Hirschsprung Disease
Proto-Oncogene Proteins c-ret
Enteric Nervous System
SOXE Transcription Factors
Glial Cell Line-Derived Neurotrophic Factor Receptors
Receptor, Endothelin B
Waardenburg Syndrome
Endothelin-3
Receptor Protein-Tyrosine Kinases
Microcephaly
Glial Cell Line-Derived Neurotrophic Factor
Neural Crest
Multiple Endocrine Neoplasia Type 2a
Receptors, Endothelin
Facies
Penetrance
Mutation
Carcinoma, Medullary
High Mobility Group Proteins
Abnormalities, Multiple
Intellectual Disability
Drosophila Proteins
Proto-Oncogene Proteins
Haplotypes
Germ-Line Mutation
Nerve Growth Factors
Pedigree
Polymorphism, Single-Stranded Conformational
The Sox10(Dom) mouse: modeling the genetic variation of Waardenburg-Shah (WS4) syndrome. (1/339)
Hirschsprung disease (HSCR) is a multigenic neurocristopathy clinically recognized by aganglionosis of the distal gastrointestinal tract. Patients presenting with aganglionosis in association with hypopigmentation are classified as Waardenburg syndrome type 4 (Waardenburg-Shah, WS4). Variability in the disease phenotype of WS4 patients with equivalent mutations suggests the influence of genetic modifier loci in this disorder. Sox10(Dom)/+ mice exhibit variability of aganglionosis and hypopigmentation influenced by genetic background similar to that observed in WS4 patients. We have constructed Sox10(Dom)/+ congenic lines to segregate loci that modify the neural crest defects in these mice. Consistent with previous studies, increased lethality of Sox10(Dom)/+ animals resulted from a C57BL/6J locus(i). However, we also observed an increase in hypopigmentation in conjunction with a C3HeB/FeJLe-a/a locus(i). Linkage analysis localized a hypopigmentation modifier of the Dom phenotype to mouse chromosome 10 in close proximity to a previously reported modifier of hypopigmentation for the endothelin receptor B mouse model of WS4. To evaluate further the role of SOX10 in development and disease, we have performed comparative genomic analyses. An essential role for this gene in neural crest development is supported by zoo blot hybridizations that reveal extensive conservation throughout vertebrate evolution and by similar Northern blot expression profiles between mouse and man. Comparative sequence analysis of the mouse and human SOX10 gene have defined the exon-intron boundaries of SOX10 and facilitated mutation analysis leading to the identification of two new SOX10 mutations in individuals with WS4. Structural analysis of the HMG DNA-binding domain was performed to evaluate the effect of human mutations in this region. (+info)Investigation of germline GFR alpha-1 mutations in Hirschsprung disease. (2/339)
Inactivating mutations of the RET proto-oncogene and of one of its soluble ligand molecules, glial cell line derived neurotrophic factor (GDNF), have been found in a subset of patients with Hirschsprung disease (HSCR). However, the majority of HSCR mutations remain unidentified. As normal RET function requires a multicomponent ligand complex for activation, other members of the RET ligand complex are primary candidates for these mutations. We investigated the presence of mutations in another member of the RET signalling complex, GDNF family receptor alpha-1 (GFR alpha-1), in a panel of 269 independent cases of HSCR. We identified 10 polymorphisms at the GFR alpha-1 locus. Surprisingly, however, we did not identify any sequence variants in our HSCR population that were not also present in a normal control population. Our data suggest that mutations of the GFR alpha-1 gene are not a common aetiological event in HSCR. (+info)A Hirschsprung disease locus at 22q11? (3/339)
We report a boy with truncus arteriosus, dysmorphic features, developmental delay, passing hypotonia, short segment Hirschsprung disease (HSCR), and paroxysmal hypoventilation. FISH analysis showed an interstitial deletion in chromosome band 22q11.2 coinciding with the deletions found in DiGeorge syndrome and velocardiofacial syndrome. Mutation scanning of RET, GDNF, EDNRB, and EDN3, genes associated with Hirschsprung disease, showed no aberrations. Since we know of two more patients with velocardiofacial syndrome and HSCR, we hypothesise that a gene responsible for proper development of the enteric nervous system may be included in the 22q11.2 region. (+info)Primary laparoscopic-assisted endorectal colon pull-through for Hirschsprung's disease: a new gold standard. (4/339)
OBJECTIVE: To describe the surgical technique and early clinical results after a one-stage laparoscopic-assisted endorectal colon pull-through for Hirschsprung's disease. SUMMARY BACKGROUND DATA: Recent trends in surgery for Hirschsprung's disease have been toward earlier repair and fewer surgical stages. A one-stage pull-through for Hirschsprung's disease avoids the additional anesthesia, surgery, and complications of a colostomy. A laparoscopic-assisted approach diminishes surgical trauma to the peritoneal cavity. METHODS: The technique uses four small abdominal ports. The transition zone is initially identified by seromuscular biopsies obtained laparoscopically. A colon pedicle preserving the marginal artery is fashioned endoscopically. The rectal mobilization is performed transanally using an endorectal sleeve technique. The anastomosis is performed transanally 1 cm above the dentate line. This report discusses the outcome of primary laparoscopic pull-through in 80 patients performed at six pediatric surgery centers over the past 5 years. RESULTS: The age at surgery ranged from 3 days to 96 months. The average length of the surgical procedure was 2.5 hours. Almost all of the patients passed stool and flatus within 24 hours of surgery. The average time for discharge after surgery was 3.7 days. All 80 patients are currently alive and well. Most of the children are too young to evaluate for fecal continence, but 18 of the older children have been reported to be continent. CONCLUSION: Laparoscopic-assisted colon pull-through appears to reduce perioperative complications and postoperative recovery time dramatically. The technique is quickly learned and has been performed in multiple centers with consistently good results. (+info)Rectal biopsy for diagnosis of intestinal neuronal dysplasia in children: a prospective multicentre study on interobserver variation and clinical outcome. (5/339)
BACKGROUND: Intestinal neuronal dysplasia (IND) of the colonic submucous plexus is considered to be a congenital malformation of the enteric nervous system causing symptoms resembling those of Hirschsprung's disease. In contrast with the established diagnosis of aganglionosis using enzyme histochemistry, controversy exists over the diagnostic criteria of IND on rectal biopsies previously defined by a consensus report and the causal relation between morphological findings and clinical symptoms. AIMS: The interobserver variability was prospectively investigated with respect to final diagnoses and several histological features in rectal biopsy specimens from children suspected of having colonic motility disturbances. METHODS: 377 biopsy specimens from 108 children aged 4 days to 15 years were independently coded without knowledge of clinical symptoms by three experienced pathologists for 20 histological features, and a final diagnosis was given for every case. Interobserver variation for the different items and the final diagnosis were analysed using Cohen's kappa statistic. Clinical data at biopsy and outcome after 12 months were related to morphological findings. RESULTS: The three pathologists agreed completely with respect to the diagnosis Hirschsprung's disease (kappa = 1), but in only 14% of the children without aganglionosis. In 15 (17%) of the 87 children without aganglionosis, at least one pathologist judged the case as normal, while another diagnosed IND. kappa values were close to the zero value expected by chance for the diagnoses normal and IND. Young age was related to the presence of several morphological features-for example, acetylcholine esterase staining and presence of giant ganglia. Children with chronic constipation diagnosed as having IND, given no other specific diagnosis by any of the pathologists, were significantly younger (median 8.8 months) and had a higher cure rate after one year (60%) than constipated patients considered by all observers to have no histological abnormalities (median 6.1 years, cure rate 23%). CONCLUSIONS: In contrast with Hirschsprung's disease, there is a high interobserver variation with regard to the different morphological features and final diagnosis of IND, based on the criteria and conditions of the previous consensus report. The high frequency of histological "abnormalities" in young infants suggests that some of the features may represent a normal variant of postnatal development rather than a pathological process. Investigations using more refined and morphometric methods in rectal specimens from infants and children without bowel disease are needed to define the normal range of morphological appearance at different ages. These preliminary data indicate that, with current knowledge, rectal biopsy for diagnostic purposes should only be performed in constipated children for diagnosis of Hirschsprung's disease. (+info)RET proto-oncogene in the development of human cancer. (6/339)
The RET proto-oncogene, located on chromosome subband 10q11.2, encodes a receptor tyrosine kinase expressed in tissues and tumors derived from neural crest. Germline (present in every cell of the body) mutations in RET cause multiple endocrine neoplasia type 2 (MEN 2), an inherited cancer syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PC), and hyperparathyroidism (HPT). This knowledge has allowed molecular diagnosis and presymptomatic DNA-based testing to become possible. RET testing is considered the standard of care in MEN 2 families because clinical decisions are made based on the results of such gene testing. There appears to be a correlation between specific RET mutation type and organ-specific tumor development. Such knowledge might be useful in tailoring targeted surveillance in the near future. Somatic (in the tumor only) RET mutations have been found in a proportion of sporadic MTCs and PCs. Whether the presence of somatic RET mutation is associated with a poor prognosis is currently being investigated as another tool for molecular medicine. (+info)Point nucleotidic changes in both the RET proto-oncogene and the endothelin-B receptor gene in a Hirschsprung disease patient associated with Down syndrome. (7/339)
