertrophy without other features of BWS is a separate condition and should be considered in the differential diagnosis.
Other Genetic Syndromes: There are several other genetic syndromes that may have overlapping features with BWS, such as Prader-Willi syndrome, Angelman syndrome, and Russell-Silver syndrome. Genetic testing and a careful evaluation of clinical features are necessary to differentiate these syndromes from BWS.
The treatment of Beckwith-Wiedemann Syndrome (BWS) is primarily focused on managing the specific symptoms and associated complications that may arise. The approach to treatment involves a multidisciplinary team of healthcare professionals who work together to provide comprehensive care. Here are some key aspects of the treatment for BWS:
Management of Hypoglycemia: Neonatal hypoglycemia, or low blood sugar levels shortly after birth, is a common concern in infants with BWS. It may require careful monitoring and management to maintain stable blood sugar levels. This can involve frequent feedings, glucose monitoring, and in some cases, intravenous glucose administration.
Feeding Support: Macroglossia (enlarged tongue) and other oral motor difficulties associated with BWS can lead to feeding challenges. Support from a pediatric feeding specialist, such as a speech-language pathologist or occupational therapist, may be beneficial in optimizing feeding techniques and ensuring adequate nutrition.
Surgical Intervention: Abdominal wall defects, such as umbilical hernia or omphalocele, may require surgical repair. The timing and necessity of surgery depend on the severity and clinical presentation of the specific defect.
Tumor Surveillance: Individuals with BWS have an increased risk of developing certain tumors, most notably Wilms tumor (kidney cancer) and hepatoblastoma (liver cancer). Regular tumor screening and surveillance protocols, including imaging studies and laboratory tests, are recommended to detect and manage tumors at an early stage.
Orthopedic Management: Hemihypertrophy, or asymmetric overgrowth of one side of the body, may require orthopedic assessment and management. This can involve monitoring the musculoskeletal system, addressing limb length discrepancies, and managing any associated orthopedic conditions.
Dental Care: Macroglossia and other oral features in BWS can contribute to dental problems, such as malocclusion and overcrowding of teeth. Regular dental examinations and appropriate dental interventions, including orthodontic treatment, may be necessary to maintain oral health.
Psychosocial Support: BWS can have a significant impact on individuals and families, both physically and emotionally. Psychosocial support, including counseling, support groups, and access to resources, can help address the emotional and psychological aspects of living with BWS.
https://www.ncbi.nlm.nih.gov/books/NBK558993/
medtigo
Beckwith-Wiedemann Syndrome
Updated :
June 11, 2024
Beckwith-Wiedemann Syndrome (BWS) is a rare genetic disorder characterized by various features that affect growth and development. It was named after the two physicians who independently described the syndrome in the 1960s: Dr. John Bruce Beckwith and Dr. Hans-Rudolf Wiedemann.
BWS is typically present at birth and is associated with abnormalities in the regulation of genes involved in growth and development. It is caused by genetic and epigenetic alterations that affect the expression of certain genes on chromosome 11.
Beckwith-Wiedemann Syndrome (BWS) is considered a rare disorder, but its exact prevalence is difficult to determine due to its variable clinical presentation and underdiagnosis. The reported prevalence of BWS ranges from approximately 1 in 10,000 to 1 in 15,000 live births. BWS affects both males and females and has been reported in various ethnic groups and geographical regions worldwide.
There is no specific geographic or ethnic predisposition for the syndrome. Certain factors have been associated with an increased risk of BWS, including advanced maternal age (mothers older than 35 years), multiple pregnancies (twins, triplets, etc.), and assisted reproductive technologies (such as in vitro fertilization). These factors may be associated with an increased frequency of epigenetic changes that contribute to the development of BWS.
Beckwith-Wiedemann Syndrome (BWS) is a complex genetic disorder characterized by alterations in the regulation of gene expression on chromosome 11. The pathophysiology of BWS involves genetic and epigenetic changes that disrupt the normal growth and development of various tissues and organs.
The majority of BWS cases (approximately 85%) are sporadic, meaning they occur randomly and are not inherited from parents. These cases are usually associated with abnormalities in a region on chromosome 11 called 11p15.5. This region contains several imprinted genes that play a role in growth regulation and development.
