Pancreatic agenesis is a rare type of
congenital
genetic disorder, which arises from innate
pancreas
malformation and the absence of pancreatic
tissues.
[3] Pancreatic agenesis is classified into four types, and the signs and symptoms vary among the affected individuals.
[3]
[4] The exact cause of pancreatic agenesis is not well studied due to the limited cases reported worldwide.
[5] Nevertheless, the most recognized mechanisms for pancreatic agenesis are
genetic mutations in the
PDX1 gene and
PTF1A gene, which lead to incomplete pancreatic development in the
fetus, subsequently inducing
agenesis.
[3] There is no standard method to diagnose pancreatic agenesis, but
medical imaging has been widely used in many medical case reports due to its ability to detect structural abnormalities in patients' pancreas.
[4] If symptoms appear, treatments are provided to alleviate the pain and prevent the worsening of tissues and
organ dysfunction.Cite error: A <ref>
tag is missing the closing </ref>
(see the
help page). Reports suggest that the most common type of pancreatic agenesis is partial
dorsal pancreatic agenesis, while the less common types are partial
ventral pancreatic agenesis and complete pancreatic agenesis, due to the incompatibility for humans to live.
[4]
[6]
[7]
Individuals with dorsal pancreatic agenesis will experience either a partial or complete failure in pancreatic development, referred to as partial dorsal pancreatic agenesis and complete dorsal pancreatic agenesis, respectively. [3] [4] The same theory applies to ventral pancreatic agenesis. [9]
Table 1. Types of pancreatic agenesis based on the degree and location of pancreatic malformation. [3] [5] [4] [7] [10]
Degree of pancreatic malformation | Location of pancreatic malformation | Types of pancreatic agenesis |
---|---|---|
Complete | Dorsal
Ventral |
Complete dorsal pancreatic agenesis
Complete ventral pancreatic agenesis |
Partial | Dorsal
Ventral |
Partial dorsal pancreatic agenesis
Partial ventral pancreatic agenesis |
Signs and symptoms of pancreatic agenesis vary among individuals due to different levels of disease severity. [3] The disease severity is determined by the degree of congenital malformation and the damaged pancreatic tissues. [3] [11] A greater pancreatic malformation indicates a more severe impairment of the pancreatic tissues, and thus, causing a deterioration in the normal digestive functions which further induces digestive diseases. [12]
Common symptoms associated with pancreatic agenesis are pancreatitis, diabetes mellitus, hyperglycemia, bile duct obstruction, abdominal pain. [12] [13] Recent research has suggested that 50% of the affected individuals developed hyperglycemia or the aforementioned symptoms, while the remaining half did not develop any symptom throughout their lifetime. [12] [14] [7] Other rare diseases associated with pancreatic agenesis are polysplenia and heterotaxy syndrome. [6] [15]
Medical complications refer to the accompanying symptoms found in affected individuals, which leads to further worsening of health conditions. [16] The common complications of pancreatic agenesis are pancreatitis, diabetes, tumors, and organ malformations. [17] Upon the published studies, most of these complications are not confirmed to have a causal relationship with pancreatic agenesis. [17]
Pancreatic agenesis is the failure of pancreatic development due to the absence of primordial germ cells in the embryonic stage. [26] [27] Nonetheless, the exact causes of pancreatic agenesis are not fully known. [6] [28] Many research studies proposed that the pathophysiological mechanisms are associated with genetic mutations and genetic inheritance. [3] [14] In research laboratories, the more well-known genetic mutations related to pancreatic agenesis are the PDX1 gene and PTF1A gene, while the less studied genetic mutations are the GATA4 gene, GATA6 gene, and Mnx1 gene. [5] [6] [11] [15] [17]
A mutation in the Pancreatic Duodenal Homeobox-1 (PDX1) gene is associated with pancreatic agenesis. [3] [29] [30] The PDX1 gene codes for the proliferation of the pancreas in the embryonic stage. [31] The PDX1 gene develops signals during the first three to eight weeks of embryogenesis (embryonic development), which is received by the pancreatic bud. [11] [32] [33] Upon release of signals, the pancreatic bud will differentiate into a complete pancreas composed of a neck, body, and tail. [32] [34] However, a mutation in the PDX1 gene will cause abnormal development of the pancreatic bud into an incomplete pancreas, and thus, leading to structural abnormalities and pancreatic dysfunctions. [29] [35]