A short-segment Hirschsprung disease (HSCR) patient associated with 21 trisomy showing point nucleotidic changes in both the receptor tyrosine kinase (RET) proto-oncogene and the endothelin-B receptor (EDNRB) gene is reported. A T to A heterozygous transition at the splicing donor site of the intron 10 in the RET proto-oncogene, and a G to A heterozygous substitution in non-coding region in the exon 1 of the EDNRB gene were observed. The familial analysis with these genes revealed that the origin of the former mutation was de novo and the latter one was maternal. No patient has been reported with two points mutations in different pathogenetically susceptible loci for HSCR. There is genetic evidence that the RET and EDNRB genes may interact in their susceptibility leading to HSCR. (+info)Clostridium difficile colitis associated with infant botulism: near-fatal case analogous to Hirschsprung's enterocolitis. (8/339)
We present the first five reported cases of Clostridium difficile-associated diarrhea (CDAD) in children with infant botulism caused by Clostridium botulinum. We compare two fulminant cases of colitis in children with colonic stasis, the first caused by infant botulism and the second caused by Hirschsprung's disease. In both children, colitis was accompanied by hypovolemia, hypotension, profuse ascites, pulmonary effusion, restrictive pulmonary disease, and femoral-caval thrombosis. Laboratory findings included pronounced leukocytosis, hypoalbuminemia, hyponatremia, coagulopathy, and, when examined in the child with infant botulism, detection of C. difficile toxin in ascites. CDAD recurred in both children, even though difficile cytotoxin was undetectable in stool after prolonged initial therapy. Four children who had both infant botulism and milder CDAD also are described. Colonic stasis, whether acquired, as in infant botulism, or congenital, as in Hirschsprung's disease, may contribute to the susceptibility to and the severity of CDAD. (+info)Hirschsprung disease is a gastrointestinal disorder that affects the large intestine, specifically the section known as the colon. This condition is congenital, meaning it is present at birth. It occurs due to the absence of ganglion cells (nerve cells) in the bowel's muscular wall, which are responsible for coordinating muscle contractions that move food through the digestive tract.
The affected segment of the colon cannot relax and propel the contents within it, leading to various symptoms such as constipation, intestinal obstruction, or even bowel perforation in severe cases. Common diagnostic methods include rectal suction biopsy, anorectal manometry, and contrast enema studies. Treatment typically involves surgical removal of the aganglionic segment and reattachment of the normal colon to the anus (known as a pull-through procedure).
Proto-oncogene proteins c-RET are a group of gene products that play crucial roles in the development and functioning of the nervous system, as well as in other tissues. The c-RET proto-oncogene encodes a receptor tyrosine kinase, which is a type of enzyme that helps transmit signals from the outside to the inside of cells. This receptor is activated by binding to its ligands, leading to the activation of various signaling pathways that regulate cell growth, differentiation, and survival.
Mutations in the c-RET proto-oncogene can lead to its overactivation, resulting in the conversion of this gene into an oncogene. Oncogenes are genes that have the potential to cause cancer when they are mutated or abnormally expressed. Activating mutations in c-RET have been implicated in several types of human cancers, including multiple endocrine neoplasia type 2 (MEN2), papillary thyroid carcinoma, and certain types of lung and kidney cancers. These mutations can lead to the constitutive activation of c-RET, resulting in uncontrolled cell growth and tumor formation.
The enteric nervous system (ENS) is a part of the autonomic nervous system that directly controls the gastrointestinal tract, including the stomach, small intestine, colon, and rectum. It is sometimes referred to as the "second brain" because it can operate independently of the central nervous system (CNS).
The ENS contains around 500 million neurons that are organized into two main plexuses: the myenteric plexus, which lies between the longitudinal and circular muscle layers of the gut, and the submucosal plexus, which is located in the submucosa. These plexuses contain various types of neurons that are responsible for regulating gastrointestinal motility, secretion, and blood flow.
The ENS can communicate with the CNS through afferent nerve fibers that transmit information about the state of the gut to the brain, and efferent nerve fibers that carry signals from the brain back to the ENS. However, the ENS is also capable of functioning independently of the CNS, allowing it to regulate gastrointestinal functions in response to local stimuli such as food intake, inflammation, or infection.
SOXE transcription factors are a subgroup of the SOX (SRY-related HMG box) family of proteins, which are involved in various developmental processes, including cell fate specification and differentiation. The SOXE group includes SOX8, SOX9, and SOX10, all of which contain a conserved high mobility group (HMG) box DNA-binding domain. They play crucial roles in the development of several tissues, such as the nervous system, skeletal system, and urogenital system.
SOXE transcription factors are known to regulate gene expression by binding to specific DNA sequences, often acting in combination with other transcription factors to control various cellular processes. Dysregulation of SOXE transcription factors has been implicated in several human diseases, including cancer and neurodevelopmental disorders.
Glial cell line-derived neurotrophic factor (GDNF) receptors are a group of proteins found on the surface of certain cells in the body that bind to GDNF and transmit signals into the cell, thereby activating various cellular responses. GDNF is a type of signaling protein called a neurotrophic factor, which supports the survival and development of neurons (nerve cells).
The GDNF receptor complex consists of two main components: the Ret tyrosine kinase receptor and a glycosylphosphatidylinositol (GPI)-anchored coreceptor called GDNF family receptor alpha (GFRα). There are four different GFRα isoforms (GFRα1, GFRα2, GFRα3, and GFRα4) that can form complexes with Ret and bind to different members of the GDNF ligand family.
When GDNF binds to the GFRα-Ret complex, it induces a conformational change leading to Ret autophosphorylation and activation of various downstream signaling pathways, including Ras/MAPK, PI3K/Akt, and PLCγ. These signaling cascades ultimately regulate cell survival, proliferation, differentiation, and migration, depending on the cellular context.
GDNF receptors are widely expressed in various tissues, but they have crucial roles in the nervous system, where they support neuronal survival, promote axon growth and guidance, and maintain synaptic plasticity. Dysregulation of GDNF signaling has been implicated in several neurological disorders, such as Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS).
The Endothelin B (ETB) receptor is a type of G protein-coupled receptor that binds to endothelin, a potent vasoconstrictor peptide. ETB receptors are expressed in various tissues, including vascular endothelial cells and smooth muscle cells. When endothelin binds to the ETB receptor, it can cause both vasodilation and vasoconstriction, depending on the location of the receptor. In endothelial cells, activation of ETB receptors leads to the production of nitric oxide, a potent vasodilator. However, in vascular smooth muscle cells, activation of ETB receptors can cause vasoconstriction by increasing intracellular calcium levels.
ETB receptors have also been implicated in various physiological and pathophysiological processes, including cardiovascular function, kidney function, and neurotransmission. In the cardiovascular system, ETB receptors play a role in regulating blood pressure and vascular remodeling. In the kidneys, they are involved in the regulation of sodium and water balance. Additionally, ETB receptors have been implicated in the development of pulmonary hypertension, heart failure, and chronic kidney disease.
Overall, Endothelin B receptors play a critical role in regulating various physiological processes, and their dysregulation has been associated with several pathological conditions.
Waardenburg Syndrome is a genetic disorder that affects the development of melanin, a pigment responsible for hair, skin, and eye color. Named after the Dutch ophthalmologist Petrus Waardenburg who first described it in 1907, this syndrome is characterized by distinctive physical features and hearing loss.
There are four types of Waardenburg Syldrome (WS1, WS2, WS3, and WS4), each with varying degrees of symptoms. Common features include:
1. Differential coloring of the hair, skin, and eyes (poliosis, vitiligo, and heterochromia)
2. Distinctive facial features (wide-set eyes, broad nasal root, and a high arched or cleft palate)
3. Hearing loss, which can be unilateral (one-sided) or bilateral (both-sided), conductive, sensorineural, or mixed
4. Pigmentary changes in the iris, such as different colors between the eyes or within one eye
5. Sometimes, musculoskeletal abnormalities and/or developmental delays
WS1 and WS2 are more common than WS3 and WS4. The genetic causes of Waardenburg Syndrome involve mutations in several different genes associated with melanin production and transport. These include PAX3, MITF, SNAI2, EDN3, and EDNRB.