Imprinting refers to the process by which certain genes are “marked” or “stamped” with instructions from either the mother or father. In BWS, there is disruption in the normal imprinting patterns of genes in the 11p15.5 region. This disruption can occur through different mechanisms, including:
Loss of Imprinting: In some cases of BWS, there is a loss of imprinting (LOI) at specific genes, such as insulin-like growth factor 2 (IGF2) and H19. LOI leads to the biallelic expression (expression from both the maternal and paternal alleles) of these genes, which can result in increased cell growth and proliferation.
Abnormal DNA Methylation: DNA methylation is an epigenetic modification that can influence gene expression. In BWS, there can be abnormal DNA methylation patterns in the 11p15.5 region, affecting genes such as IGF2, H19, and KCNQ1OT1. These abnormalities in DNA methylation can disrupt the normal regulation of gene expression and contribute to the characteristic features of BWS.
Chromosomal Abnormalities: In a small percentage of BWS cases, there may be chromosomal abnormalities involving chromosome 11, such as duplications or translocations. These structural alterations can disrupt the normal functioning of genes in the 11p15.5 region, leading to BWS symptoms.
The altered gene expression patterns in BWS can affect various tissues and organs, resulting in the characteristic clinical features of the syndrome. These features can include overgrowth, macroglossia (enlarged tongue), abdominal wall defects, organomegaly (enlarged organs), neonatal hypoglycemia (low blood sugar), and an increased risk of certain tumors, such as Wilms tumor and hepatoblastoma. The specific mechanisms by which the genetic and epigenetic alterations lead to the clinical manifestations of BWS are still not fully understood.
Further research is needed to elucidate the precise pathophysiological mechanisms and the interplay between the disrupted genes and signaling pathways involved in BWS. Understanding the underlying pathophysiology of BWS is important for improved diagnosis, genetic counseling, and the development of targeted therapies or interventions to manage the symptoms and complications associated with the syndrome.
The etiology of Beckwith-Wiedemann Syndrome (BWS) involves genetic and epigenetic factors that lead to alterations in the regulation of gene expression on chromosome 11. The majority of BWS cases (approximately 85%) are sporadic, meaning they occur randomly and are not inherited from parents. However, around 10-15% of cases are inherited in an autosomal dominant manner, meaning they can be passed from an affected parent to their children.
Here are the key factors contributing to the etiology of BWS:
Genetic Abnormalities: The most common genetic abnormality associated with BWS involves alterations in a region on chromosome 11 called 11p15.5. This region contains several imprinted genes that play a role in growth regulation and development. Imprinting refers to the process by which certain genes are marked or stamped with instructions from either the mother or father. In BWS, there can be disruptions in the normal imprinting patterns of genes in the 11p15.5 region. This disruption can occur through different mechanisms, including loss of imprinting (LOI) and abnormal DNA methylation.
Loss of Imprinting (LOI): Loss of imprinting occurs when there is a disruption in the normal silencing or activation of specific genes from one parent. In BWS, LOI can lead to biallelic (both maternal and paternal) expression of certain genes, such as insulin-like growth factor 2 (IGF2), which can result in increased cell growth and proliferation.
Abnormal DNA Methylation: DNA methylation is an epigenetic modification that can influence gene expression. In BWS, there can be abnormal DNA methylation patterns in the 11p15.5 region, affecting genes such as IGF2, H19, and KCNQ1OT1. These abnormalities in DNA methylation can disrupt the normal regulation of gene expression and contribute to the characteristic features of BWS.
Chromosomal Abnormalities: In a small percentage of BWS cases, there may be chromosomal abnormalities involving chromosome 11, such as duplications or translocations. These structural alterations can disrupt the normal functioning of genes in the 11p15.5 region, leading to BWS symptoms.
The prognosis of Beckwith-Wiedemann Syndrome (BWS) can vary widely depending on the specific features and complications present in each individual. While some individuals with BWS have a relatively mild course and lead healthy lives, others may experience more severe manifestations and face greater challenges. Here are some factors that can influence the prognosis of BWS:
Tumor Risk: The most significant factor impacting the prognosis of BWS is the increased risk of developing tumors, particularly Wilms tumor (kidney cancer) and hepatoblastoma (liver cancer). The prognosis for tumor development depends on various factors, including the size, stage, and response to treatment. Early detection through regular tumor surveillance and prompt intervention can improve outcomes and prognosis.
Organomegaly: Enlargement of organs, such as the liver, kidneys, or adrenal glands, may occur in individuals with BWS. The degree of organomegaly and associated complications can vary. In some cases, organomegaly may resolve or remain stable over time, while in others, it may lead to functional impairment and require ongoing management.