Additionally, the PDX1 gene is suspected to be associated with various metabolic diseases in pancreatic agenesis patients. [34] [36] One commonly associated metabolic disease is diabetes mellitus. [3] [29] The PDX1 gene is a major transcription factor for the insulin gene, which controls the absorbing ability of pancreatic beta-cells and serves to maintain the body's blood glucose level. [11] [35] [37] A mutation of the PDX1 gene depletes the functional pancreatic beta-cells that sustain the body's blood glucose level in the normal range. [14] [29] Thus, the mutation induces hyperglycemia (high blood sugar level) and diabetes mellitus. [14] [29]
A missense mutation in the Pancreas Associated Transcription Factor 1a (PTF1A) gene is associated with the incidence of pancreatic agenesis. [3] A missense mutation is a specific type of genetic mutation in which a single based nucleotide in the DNA is changed, and results in a substitution of an amino acid that codes for a different protein. [38]
The PTF1A gene promotes the development of embryonic foregut endoderm to form a proper pancreas. [40] At an early stage, the PTF1A genes are expressed in progenitors of pancreatic ducts, endocrine, and exocrine cells of the pancreas. [41] At a later stage, the PTF1A gene controls the expression of the PDX1 gene for pancreatic development in the embryo[9]. When the PTF1A gene mutates, the embryonic foregut endoderm will fail to develop into a complete pancreas, and therefore, inducing pancreatic agenesis. [42] [43]
Furthermore, a missense mutation in the PTF1A gene is responsible for the inheritance of neonatal diabetes mellitus, which is associated with pancreatic agenesis. [3] [43] [44] Neonatal diabetes mellitus is an autosomal recessive syndrome, and it is a type of diabetes onset in the first six months in infancy. [44] If neonatal diabetes mellitus remains untreated, symptoms such as dehydration, muscle weakness, learning disabilities, and other health complications may develop. [45] Nonetheless, the occurrence of both neonatal diabetes mellitus and pancreatic agenesis is uncommon. [46]
Pancreatic agenesis is inherited by autosomal recessive or X-linked dominant mode at the neonatal or infancy stage. [3] [6] Research suggested that individuals who carry these affected genes may temporarily exhibit no symptoms or a historical record of pancreatic agenesis. [3] [6]
The diagnosis of pancreatic agenesis is not well-established due to the limited cases reported worldwide. Although there is no standard method to diagnose this disease, many clinicians use imaging examinations as the primary diagnostic tool for detecting pancreatic structural abnormalities. [47] [48] The choice of imaging techniques is based on the specific symptoms and clinical availability. [47] [48] In some cases, clinicians apply multiple imaging techniques to confirm the diagnosis of pancreatic agenesis. [13] [47] [48]
Imaging examination is commonly used by physicians to detect abdomen symptoms. [49] Recent research recommends to confirm pancreatic agenesis diagnosis by integrating one or more imaging examinations. [50] Despite limited clinical reports, endoscopic retrograde cholangiopancreatography (ERCP) is found to give the highest diagnostic values for pancreatic agenesis. [50]
Differential diagnostic tools are applied to differentiate pancreatic agenesis from diseases with overlapping symptoms. These diseases include pancreatic fat infiltration, chronic pancreatitis, atrophy in pancreatic body and tail. [17] For example, pancreatic fat infiltration bears a higher fat signal fraction (FSF) in MRI images and unique echo characteristics in ultrasound examination. [59] Chronic pancreatitis, the common mimicker to pancreatic agenesis, is featured by pancreas dividum and autodigestion despite it possesses similar structural abnormality under imaging examinations. [60] Recently, published research shows that chronic pancreatitis owns dilated pancreatic ducts compared with pancreatic agenesis. [61]
There is no universal agreement regarding the standard treatment of pancreatic agenesis. Most of the management measures and treatments focus on relieving symptoms and preventing further damage to pancreatic tissues. [17] Recent studies suggest simple pancreatic agenesis requires no special treatment, but severe complications need medical treatments, such as the top two common complications: hyperglycemia (up to 50%) and pancreatitis. [62] [63]
Pancreas agenesis is a rare congenital anomaly inherited by autosomal recessive alleles or X-linked dominant mode. [3] [9] Up to now, only around 50-100 cases of partial pancreas agenesis are reported, and the disease prevalence is estimated to be 1 in 1,000,000. [9]
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Warning: Default sort key "Pancreatic Agenesis" overrides earlier default sort key "Pancreatic agenesis".