Diagnosis is typically based on clinical findings, including physical features and hearing tests. Genetic testing can confirm the diagnosis and help determine the specific type of Waardenburg Syndrome. Treatment usually involves addressing individual symptoms, such as using hearing aids or cochlear implants for hearing loss and managing any skin or eye concerns.
Endothelin-3 (ET-3) is a member of the endothelin family, which are small peptides with potent vasoconstrictor properties. ET-3 is primarily produced by neurons in the central and peripheral nervous system, and it plays important roles in the development and regulation of various physiological functions, including cardiovascular function, neurotransmission, and cell proliferation.
ET-3 exerts its effects by binding to specific G protein-coupled receptors, known as endothelin A (ETA) and endothelin B (ETB) receptors. These receptors are widely distributed throughout the body, including in the cardiovascular, respiratory, gastrointestinal, and genitourinary systems.
In addition to its role as a potent vasoconstrictor, ET-3 has been implicated in various pathological conditions, such as hypertension, heart failure, pulmonary arterial hypertension, and cancer. In recent years, there has been growing interest in the potential therapeutic use of endothelin receptor antagonists to treat these conditions.
Receptor Protein-Tyrosine Kinases (RTKs) are a type of transmembrane receptors found on the cell surface that play a crucial role in signal transduction and regulation of various cellular processes, including cell growth, differentiation, metabolism, and survival. They are called "tyrosine kinases" because they possess an intrinsic enzymatic activity that catalyzes the transfer of a phosphate group from ATP to tyrosine residues on target proteins, thereby modulating their function.
RTKs are composed of three main domains: an extracellular domain that binds to specific ligands (growth factors, hormones, or cytokines), a transmembrane domain that spans the cell membrane, and an intracellular domain with tyrosine kinase activity. Upon ligand binding, RTKs undergo conformational changes that lead to their dimerization or oligomerization, which in turn activates their tyrosine kinase activity. Activated RTKs then phosphorylate specific tyrosine residues on downstream signaling proteins, initiating a cascade of intracellular signaling events that ultimately result in the appropriate cellular response.
Dysregulation of RTK signaling has been implicated in various human diseases, including cancer, diabetes, and developmental disorders. As such, RTKs are important targets for therapeutic intervention in these conditions.
Microcephaly is a medical condition where an individual has a smaller than average head size. The circumference of the head is significantly below the normal range for age and sex. This condition is typically caused by abnormal brain development, which can be due to genetic factors or environmental influences such as infections or exposure to harmful substances during pregnancy.
Microcephaly can be present at birth (congenital) or develop in the first few years of life. People with microcephaly often have intellectual disabilities, delayed development, and other neurological problems. However, the severity of these issues can vary widely, ranging from mild to severe. It is important to note that not all individuals with microcephaly will experience significant impairments or challenges.
Glial Cell Line-Derived Neurotrophic Factor (GDNF) is a protein that plays a crucial role in the survival, development, and function of certain neurons in the nervous system. It is a member of the transforming growth factor-β (TGF-β) superfamily and was initially identified for its ability to support the survival and differentiation of midbrain dopaminergic neurons, which are critical for movement control and motivation. GDNF also supports other types of neurons, including motor neurons and sensory neurons. It exerts its effects by binding to a receptor complex consisting of GFRα1 and RET tyrosine kinase receptors, activating intracellular signaling pathways that promote neuronal survival, growth, and synaptic plasticity. GDNF has been investigated as a potential therapeutic agent for various neurodegenerative disorders, including Parkinson's disease and amyotrophic lateral sclerosis (ALS).
The neural crest is a transient, multipotent embryonic cell population that originates from the ectoderm (outermost layer) of the developing neural tube (precursor to the central nervous system). These cells undergo an epithelial-to-mesenchymal transition and migrate throughout the embryo, giving rise to a diverse array of cell types and structures.
Neural crest cells differentiate into various tissues, including:
1. Peripheral nervous system (PNS) components: sensory neurons, sympathetic and parasympathetic ganglia, and glial cells (e.g., Schwann cells).
2. Facial bones and cartilage, as well as connective tissue of the skull.
3. Melanocytes, which are pigment-producing cells in the skin.
4. Smooth muscle cells in major blood vessels, heart, gastrointestinal tract, and other organs.
5. Secretory cells in endocrine glands (e.g., chromaffin cells of the adrenal medulla).
6. Parts of the eye, such as the cornea and iris stroma.
7. Dental tissues, including dentin, cementum, and dental pulp.
Due to their wide-ranging contributions to various tissues and organs, neural crest cells play a crucial role in embryonic development and organogenesis. Abnormalities in neural crest cell migration or differentiation can lead to several congenital disorders, such as neurocristopathies.
Multiple Endocrine Neoplasia Type 2a (MEN 2A) is a rare genetic disorder characterized by the development of tumors in various endocrine glands. It is caused by a mutation in the RET gene. The condition typically involves the following three endocrine glands:
1. Medullary Thyroid Carcinoma (MTC): Almost all patients with MEN 2A develop this type of thyroid cancer, which arises from the parafollicular cells (also known as C cells) of the thyroid gland.
2. Pheochromocytomas: These are tumors that develop in the adrenal glands, usually in the chromaffin cells. They can cause the release of excessive amounts of catecholamines, leading to hypertension and other symptoms. Approximately 50% of MEN 2A patients will develop pheochromocytomas.
3. Primary Parathyroid Hyperplasia or Adenomas: Overactivity of the parathyroid glands can lead to hyperparathyroidism, which results in increased calcium levels in the blood (hypercalcemia). This occurs in about 20% of MEN 2A patients.
MEN 2A is an autosomal dominant disorder, meaning that if one parent has the condition, there is a 50% chance their offspring will inherit the mutated gene and develop the disease. Early detection and treatment of the associated tumors can significantly improve patient outcomes.
Endothelin receptors are a type of G protein-coupled receptor that bind to endothelin, a potent vasoconstrictor peptide. There are two main types of endothelin receptors: ETA and ETB. ETA receptors are found in vascular smooth muscle cells and activate phospholipase C, leading to an increase in intracellular calcium and subsequent contraction of the smooth muscle. ETB receptors are found in both endothelial cells and vascular smooth muscle cells. In endothelial cells, ETB receptor activation leads to the release of nitric oxide and prostacyclin, which cause vasodilation. In vascular smooth muscle cells, ETB receptor activation causes vasoconstriction through a mechanism that is not fully understood.
Endothelin receptors play important roles in regulating blood flow, vascular remodeling, and the development of cardiovascular diseases such as hypertension and heart failure. They are also involved in the regulation of cell growth, differentiation, and apoptosis in various tissues.
"Facies" is a medical term that refers to the typical appearance of a person or part of the body, particularly the face, which may provide clues about their underlying medical condition or genetic background. A specific facies is often associated with certain syndromes or disorders. For example, a "downsyndrome facies" refers to the distinctive facial features commonly found in individuals with Down syndrome, such as a flattened nasal bridge, almond-shaped eyes, and an upward slant to the eyelids.
It's important to note that while facies can provide valuable diagnostic information, it should be used in conjunction with other clinical findings and genetic testing to make a definitive diagnosis. Additionally, facies should be described objectively and without judgment, as they are simply physical characteristics associated with certain medical conditions.
Penetrance, in medical genetics, refers to the proportion of individuals with a particular genetic variant or mutation who exhibit clinical features or symptoms of a resulting disease. It is often expressed as a percentage, with complete penetrance indicating that all individuals with the genetic change will develop the disease, and reduced or incomplete penetrance suggesting that not all individuals with the genetic change will necessarily develop the disease, even if they express some of its characteristics.
Penetrance can vary depending on various factors such as age, sex, environmental influences, and interactions with other genes. Incomplete penetrance is common in many genetic disorders, making it challenging to predict who will develop symptoms based solely on their genotype.
A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.
Medullary carcinoma is a type of cancer that develops in the neuroendocrine cells of the thyroid gland. These cells produce hormones that help regulate various bodily functions. Medullary carcinoma is a relatively rare form of thyroid cancer, accounting for about 5-10% of all cases.
Medullary carcinoma is characterized by the presence of certain genetic mutations that cause the overproduction of calcitonin, a hormone produced by the neuroendocrine cells. This overproduction can lead to the formation of tumors in the thyroid gland.
Medullary carcinoma can be hereditary or sporadic. Hereditary forms of the disease are caused by mutations in the RET gene and are often associated with multiple endocrine neoplasia type 2 (MEN 2), a genetic disorder that affects the thyroid gland, adrenal glands, and parathyroid glands. Sporadic forms of medullary carcinoma, on the other hand, are not inherited and occur randomly in people with no family history of the disease.