Macrosomia and Growth: Infants with BWS often present with macrosomia (excessive body size) and overgrowth. While overgrowth tends to be most prominent during the first few years of life, it may persist into childhood. The prognosis for growth largely depends on the severity of macrosomia and whether it leads to associated complications such as obesity or orthopedic issues.
Neurodevelopmental Challenges: Some individuals with BWS may experience neurodevelopmental challenges, including speech and language delays, cognitive impairments, or behavioral issues. The prognosis for neurodevelopmental outcomes can vary, and early intervention with appropriate therapies and support can help optimize developmental potential.
Surgical Interventions: The need for surgical interventions, such as repair of abdominal wall defects or orthopedic procedures, can influence the prognosis. The outcomes of surgical procedures depend on the specific indications, timing, and the expertise of the surgical team.
Clinical history
The clinical history of Beckwith-Wiedemann Syndrome (BWS) can vary among affected individuals, as the syndrome is characterized by a range of features. Here are some key aspects of the clinical history associated with BWS:
Prenatal History: In some cases, BWS may be suspected prenatally due to findings on ultrasound or other prenatal imaging. Features such as macrosomia (excessive fetal growth), polyhydramnios (excess amniotic fluid), and abdominal wall defects, such as omphalocele or umbilical hernia, may be detected during prenatal evaluation.
Macrosomia: Macrosomia refers to excessive fetal or postnatal growth. Infants with BWS often have a larger birth weight and length compared to their peers. The degree of macrosomia can vary, ranging from mild to severe. Overgrowth is most prominent during the first few years of life, but it may persist into childhood.
Macroglossia: Macroglossia, or enlargement of the tongue, is a common feature of BWS. It can be present at birth or become more apparent during infancy. Macroglossia can cause feeding difficulties, speech delays, and dental issues.
Abdominal Wall Defects: Approximately 70-80% of individuals with BWS have abdominal wall defects. These defects can include umbilical hernia (a protrusion of abdominal contents through the belly button), omphalocele (abdominal organs protruding outside the body through the umbilical cord), or diastasis recti (separation of the abdominal muscles).
Organomegaly: Enlargement of organs, such as the liver, kidneys, or adrenal glands, may occur in individuals with BWS. The degree of organomegaly can vary, and it may be detected during physical examination or through imaging studies.
Neonatal Hypoglycemia: Neonatal hypoglycemia, or low blood sugar levels shortly after birth, can occur in infants with BWS. It is usually transient but may require monitoring and management to maintain stable blood sugar levels.
Hemihypertrophy: Hemihypertrophy refers to asymmetric overgrowth of one side of the body. It may manifest as one limb or one side of the body being larger than the other. Hemihypertrophy can be present in some individuals with BWS.
Increased Tumor Risk: Individuals with BWS have an increased risk of developing certain tumors, particularly Wilms tumor (a type of kidney cancer) and hepatoblastoma (a type of liver cancer). Regular tumor screening and surveillance are recommended in affected individuals.
Physical examination
The physical examination of an individual with Beckwith-Wiedemann Syndrome (BWS) aims to identify the characteristic clinical features associated with the syndrome. Here are the key aspects that may be assessed during the physical examination:
General Appearance: The overall appearance of individuals with BWS can vary, but they may exhibit features of macrosomia (excessive body size) and overgrowth. The assessment includes observing the height, weight, and overall body proportions.
Facial Features: While BWS does not have specific facial characteristics, some individuals may have subtle facial differences. These can include a large or prominent forehead, wide-set eyes, and a round face. However, it’s important to note that the facial appearance in BWS can be variable and not present in all cases.
Macroglossia: Macroglossia, or an enlarged tongue, is a common finding in BWS. During the examination, the size and appearance of the tongue are assessed. Macroglossia can cause the tongue to protrude beyond the oral cavity and may contribute to feeding difficulties or speech delays.
Abdominal Wall Defects: Abdominal examination is performed to assess for any abdominal wall defects that are commonly associated with BWS. These may include umbilical hernia (protrusion of abdominal contents through the belly button), omphalocele (protrusion of abdominal organs outside the body through the umbilical cord), or diastasis recti (separation of the abdominal muscles).
Organomegaly: The size and consistency of abdominal organs, such as the liver, kidneys, and adrenal glands, may be assessed during the examination. Enlargement or abnormalities in the size or shape of these organs can indicate organomegaly, which is commonly seen in individuals with BWS.