Pancreatic agenesis is a rare type of
congenital
genetic disorder, which arises from innate
pancreas
malformation and the absence of pancreatic
tissues.
[3] Pancreatic agenesis is classified into four types, and the signs and symptoms vary among the affected individuals.
[3]
[4] The exact cause of pancreatic agenesis is not well studied due to the limited cases reported worldwide.
[5] Nevertheless, the most recognized mechanisms for pancreatic agenesis are
genetic mutations in the
PDX1 gene and
PTF1A gene, which lead to incomplete pancreatic development in the
fetus, subsequently inducing
agenesis.
[3] There is no standard method to diagnose pancreatic agenesis, but
medical imaging has been widely used in many medical case reports due to its ability to detect structural abnormalities in patients' pancreas.
[4] If symptoms appear, treatments are provided to alleviate the pain and prevent the worsening of tissues and
organ dysfunction.Cite error: A <ref>
tag is missing the closing </ref>
(see the
help page). Reports suggest that the most common type of pancreatic agenesis is partial
dorsal pancreatic agenesis, while the less common types are partial
ventral pancreatic agenesis and complete pancreatic agenesis, due to the incompatibility for humans to live.
[4]
[6]
[7]
Individuals with dorsal pancreatic agenesis will experience either a partial or complete failure in pancreatic development, referred to as partial dorsal pancreatic agenesis and complete dorsal pancreatic agenesis, respectively. [3] [4] The same theory applies to ventral pancreatic agenesis. [9]
Table 1. Types of pancreatic agenesis based on the degree and location of pancreatic malformation. [3] [5] [4] [7] [10]
Degree of pancreatic malformation | Location of pancreatic malformation | Types of pancreatic agenesis |
---|---|---|
Complete | Dorsal
Ventral |
Complete dorsal pancreatic agenesis
Complete ventral pancreatic agenesis |
Partial | Dorsal
Ventral |
Partial dorsal pancreatic agenesis
Partial ventral pancreatic agenesis |
Signs and symptoms of pancreatic agenesis vary among individuals due to different levels of disease severity. [3] The disease severity is determined by the degree of congenital malformation and the damaged pancreatic tissues. [3] [11] A greater pancreatic malformation indicates a more severe impairment of the pancreatic tissues, and thus, causing a deterioration in the normal digestive functions which further induces digestive diseases. [12]
Common symptoms associated with pancreatic agenesis are pancreatitis, diabetes mellitus, hyperglycemia, bile duct obstruction, abdominal pain. [12] [13] Recent research has suggested that 50% of the affected individuals developed hyperglycemia or the aforementioned symptoms, while the remaining half did not develop any symptom throughout their lifetime. [12] [14] [7] Other rare diseases associated with pancreatic agenesis are polysplenia and heterotaxy syndrome. [6] [15]
Medical complications refer to the accompanying symptoms found in affected individuals, which leads to further worsening of health conditions. [16] The common complications of pancreatic agenesis are pancreatitis, diabetes, tumors, and organ malformations. [17] Upon the published studies, most of these complications are not confirmed to have a causal relationship with pancreatic agenesis. [17]
Pancreatic agenesis is the failure of pancreatic development due to the absence of primordial germ cells in the embryonic stage. [26] [27] Nonetheless, the exact causes of pancreatic agenesis are not fully known. [6] [28] Many research studies proposed that the pathophysiological mechanisms are associated with genetic mutations and genetic inheritance. [3] [14] In research laboratories, the more well-known genetic mutations related to pancreatic agenesis are the PDX1 gene and PTF1A gene, while the less studied genetic mutations are the GATA4 gene, GATA6 gene, and Mnx1 gene. [5] [6] [11] [15] [17]
A mutation in the Pancreatic Duodenal Homeobox-1 (PDX1) gene is associated with pancreatic agenesis. [3] [29] [30] The PDX1 gene codes for the proliferation of the pancreas in the embryonic stage. [31] The PDX1 gene develops signals during the first three to eight weeks of embryogenesis (embryonic development), which is received by the pancreatic bud. [11] [32] [33] Upon release of signals, the pancreatic bud will differentiate into a complete pancreas composed of a neck, body, and tail. [32] [34] However, a mutation in the PDX1 gene will cause abnormal development of the pancreatic bud into an incomplete pancreas, and thus, leading to structural abnormalities and pancreatic dysfunctions. [29] [35]