Medullary carcinoma is typically more aggressive than other types of thyroid cancer and tends to spread (metastasize) to other parts of the body, such as the lymph nodes, lungs, and liver. Symptoms may include a lump or nodule in the neck, difficulty swallowing, hoarseness, and coughing. Treatment options may include surgery, radiation therapy, and chemotherapy. Regular monitoring of calcitonin levels is also recommended to monitor the effectiveness of treatment and detect any recurrence of the disease.
High mobility group proteins (HMG proteins) are a family of nuclear proteins that are characterized by their ability to bind to DNA and influence its structure and function. They are named "high mobility" because of their rapid movement in gel electrophoresis. HMG proteins are involved in various nuclear processes, including chromatin remodeling, transcription regulation, and DNA repair.
There are three main classes of HMG proteins: HMGA, HMGB, and HMGN. Each class has distinct structural features and functions. For example, HMGA proteins have a unique "AT-hook" domain that allows them to bind to the minor groove of AT-rich DNA sequences, while HMGB proteins have two "HMG-box" domains that enable them to bend and unwind DNA.
HMG proteins play important roles in many physiological and pathological processes, such as embryonic development, inflammation, and cancer. Dysregulation of HMG protein function has been implicated in various diseases, including neurodegenerative disorders, diabetes, and cancer. Therefore, understanding the structure, function, and regulation of HMG proteins is crucial for developing new therapeutic strategies for these diseases.
Consanguinity is a medical and genetic term that refers to the degree of genetic relationship between two individuals who share common ancestors. Consanguineous relationships exist when people are related by blood, through a common ancestor or siblings who have children together. The closer the relationship between the two individuals, the higher the degree of consanguinity.
The degree of consanguinity is typically expressed as a percentage or fraction, with higher values indicating a closer genetic relationship. For example, first-degree relatives, such as parents and children or full siblings, share approximately 50% of their genes and have a consanguinity coefficient of 0.25 (or 25%).
Consanguinity can increase the risk of certain genetic disorders and birth defects in offspring due to the increased likelihood of sharing harmful recessive genes. The risks depend on the degree of consanguinity, with closer relationships carrying higher risks. It is important for individuals who are planning to have children and have a history of consanguinity to consider genetic counseling and testing to assess their risk of passing on genetic disorders.
The rectum is the lower end of the digestive tract, located between the sigmoid colon and the anus. It serves as a storage area for feces before they are eliminated from the body. The rectum is about 12 cm long in adults and is surrounded by layers of muscle that help control defecation. The mucous membrane lining the rectum allows for the detection of stool, which triggers the reflex to have a bowel movement.
'Abnormalities, Multiple' is a broad term that refers to the presence of two or more structural or functional anomalies in an individual. These abnormalities can be present at birth (congenital) or can develop later in life (acquired). They can affect various organs and systems of the body and can vary greatly in severity and impact on a person's health and well-being.
Multiple abnormalities can occur due to genetic factors, environmental influences, or a combination of both. Chromosomal abnormalities, gene mutations, exposure to teratogens (substances that cause birth defects), and maternal infections during pregnancy are some of the common causes of multiple congenital abnormalities.
Examples of multiple congenital abnormalities include Down syndrome, Turner syndrome, and VATER/VACTERL association. Acquired multiple abnormalities can result from conditions such as trauma, infection, degenerative diseases, or cancer.
The medical evaluation and management of individuals with multiple abnormalities depend on the specific abnormalities present and their impact on the individual's health and functioning. A multidisciplinary team of healthcare professionals is often involved in the care of these individuals to address their complex needs.
Intellectual disability (ID) is a term used when there are significant limitations in both intellectual functioning and adaptive behavior, which covers many everyday social and practical skills. This disability originates before the age of 18.
Intellectual functioning, also known as intelligence, refers to general mental capacity, such as learning, reasoning, problem-solving, and other cognitive skills. Adaptive behavior includes skills needed for day-to-day life, such as communication, self-care, social skills, safety judgement, and basic academic skills.
Intellectual disability is characterized by below-average intelligence or mental ability and a lack of skills necessary for day-to-day living. It can be mild, moderate, severe, or profound, depending on the degree of limitation in intellectual functioning and adaptive behavior.
It's important to note that people with intellectual disabilities have unique strengths and limitations, just like everyone else. With appropriate support and education, they can lead fulfilling lives and contribute to their communities in many ways.
'Drosophila proteins' refer to the proteins that are expressed in the fruit fly, Drosophila melanogaster. This organism is a widely used model system in genetics, developmental biology, and molecular biology research. The study of Drosophila proteins has contributed significantly to our understanding of various biological processes, including gene regulation, cell signaling, development, and aging.
Some examples of well-studied Drosophila proteins include:
1. HSP70 (Heat Shock Protein 70): A chaperone protein involved in protein folding and protection from stress conditions.
2. TUBULIN: A structural protein that forms microtubules, important for cell division and intracellular transport.
3. ACTIN: A cytoskeletal protein involved in muscle contraction, cell motility, and maintenance of cell shape.
4. BETA-GALACTOSIDASE (LACZ): A reporter protein often used to monitor gene expression patterns in transgenic flies.
5. ENDOGLIN: A protein involved in the development of blood vessels during embryogenesis.
6. P53: A tumor suppressor protein that plays a crucial role in preventing cancer by regulating cell growth and division.
7. JUN-KINASE (JNK): A signaling protein involved in stress response, apoptosis, and developmental processes.
8. DECAPENTAPLEGIC (DPP): A member of the TGF-β (Transforming Growth Factor Beta) superfamily, playing essential roles in embryonic development and tissue homeostasis.
These proteins are often studied using various techniques such as biochemistry, genetics, molecular biology, and structural biology to understand their functions, interactions, and regulation within the cell.
Proto-oncogene proteins are normal cellular proteins that play crucial roles in various cellular processes, such as signal transduction, cell cycle regulation, and apoptosis (programmed cell death). They are involved in the regulation of cell growth, differentiation, and survival under physiological conditions.
When proto-oncogene proteins undergo mutations or aberrations in their expression levels, they can transform into oncogenic forms, leading to uncontrolled cell growth and division. These altered proteins are then referred to as oncogene products or oncoproteins. Oncogenic mutations can occur due to various factors, including genetic predisposition, environmental exposures, and aging.
Examples of proto-oncogene proteins include:
1. Ras proteins: Involved in signal transduction pathways that regulate cell growth and differentiation. Activating mutations in Ras genes are found in various human cancers.
2. Myc proteins: Regulate gene expression related to cell cycle progression, apoptosis, and metabolism. Overexpression of Myc proteins is associated with several types of cancer.
3. EGFR (Epidermal Growth Factor Receptor): A transmembrane receptor tyrosine kinase that regulates cell proliferation, survival, and differentiation. Mutations or overexpression of EGFR are linked to various malignancies, such as lung cancer and glioblastoma.
4. Src family kinases: Intracellular tyrosine kinases that regulate signal transduction pathways involved in cell proliferation, survival, and migration. Dysregulation of Src family kinases is implicated in several types of cancer.
5. Abl kinases: Cytoplasmic tyrosine kinases that regulate various cellular processes, including cell growth, differentiation, and stress responses. Aberrant activation of Abl kinases, as seen in chronic myelogenous leukemia (CML), leads to uncontrolled cell proliferation.
Understanding the roles of proto-oncogene proteins and their dysregulation in cancer development is essential for developing targeted cancer therapies that aim to inhibit or modulate these aberrant signaling pathways.
A haplotype is a group of genes or DNA sequences that are inherited together from a single parent. It refers to a combination of alleles (variant forms of a gene) that are located on the same chromosome and are usually transmitted as a unit. Haplotypes can be useful in tracing genetic ancestry, understanding the genetic basis of diseases, and developing personalized medical treatments.
In population genetics, haplotypes are often used to study patterns of genetic variation within and between populations. By comparing haplotype frequencies across populations, researchers can infer historical events such as migrations, population expansions, and bottlenecks. Additionally, haplotypes can provide information about the evolutionary history of genes and genomic regions.
In clinical genetics, haplotypes can be used to identify genetic risk factors for diseases or to predict an individual's response to certain medications. For example, specific haplotypes in the HLA gene region have been associated with increased susceptibility to certain autoimmune diseases, while other haplotypes in the CYP450 gene family can affect how individuals metabolize drugs.
Overall, haplotypes provide a powerful tool for understanding the genetic basis of complex traits and diseases, as well as for developing personalized medical treatments based on an individual's genetic makeup.
A germ-line mutation is a genetic change that occurs in the egg or sperm cells (gametes), and thus can be passed down from parents to their offspring. These mutations are present throughout the entire body of the offspring, as they are incorporated into the DNA of every cell during embryonic development.