Limb and Body Asymmetry: Asymmetrical overgrowth, known as hemihypertrophy, can be present in individuals with BWS. During the examination, the limbs and body are observed for any differences in size or length between the left and right sides.
Skin Abnormalities: Certain skin findings, such as birthmarks or nevi (pigmented skin lesions), may be observed in individuals with BWS. These skin abnormalities are not specific to BWS but can be present in some cases.
Differential diagnosis
When evaluating a patient with suspected Beckwith-Wiedemann Syndrome (BWS), it is important to consider other conditions that may present with similar features. The differential diagnosis of BWS includes:
Simpson-Golabi-Behmel Syndrome (SGBS): SGBS is a genetic disorder that shares some clinical features with BWS, such as macrosomia (large body size), macroglossia (enlarged tongue), and organomegaly. However, SGBS is associated with distinctive facial features, skeletal abnormalities, and an increased risk of certain tumors. Genetic testing can help differentiate between BWS and SGBS.
Silver-Russell Syndrome (SRS): SRS is a genetic disorder characterized by growth restriction, asymmetric body size, and distinctive facial features. Although there can be some overlapping features with BWS, the absence of macrosomia and the presence of growth restriction and asymmetry are more typical of SRS.
Perlman Syndrome: Perlman syndrome is a rare genetic disorder characterized by macrosomia, visceromegaly (enlarged abdominal organs), polyhydramnios (excessive amniotic fluid), and distinctive facial features. Renal abnormalities and an increased risk of Wilms tumor are also seen in Perlman syndrome. Genetic testing can differentiate between Perlman syndrome and BWS.
Overgrowth Syndromes: There are other genetic overgrowth syndromes that can present with macrosomia and features similar to BWS, such as Sotos syndrome, Weaver syndrome, and Marshall-Smith syndrome. Each of these syndromes has specific clinical features that can help distinguish them from BWS.
Isolated Hemihypertrophy: Hemihypertrophy, or asymmetric overgrowth of one side of the body, can be seen in BWS. However, isolated hemihypertrophy without other features of BWS is a separate condition and should be considered in the differential diagnosis.
Other Genetic Syndromes: There are several other genetic syndromes that may have overlapping features with BWS, such as Prader-Willi syndrome, Angelman syndrome, and Russell-Silver syndrome. Genetic testing and a careful evaluation of clinical features are necessary to differentiate these syndromes from BWS.
The treatment of Beckwith-Wiedemann Syndrome (BWS) is primarily focused on managing the specific symptoms and associated complications that may arise. The approach to treatment involves a multidisciplinary team of healthcare professionals who work together to provide comprehensive care. Here are some key aspects of the treatment for BWS:
Management of Hypoglycemia: Neonatal hypoglycemia, or low blood sugar levels shortly after birth, is a common concern in infants with BWS. It may require careful monitoring and management to maintain stable blood sugar levels. This can involve frequent feedings, glucose monitoring, and in some cases, intravenous glucose administration.
Feeding Support: Macroglossia (enlarged tongue) and other oral motor difficulties associated with BWS can lead to feeding challenges. Support from a pediatric feeding specialist, such as a speech-language pathologist or occupational therapist, may be beneficial in optimizing feeding techniques and ensuring adequate nutrition.
Surgical Intervention: Abdominal wall defects, such as umbilical hernia or omphalocele, may require surgical repair. The timing and necessity of surgery depend on the severity and clinical presentation of the specific defect.
Tumor Surveillance: Individuals with BWS have an increased risk of developing certain tumors, most notably Wilms tumor (kidney cancer) and hepatoblastoma (liver cancer). Regular tumor screening and surveillance protocols, including imaging studies and laboratory tests, are recommended to detect and manage tumors at an early stage.
Orthopedic Management: Hemihypertrophy, or asymmetric overgrowth of one side of the body, may require orthopedic assessment and management. This can involve monitoring the musculoskeletal system, addressing limb length discrepancies, and managing any associated orthopedic conditions.
Dental Care: Macroglossia and other oral features in BWS can contribute to dental problems, such as malocclusion and overcrowding of teeth. Regular dental examinations and appropriate dental interventions, including orthodontic treatment, may be necessary to maintain oral health.
Psychosocial Support: BWS can have a significant impact on individuals and families, both physically and emotionally. Psychosocial support, including counseling, support groups, and access to resources, can help address the emotional and psychological aspects of living with BWS.
https://www.ncbi.nlm.nih.gov/books/NBK558993/
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