Additionally, the PDX1 gene is suspected to be associated with various metabolic diseases in pancreatic agenesis patients. [34] [36] One commonly associated metabolic disease is diabetes mellitus. [3] [29] The PDX1 gene is a major transcription factor for the insulin gene, which controls the absorbing ability of pancreatic beta-cells and serves to maintain the body's blood glucose level. [11] [35] [37] A mutation of the PDX1 gene depletes the functional pancreatic beta-cells that sustain the body's blood glucose level in the normal range. [14] [29] Thus, the mutation induces hyperglycemia (high blood sugar level) and diabetes mellitus. [14] [29]
A missense mutation in the Pancreas Associated Transcription Factor 1a (PTF1A) gene is associated with the incidence of pancreatic agenesis. [3] A missense mutation is a specific type of genetic mutation in which a single based nucleotide in the DNA is changed, and results in a substitution of an amino acid that codes for a different protein. [38]
The PTF1A gene promotes the development of embryonic foregut endoderm to form a proper pancreas. [40] At an early stage, the PTF1A genes are expressed in progenitors of pancreatic ducts, endocrine, and exocrine cells of the pancreas. [41] At a later stage, the PTF1A gene controls the expression of the PDX1 gene for pancreatic development in the embryo[9]. When the PTF1A gene mutates, the embryonic foregut endoderm will fail to develop into a complete pancreas, and therefore, inducing pancreatic agenesis. [42] [43]
Furthermore, a missense mutation in the PTF1A gene is responsible for the inheritance of neonatal diabetes mellitus, which is associated with pancreatic agenesis. [3] [43] [44] Neonatal diabetes mellitus is an autosomal recessive syndrome, and it is a type of diabetes onset in the first six months in infancy. [44] If neonatal diabetes mellitus remains untreated, symptoms such as dehydration, muscle weakness, learning disabilities, and other health complications may develop. [45] Nonetheless, the occurrence of both neonatal diabetes mellitus and pancreatic agenesis is uncommon. [46]
Pancreatic agenesis is inherited by autosomal recessive or X-linked dominant mode at the neonatal or infancy stage. [3] [6] Research suggested that individuals who carry these affected genes may temporarily exhibit no symptoms or a historical record of pancreatic agenesis. [3] [6]
The diagnosis of pancreatic agenesis is not well-established due to the limited cases reported worldwide. Although there is no standard method to diagnose this disease, many clinicians use imaging examinations as the primary diagnostic tool for detecting pancreatic structural abnormalities. [47] [48] The choice of imaging techniques is based on the specific symptoms and clinical availability. [47] [48] In some cases, clinicians apply multiple imaging techniques to confirm the diagnosis of pancreatic agenesis. [13] [47] [48]
Imaging examination is commonly used by physicians to detect abdomen symptoms. [49] Recent research recommends to confirm pancreatic agenesis diagnosis by integrating one or more imaging examinations. [50] Despite limited clinical reports, endoscopic retrograde cholangiopancreatography (ERCP) is found to give the highest diagnostic values for pancreatic agenesis. [50]
Differential diagnostic tools are applied to differentiate pancreatic agenesis from diseases with overlapping symptoms. These diseases include pancreatic fat infiltration, chronic pancreatitis, atrophy in pancreatic body and tail. [17] For example, pancreatic fat infiltration bears a higher fat signal fraction (FSF) in MRI images and unique echo characteristics in ultrasound examination. [59] Chronic pancreatitis, the common mimicker to pancreatic agenesis, is featured by pancreas dividum and autodigestion despite it possesses similar structural abnormality under imaging examinations. [60] Recently, published research shows that chronic pancreatitis owns dilated pancreatic ducts compared with pancreatic agenesis. [61]
There is no universal agreement regarding the standard treatment of pancreatic agenesis. Most of the management measures and treatments focus on relieving symptoms and preventing further damage to pancreatic tissues. [17] Recent studies suggest simple pancreatic agenesis requires no special treatment, but severe complications need medical treatments, such as the top two common complications: hyperglycemia (up to 50%) and pancreatitis. [62] [63]
Pancreas agenesis is a rare congenital anomaly inherited by autosomal recessive alleles or X-linked dominant mode. [3] [9] Up to now, only around 50-100 cases of partial pancreas agenesis are reported, and the disease prevalence is estimated to be 1 in 1,000,000. [9]
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was invoked but never defined (see the
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Warning: Default sort key "Pancreatic Agenesis" overrides earlier default sort key "Pancreatic agenesis".