Germ-line mutations differ from somatic mutations, which occur in other cells of the body that are not involved in reproduction. While somatic mutations can contribute to the development of cancer and other diseases within an individual, they are not passed down to future generations.
It's important to note that germ-line mutations can have significant implications for medical genetics and inherited diseases. For example, if a parent has a germ-line mutation in a gene associated with a particular disease, their offspring may have an increased risk of developing that disease as well.
Nerve Growth Factors (NGFs) are a family of proteins that play an essential role in the growth, maintenance, and survival of certain neurons (nerve cells). They were first discovered by Rita Levi-Montalcini and Stanley Cohen in 1956. NGF is particularly crucial for the development and function of the peripheral nervous system, which connects the central nervous system to various organs and tissues throughout the body.
NGF supports the differentiation and survival of sympathetic and sensory neurons during embryonic development. In adults, NGF continues to regulate the maintenance and repair of these neurons, contributing to neuroplasticity – the brain's ability to adapt and change over time. Additionally, NGF has been implicated in pain transmission and modulation, as well as inflammatory responses.
Abnormal levels or dysfunctional NGF signaling have been associated with various medical conditions, including neurodegenerative diseases (e.g., Alzheimer's and Parkinson's), chronic pain disorders, and certain cancers (e.g., small cell lung cancer). Therefore, understanding the role of NGF in physiological and pathological processes may provide valuable insights into developing novel therapeutic strategies for these conditions.
A syndrome, in medical terms, is a set of symptoms that collectively indicate or characterize a disease, disorder, or underlying pathological process. It's essentially a collection of signs and/or symptoms that frequently occur together and can suggest a particular cause or condition, even though the exact physiological mechanisms might not be fully understood.
For example, Down syndrome is characterized by specific physical features, cognitive delays, and other developmental issues resulting from an extra copy of chromosome 21. Similarly, metabolic syndromes like diabetes mellitus type 2 involve a group of risk factors such as obesity, high blood pressure, high blood sugar, and abnormal cholesterol or triglyceride levels that collectively increase the risk of heart disease, stroke, and diabetes.
It's important to note that a syndrome is not a specific diagnosis; rather, it's a pattern of symptoms that can help guide further diagnostic evaluation and management.
I must clarify that the term "pedigree" is not typically used in medical definitions. Instead, it is often employed in genetics and breeding, where it refers to the recorded ancestry of an individual or a family, tracing the inheritance of specific traits or diseases. In human genetics, a pedigree can help illustrate the pattern of genetic inheritance in families over multiple generations. However, it is not a medical term with a specific clinical definition.
Single-Stranded Conformational Polymorphism (SSCP) is not a medical condition but rather a laboratory technique used in molecular biology and genetics. It refers to the phenomenon where a single-stranded DNA or RNA molecule can adopt different conformations or shapes based on its nucleotide sequence, even if the difference in the sequence is as small as a single base pair change. This property is used in SSCP analysis to detect mutations or variations in DNA or RNA sequences.
In SSCP analysis, the denatured single-stranded DNA or RNA sample is subjected to electrophoresis on a non-denaturing polyacrylamide gel. The different conformations of the single-stranded molecules migrate at different rates in the gel, creating multiple bands that can be visualized by staining or other detection methods. The presence of additional bands or shifts in band patterns can indicate the presence of a sequence variant or mutation.
SSCP analysis is often used as a screening tool for genetic diseases, cancer, and infectious diseases to identify genetic variations associated with these conditions. However, it has largely been replaced by more sensitive and accurate methods such as next-generation sequencing.
Hirschsprung's disease
Hirschsprung's disease-type D brachydactyly syndrome
Harald Hirschsprung
Heinrich Hirschsprung
Chronic diarrhea of infancy
Orvar Swenson
Pull-through procedure
Intestinal pseudo-obstruction
13q deletion syndrome
Endothelin 3
Glial cell line-derived neurotrophic factor
Frederik Ruysch
Yemenite deaf-blind hypopigmentation syndrome
Kavain
Myenteric plexus
Desmosis
Endothelin receptor type B
Lethal white syndrome
Patricia Flint Borns
RASGEF1A
Patricia Baird
SOX10
HOXD9
Al-Gazali-Donnai-Mueller syndrome
Goldberg-Shprintzen syndrome
Neuregulin 3
GFRA1
HOXA4
Multiple endocrine neoplasia type 2
AEBP2
Hirschsprung's disease - Wikipedia
Hirschsprung disease: MedlinePlus Genetics
Hirschsprung Disease: Background, Pathophysiology, Epidemiology
Hirschsprung Disease Medication: Antibiotics, Toxins
Hirschsprung Disease - Symptoms, Causes, Treatment | NORD
Hirschsprung Disease Imaging: Practice Essentials, Radiography, Ultrasonography
Man's 29 Lbs. of Poop Removed: What Is Hirschsprung's Disease? | Live Science
Hirschsprung's Disease
Mowat Wilson syndrome and Hirschsprung disease: a retrospective study on functional outcomes
Hirschsprung Disease Archives - Genetic Support Network Victoria (GSNV)
Hirschsprung's disease Archives - Genetic Support Network Victoria (GSNV)
Interstitial deletion of distal 13q associated with Hirschsprung's disease. | Journal of Medical Genetics
Adult patients with allied disorders of Hirschsprung's disease in emergency department: An 11-year retrospective study
Hirschsprung's Disease and Allied Disorders, Third Edition edited by Alexander M. Holschneider, Prem Puri
Transanal Swenson's operation for Rectosigmoid Hirschsprung's disease | African Journal of Paediatric Surgery
Hirschsprung disease
hirschsprung's disease Archives - The Quinnipiac Chronicle
Surgical treatment of Hirschsprung's disease at the National Children's Hospital "Dr. Carlos Saenz Herrera" during the period...
Hirschsprung's disease - wikidoc
Hirschsprung Disease in Children
Hirschsprung disease-Birth Defects - Healthviber
Open Proctocolectomy for Hirschsprung's Disease | JOMI
Hirschsprung's disease: Difference between revisions - WikEM
Hirschsprung Disease - Pediatrics - MSD Manual Professional Edition
Genetics in Hirschsprung Disease - Practical Gastro
Hirschsprung's Disease Symptoms, Diagnosis, Causes, Treatment
Hirschsprung disease type 3 | Rare Diseases | RareGuru
Genetic Analysis of Hirschsprung Disease | NYU Langone Health
Waardenburg syndrome with Hirschsprung disease | Hereditary Ocular Diseases
Hirschsprung's110
- Hirschsprung's disease (HD or HSCR) is a birth defect in which nerves are missing from parts of the intestine. (wikipedia.org)
- About half of all children with Hirschsprung's disease are diagnosed in the first year of life. (wikipedia.org)
- Hirschsprung's disease occurs in about one in 5,000 of newborns. (wikipedia.org)
- Hirschsprung's disease can also present as part of multi system disorders, such as: Bardet-Biedl syndrome Cartilage-hair hypoplasia Congenital central hypoventilation syndrome MEN2 Mowat-Wilson syndrome Smith-Lemli-Opitz syndrome Trisomy 21 (Down syndrome) Some forms of Waardenburg syndrome The disorder may occur by itself or in association with other genetic disorders such as Down syndrome. (wikipedia.org)
- Several genes and specific regions on chromosomes (loci) have been shown or suggested to be associated with Hirschsprung's disease: The RET proto-oncogene accounts for the highest proportion of both familial and sporadic cases, with a wide range of mutations scattered along its entire coding region. (wikipedia.org)
- Research suggests that several genes are associated with Hirschsprung's disease. (wikipedia.org)
- Also, new research suggests that mutations in genomic sequences involved in regulating EDNRB have a bigger impact on Hirschsprung's disease than previously thought. (wikipedia.org)
- Heanue TA, Pachnis V. Enteric nervous system development and Hirschsprung's disease: advances in genetic and stem cell studies. (medscape.com)
- Okamoto E, Takashi U. Embryogenesis of intramural ganglia of the gut and its relation to Hirschsprung's disease. (medscape.com)
- Langer JC, Betti PA, Blennerhassett MG. Smooth muscle from aganglionic bowel in Hirschsprung's disease impairs neuronal development in vitro. (medscape.com)
- The research on screening differentially expressed genes in Hirschsprung's disease by using Microarray. (medscape.com)
- Electrophysiological properties of the aganglionic segment in Hirschsprung's disease. (medscape.com)
- Man's 29 Lbs. of Poop Removed: What Is Hirschsprung's Disease? (livescience.com)
- The man had a very rare condition called Hirschsprung's disease, the website Inverse reported. (livescience.com)
- Hirschsprung's disease is a birth defect that affects about 1 in 5,000 babies in the U.S., according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD). (livescience.com)
- In those with Hirschsprung's disease, the nerves do not reach the end of the bowel. (livescience.com)
- The most obvious sign that a newborn has Hirschsprung's disease is that the baby does not have a bowel movement within the first 48 hours after birth, the Mayo Clinic sa ys. (livescience.com)
- A key difference is that in infants or children with Hirschsprung's disease, constipation drugs taken by mouth, such as laxatives, typically do not have an effect, the NIDDKD says. (livescience.com)
- The only treatment for Hirschsprung's disease is surgery to remove the defective part of the colon, according to the NIDDKD. (livescience.com)
- Rarely, Hirschsprung's disease remains undiagnosed until a person reaches adulthood. (livescience.com)
- Hirschsprung's (HIRSH-sproongz) disease is a condition that affects the large intestine (colon) and causes problems with passing stool. (sparrow.org)
- A newborn who has Hirschsprung's disease usually can't have a bowel movement in the days after birth. (sparrow.org)
- Uncommonly, Hirschsprung's disease is first diagnosed in adults. (sparrow.org)
- Signs and symptoms of Hirschsprung's disease vary with the severity of the condition. (sparrow.org)
- It's not clear what causes Hirschsprung's disease. (sparrow.org)
- Hirschsprung's disease occurs when nerve cells in the colon don't form completely. (sparrow.org)
- Having a sibling who has Hirschsprung's disease. (sparrow.org)
- Hirschsprung's disease can be inherited. (sparrow.org)
- Hirschsprung's disease is more common in males. (sparrow.org)
- Hirschsprung's disease is associated with certain inherited conditions, such as Down syndrome and other abnormalities present at birth, such as congenital heart disease. (sparrow.org)
- Children who have Hirschsprung's disease are prone to a serious intestinal infection called enterocolitis. (sparrow.org)
- This is the surest way to identify Hirschsprung's disease. (sparrow.org)
- If it doesn't, Hirschsprung's disease could be the cause. (sparrow.org)
- For most people, Hirschsprung's disease is treated with surgery to bypass or remove the part of the colon that's lacking nerve cells. (sparrow.org)
- Hirschsprung's disease is the most common cause of lower intestinal obstruction in neonates. (tutorialspoint.com)
- Hirschsprung's disease is suspected in a baby who has not passed meconium within 48 hours of birth. (tutorialspoint.com)
- Interstitial deletion of distal 13q associated with Hirschsprung's disease. (bmj.com)
- In addition to the recognised clinical features of this deletion, two had Hirschsprung's disease. (bmj.com)
- Association of 13q deletion and Hirschsprung's disease. (bmj.com)
- Hirschsprung's Disease and Allied Disorders is the third edition of a comprehensive study of the neuronal disorders of the lower gastrointestinal tract in children. (chipsbooks.com)
- Background: Transanal Swenson's operation is a relatively new single-stage procedure for Hirschsprung's disease. (ajol.info)
- Patients and Methods: Seventeen patients of recto-sigmoid Hirschsprung's disease underwent single-stage transanal Swenson's procedure. (ajol.info)
- the clinical and epidemiological characteristics of the cases of Hirschsprung's Disease analyzed are similar to those reported in the literature. (scielo.sa.cr)
- Hirschsprung's disease is a congenital disorder characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the intestine. (scielo.sa.cr)
- Early diagnosis and management avoids the potential complications of patients with Hirschsprung's disease. (scielo.sa.cr)
- Upon approval of the study by the institutional bioethics committee, the medical records were reviewed as population taking all patients discharged from the National Children's Hospital diagnosed with Hirschsprung's disease from January 2000 to December 2010. (scielo.sa.cr)
- Patients with the diagnosis of Hirschsprung's disease were included during the established term, who had undergone surgery. (scielo.sa.cr)
- Cases with incomplete records and all patients who had Hirschsprung's disease ruled out were excluded from the analysis. (scielo.sa.cr)
- Hirschsprung's disease (HD) is due to a congenital absence of ganglion cells (aganglionosis) in the colon leading to difficult-to-treat constipation as well as the potential for life-threatening enterocolitis from colonic inflammation. (practicalgastro.com)
- Hirschsprung's disease in adults, infants. (healthncare.info)
- Hirschsprung's disease diet and radiology. (healthncare.info)
- Hirschsprung's disease is congenital (present when a baby is born) and results from missing nerve cells in the muscles of part or the baby's entire colon. (healthncare.info)
- A newborn that has Hirschsprung's disease is usually unable to have a bowel movement in the first days after birth. (healthncare.info)
- With Hirschsprung's disease, the nerve cells stop growing too soon. (healthncare.info)
- Some Hirschsprung's disease is inherited, meaning it is passed from parent to child through genes. (healthncare.info)
- Hirschsprung's disease is not caused by anything a mother did while pregnant. (healthncare.info)
- Approximately 20 percent of cases of Hirschsprung's disease occur in multiple members of the same family. (healthncare.info)
- Children with Down syndrome and genetic heart conditions also have an increased risk of Hirschsprung's disease. (healthncare.info)
- Hirschsprung's disease is diagnosed based on symptoms and test results. (healthncare.info)
- Hirschsprung's disease is much less likely if parents can identify a time when their child's bowel habits were normal. (healthncare.info)
- To diagnose Hirschsprung's disease, doctors often do a test called a barium enema. (healthncare.info)
- If the muscles do not relax, Hirschsprung's disease may be the problem. (healthncare.info)
- Biopsy is the most accurate test for Hirschsprung's disease. (healthncare.info)
- If nerve cells are missing, Hirschsprung's disease is diagnosed. (healthncare.info)
- Surgery is thought to be the most effective treatment for Hirschsprung's disease. (healthncare.info)
- Hirschsprung's disease is treated with surgery called a pull-through procedure. (healthncare.info)
- Hirschsprung's disease (HD, congenital aganglionic megacolon) is a disorder due to the absence of enteric ganglion cells due to the failure of the neural crest cells during development. (jomi.com)
- Hirschsprung's disease: Enlargement of the colon, caused by bowel obstruction resulting from an aganglionic section of bowel (the normal enteric nerves are absent). (nurseslabs.com)
- In 1886, Harold Hirschsprung first described Hirschsprung's disease as a cause of constipation in early infancy. (nurseslabs.com)
- Primary laparoscopic-assisted endorectal colon pull-through for Hirschsprung's disease: a new gold standard. (qxmd.com)
- To describe the surgical technique and early clinical results after a one-stage laparoscopic-assisted endorectal colon pull-through for Hirschsprung's disease. (qxmd.com)
- Recent trends in surgery for Hirschsprung's disease have been toward earlier repair and fewer surgical stages. (qxmd.com)
- A one-stage pull-through for Hirschsprung's disease avoids the additional anesthesia, surgery, and complications of a colostomy. (qxmd.com)
- Traditionally Hirschsprung's disease has been treated by 2-or 3-stage procedures. (tau.ac.il)
- During the past 6 years a 1-stage Duhamel procedure without stoma has become our treatment of choice for Hirschsprung's disease in neonates and young infants. (tau.ac.il)
- Over a 6-year period, 15 infants and children with colonie Hirschsprung's disease were treated with the 1-stage Duhamel retro-rectal pull-through procedure without a stoma, with the Lester-Martin modification. (tau.ac.il)
- We conclude that Hirschsprung's disease can be successfully treated with a 1-stage pull-through operation, the child usually benefitting from the shorter hospital stay and the avoidance of a colostomy. (tau.ac.il)
- Mutation analysis of the RET, the endothelin-B receptor, and the endothelin-3 genes in sporadic cases of Hirschsprung's disease. (drugbank.com)
- To date, three genes have been identified as susceptibility genes for Hirschsprung's disease (HSCR), the RET proto-oncogene, the endothelin-B receptor gene (EDNRB) and the endothelin-3 gene (EDN3). (drugbank.com)
- In order to better address and clarify the feasibility of robotic surgery in this specific subset of patients, we will present a series of 30 patients who underwent robotic surgery for either primary or reiterative surgery in Hirschsprung's disease between 2017 and 2021 (5 year period). (eurogen-ern.eu)
- What is Hirschsprung's disease? (pediatricsurgicalcare.com)
- Hirschsprung's disease is a congenital (present at birth) disease of the large intestine in which there is an absence of special nerve cells - called ganglion cells - that affect the muscles in the intestine. (pediatricsurgicalcare.com)
- If Hirschsprung's disease is not treated, stool can back up in the large intestine, which can lead to serious problems such as infection and bursting of the intestine. (pediatricsurgicalcare.com)
- How is Hirschsprung's disease treated? (pediatricsurgicalcare.com)
- Surgery - The definitive surgery for Hirschsprung's disease involves removing the part of the large intestine without ganglion cells and replacing it with part of the large intestine that has the normal number of cells. (pediatricsurgicalcare.com)
- What is the outlook for people with Hirschsprung's disease? (pediatricsurgicalcare.com)
- What Are the Treatments for Hirschsprung's Disease? (arnoldpalmerhospital.com)
- Children with Hirschsprung's disease need surgery to remove the part of the colon that is missing nerve cells. (arnoldpalmerhospital.com)
- This can often be done with minimally invasive techniques right after Hirschsprung's disease is diagnosed. (arnoldpalmerhospital.com)
- Surgery for Hirschsprung's disease usually leads to excellent outcomes, and children have no lasting complications. (arnoldpalmerhospital.com)
- While most children do well after surgery, Hirschsprung's disease makes them more likely to develop a serious infection called enterocolitis. (arnoldpalmerhospital.com)
- 09.50 Utilising the zebra fish to identify genes whose defects result in Hirschsprung's Disease - Tiffany Heanue , Crick Institute, London. (baps.org.uk)
- 11.30 Hirschsprung's Disease - consideration and planning for transition. (baps.org.uk)
- To whomever may be reading this, I am a thirteen year old girl born with short segment Hirschsprung's disease. (teenhealthfx.com)
- Hirschsprung's disease is a chronic illness which flairs up got no reason some times and can cause abdominal pain. (teenhealthfx.com)
- My biggest question, is whether Hirschsprung's Disease can cause Urinary Incontonence. (teenhealthfx.com)
- In case other readers are not aware, Hirschsprung's disease is a disease commonly found in infants but may not be found until children are older. (teenhealthfx.com)
- Hirschsprung's disease is not typically associated with urinary incontinence with the exception of surgical or other procedure complications. (teenhealthfx.com)
- Outcome of single-stage transanal endorectal pull through for short segment Hirschsprung's disease in neonates and infants. (bvsalud.org)
- Hirschsprung's disease (HD) is developmental disorder of the enteric nervous system . (bvsalud.org)
- Background: Several genes, including the major susceptibility gene RET, have roles in development of Hirschsprung's disease. (uni-luebeck.de)
- We aimed to investigate whether both RET mutations and polymorphisms contribute to phenotype of Hirschsprung's disease. (uni-luebeck.de)
- Methods: We looked at the coding region of all 21 exons of the RET proto-oncogene, including the flanking intronic sequences, by direct DNA sequencing in 76 caucasians from Germany with Hirschsprung's disease. (uni-luebeck.de)
- Interpretation: These observations lend support to the idea that both RET alleles have a role in pathogenesis of Hirschsprung's disease, in a dose-dependent fashion. (uni-luebeck.de)
- A child with Hirschsprung's disease use a nurse to gain ego strenght. (bvsalud.org)
- Background: Hirschsprung's disease (HD) is a common cause of intestinal obstruction in children. (bvsalud.org)
- The ITGB2 immunomodulatory gene (CD18), enterocolitis, and Hirschsprung's disease. (lu.se)
- DS patients may also exhibit congenital heart disease between 40 and 50% of the cases an increased risk for developing Alzheimer's disease, acute megakaryocytic leukemia, Hirschsprung's disease and duodenal atresia. (bvsalud.org)
- The purpose of this project is to develop, evaluate and implement novel bioimaging techniques for monitoring perfusion and oxygenation during pediatric surgery, with regard to congenital anorectal malformations, Hirschsprung's disease and tumors, and to assess the correlation to postoperative complications in the skin and intestine. (lu.se)
- Every year, about 100 children undergo surgery with reconstruction of the rectum, pelvic floor and genitals due to malformations of the gastrointestinal tract such as anal atresia, Hirschsprung's disease, esophageal atresia, or urogenital malformations such as hypospadias, and congenital pelvic tumors such as sacrococcygeal teratoma. (lu.se)
Aganglionosis4
- Although this condition was described by Ruysch in 1691 and popularized by Hirschsprung in 1886, the pathophysiology was not clearly determined until the middle of the 20th century, when Whitehouse and Kernohan reported aganglionosis of the distal colon as the cause of obstruction in a case series. (medscape.com)
- Hirschsprung Disease (HD) adalah kelainan kongenital dimana tidak dijumpai sel ganglion persyarafan (aganglionosis plexus Meissner & Auerbachs) pada distal kolon dan dapat. (radiologi.id)
- Hirschsprung disease is caused by congenital absence of the Meissner and Auerbach autonomic plexus (aganglionosis) in the intestinal wall. (msdmanuals.com)
- Hirschsprung disease, which consists of aganglionosis of the rectum and sometimes more proximal bowel, requires surgical removal of the aganglionic bowel and creation of ganglionated neorectum using proximal normally innervated bowel. (qxmd.com)
Congenital megacolon2
- Hirschsprung´s disease (congenital megacolon ) is a common cause of lower bowel obstruction in neonates. (scielo.sa.cr)
- There are various types of megacolon including congenital megacolon in HIRSCHSPRUNG DISEASE, idiopathic megacolon in CONSTIPATION, and TOXIC MEGACOLON. (bvsalud.org)
Associated with Hirschsprung disease include2
- Other disorders associated with Hirschsprung disease include Waardenburg syndrome, Bardet-Biedl syndrome, Goldberg-Shprintzen syndrome, and cartilage-hair hypoplasia. (msdmanuals.com)
- other genes associated with Hirschsprung disease include the glial cell-derived neurotrophic factor gene, the endothelin-B receptor gene, and the endothelin-3 gene. (nurseslabs.com)
Etiology3
- [ 3 ] One possible etiology of Hirschsprung disease is the arrest of aboral neuroblast migration. (medscape.com)
- The developmental etiology and pathogenesis of Hirschsprung disease. (medscape.com)
- Until the early 1970s, a bacterial, viral, or parasitic etiology of diarrheal disease in children could be detected in fewer than 30% of cases. (cdc.gov)
Enterocolitis7
- Enterocolitis, an acute complication of Hirschsprung disease, is characterised by sudden onset of fever, abdominal distension, vomiting, passage of bloody stools or release of explosive gas or stools after rectal examination. (wikipedia.org)
- This is often referred to as Hirschsprung-associated enterocolitis. (rarediseases.org)
- Hirschsprung-associated enterocolitis is the most frequent complication of HSCR occurring in 30-40% of individuals with HSCR and can be mild to severe in nature. (rarediseases.org)
- Some individuals with either severe or untreated Hirschsprung-associated enterocolitis may develop sepsis, which is a widespread bacterial infection of the bloodstream and is potentially life-threatening. (rarediseases.org)
- People with this disorder are at risk of developing more serious conditions such as inflammation of the intestine (enterocolitis) or a hole in the wall of the intestine (intestinal perforation), which can cause serious infection and may be fatal.There are two main types of Hirschsprung disease, known as short-segment disease and long-segment disease, which are defined by the region of the intestine lacking nerve cells. (healthviber.com)
- Early recognition and surgical correction of Hirschsprung disease protect affected infants from enterocolitis and debilitating constipation. (nurseslabs.com)
- The overall mortality of Hirschsprung enterocolitis is 25-30%, which accounts for almost all of the mortality from Hirschsprung disease. (nurseslabs.com)
Surgical5
- More recently, earlier diagnosis and advances in surgical techniques have resulted in decreased morbidity and mortality in patients with Hirschsprung disease. (medscape.com)
- MWS associated with Hirschsprung disease has a high rate of immediate surgical complications but some patients may achieve bowel function comparable with non-syndromic HD patients. (nih.gov)
- 5-9 Disease management has evolved over the years from very invasive procedures performed in several stages including three surgeries, to minimally invasive procedures carried out in a single surgical intervention. (scielo.sa.cr)
- Although there are multiple causes for poor outcomes following surgical therapy for Hirschsprung disease, abnormal innervation of the bowel used for pull-through is common. (qxmd.com)
- Pre-surgical image of dilated colon due to Hirshprungs disease. (lu.se)
Diagnosis1
- For this procedure, the level at which the normal functioning bowel occurs is determined at the time of the operation with the assistance of gastrointestinal (GI) pathologists, doctors who studies cells and tissues to identify diseases and help with diagnosis. (pediatricsurgicalcare.com)
Birth defect1
- Hirschsprung disease (HSCR) is a birth defect. (rarediseases.org)
Genes5
- Isolated Hirschsprung disease can result from mutations in one of several genes, including the RET , EDNRB , and EDN3 genes. (medlineplus.gov)
- Hirschsprung disease that occurs as an isolated problem has been associated with mutations in several different genes. (rarediseases.org)
- A person who is genetically predisposed to a disorder carries a gene (or genes) for the disease, but it may not be expressed unless it is triggered or "activated" under certain circumstances, such as due to particular environmental factors (multifactorial inheritance). (rarediseases.org)
- However, the low mutation rate of susceptibility genes in sporadically occurring HSCR suggests that other genes or environmental factors are involved in the development of the disease. (drugbank.com)
- Many susceptibility genes including RET, the major HSCR gene, and several linked regions and associated loci have been shown to contribute to disease pathogenesis. (unige.it)
Mutations4
- Mutations in the RET gene are the most common known genetic cause of Hirschsprung disease. (medlineplus.gov)
- Mutations in the RET gene that cause Hirschsprung disease result in a nonfunctional version of the RET protein that cannot transmit signals within cells. (medlineplus.gov)
- Functional analyses of RET mutations in Chinese Hirschsprung disease patients. (medscape.com)
- There is a significant genetic component to this disorder, and at least 12 different genetic mutations are associated with Hirschsprung. (msdmanuals.com)
Syndrome8
- Hirschsprung disease is sometimes linked to other inherited or congenital conditions, such as Down syndrome. (adam.com)
- We don't have a description for this disease, disorder, or syndrome yet. (rareguru.com)
- Do you have information about a disease, disorder, or syndrome? (rareguru.com)
- Type 4 Waardenburg syndrome is largely similar to other types except that many patients also have Hirschsprung disease. (arizona.edu)
- I had heard of down syndrome of course (being a PT, it is part of the training) but Hirschsprung disease was something totally new. (livelifelakshsize.com)
- For example, about one in 100 children with Down syndrome also has Hirschsprung disease. (livelifelakshsize.com)
- Many cutaneous disorders experienced by patients undergoing dialysis have little to do with the uremic syndrome and are related to the same underlying pathologic process that caused the renal disease. (medscape.com)
- Down Syndrome (DS) patients have increased susceptibility to the development of periodontal diseases by the occurrence of several factors, such as inadequate hygiene, mouth breathing, dental morphology, leukocyte reduction and increased inflammatory mediators. (bvsalud.org)
Large intestine6
- In short-segment disease, nerve cells are missing from only the last segment of the large intestine (colon). (medlineplus.gov)
- Long-segment disease occurs when nerve cells are missing from most of the large intestine and is the more severe type. (medlineplus.gov)
- Hirschsprung disease is a blockage of the large intestine. (adam.com)
- Babies with Hirschsprung disease are missing nerve cells in all or part of the large intestine. (tidelandshealth.org)
- In babies with Hirschsprung disease, the nerve cells don't grow past a certain part of the large intestine. (tidelandshealth.org)
- Hirschsprung disease is a congenital condition that affects the large intestine, resulting in a lack of nerve cells in certain segments of the bowel . (nurseslabs.com)
Intestinal obstruction1
- Congenital aganglionic megacolon , also called Hirschsprung disease , is characterized by persistent constipation resulting from partial or complete intestinal obstruction of mechanical origin. (nurseslabs.com)
Disorders5
- Motility disorders and Hirschsprung disease. (adam.com)
- We take a team-based approach to care for children with colorectal conditions such as Hirschsprung disease and other anorectal and pelvic floor disorders. (childrensmercy.org)
- A high prevalence of cutaneous disorders is expected, because most patients with ESRD have an underlying disease process with cutaneous manifestations. (medscape.com)
- Consequently, dermatologic manifestations of renal disease may be divided into 3 general categories including: (1) dermatologic manifestations of diseases associated with the development of ESRD, (2) dermatologic manifestations of uremia, and (3) dermatologic disorders associated with renal transplantation. (medscape.com)
- These systemic disorders and the associated renal diseases and cutaneous manifestations are tabulated in Table 1, below. (medscape.com)
Colon5
- Hirschsprung disease is a developmental disorder characterized by the absence of ganglia in the distal colon, resulting in a functional obstruction. (medscape.com)
- Hirschsprung disease is a congenital anomaly consisting of a failure of neuronal colonization (and thus a failure of innervation) of the lower intestine, usually limited to the colon, resulting in partial or total functional obstruction. (msdmanuals.com)
- The likelihood of disease among family members increases with increasing length of the involved gut-3 to 8% for disease of the distal colon and up to 20% for disease involving the entire colon. (msdmanuals.com)
- The disease is due to the absence of enteric ganglion cells in the distal colon that results in functional constipation. (jomi.com)
- Hirschsprung disease results from the absence of enteric neurons within the myenteric and submucosal plexus of the rectum and/or colon . (nurseslabs.com)
Symptoms3
- What are the symptoms of Hirschsprung disease in a child? (tidelandshealth.org)
- Most babies with Hirschsprung disease have symptoms in the first few weeks of life. (tidelandshealth.org)
- Symptoms of Hirschsprung disease may seem like other health problems. (tidelandshealth.org)
Constipation and abdominal1
- Despite significant constipation and abdominal distention, children with Hirschsprung disease rarely develop encopresis (fecal incontinence secondary to impacted stools). (medscape.com)
Bowel3
- In Hirschsprung disease, the nerves are missing from a part of the bowel. (adam.com)
- Treatment for this disease requires the resection of the abnormal bowel segment in order to restore the functions of the healthy part of the intestine. (scielo.sa.cr)
- Children with Hirschsprung disease aren't able to pass a bowel movement, or do so with difficulty. (akronchildrens.org)
Clinical3
- This results in clinical Hirschsprung disease. (nurseslabs.com)
- The purpose of this article is to integrate renal and cutaneous aspects of disease as well as highlight some important, although frequently underappreciated, clinical or laboratory findings that ally renal and skin diseases. (medscape.com)
- Birth defects were identified through International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 740.00-759.9. (medscape.com)
Severe4
- Without these nerves in parts of the intestine, the material cannot be pushed through, causing severe constipation or complete blockage of the intestine in people with Hirschsprung disease. (medlineplus.gov)
- Patients with less severe disease (short segment HD) may not be diagnosed until later in life. (jomi.com)
- Hirschsprung disease is typically diagnosed in infancy or early childhood, and prompt recognition and intervention are vital to prevent severe complications. (nurseslabs.com)
- In some cases, aganglionic megacolon or Hirschsprung disease may be severe enough to be recognized. (nurseslabs.com)
Anal1
- 9:00 The anal canal in Hirschsprung. (childrenscolorado.org)
Newborn period2
- Most cases of Hirschsprung disease are diagnosed in the newborn period. (medscape.com)
- During the newborn period, infants affected with Hirschsprung disease may present with failure of passage of meconium. (nurseslabs.com)
Disorder2
- Hirschsprung disease is an intestinal disorder characterized by the absence of nerves in parts of the intestine. (medlineplus.gov)
- A child is more at risk for Hirschsprung disease if there is a family history of the disorder. (tidelandshealth.org)
Patients9
- In patients with Hirschsprung disease, both myenteric and submucosal plexuses are absent. (medscape.com)
- RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients. (medscape.com)
- Approximately 10% of Hirschsprung patients have a family member who was also affected. (medscape.com)
- This predisposition is more common in patients with longer-segment disease. (medscape.com)
- Approximately 20 to 25% of patients with Hirschsprung disease have another congenital anomaly. (msdmanuals.com)
- Connect with other caregivers and patients with Hirschsprung disease type 3 and get the support you need. (rareguru.com)
- NIDDK translates and disseminates research findings to increase knowledge and understanding about health and disease among patients, health professionals, and the public. (nih.gov)
- Results of genetic-linkage analysis of patients with familial disease with both long-segment and short-segment phenotypes have shown close linkage with the RET locus. (uni-luebeck.de)
- Dermatologic manifestations of renal disease are not uncommon findings in patients with end-stage renal disease (ESRD). (medscape.com)
Children10
- Children who do not respond to constipation treatment for six months should also raise suspicion of such disease. (wikipedia.org)
- Older children with Hirschsprung disease usually have chronic constipation since birth. (medscape.com)
- The management and its epidemiology of this disease at the National Children´s Hospital during the period 2000 to 2010 were analyzed. (scielo.sa.cr)
- Which children are at risk for Hirschsprung disease? (tidelandshealth.org)
- Nearly all children with Hirschsprung disease are diagnosed during the first 2 years of life. (nurseslabs.com)
- a small number of children with Hirschsprung disease are not recognized until much later in childhood or adulthood. (nurseslabs.com)
- Older infants and children with Hirschsprung disease usually present with chronic constipation. (nurseslabs.com)
- Doctors aren't entirely sure why some children get Hirschsprung disease, but they do know it can run in families and affects boys more often than girls. (livelifelakshsize.com)
- For discussion of pheochromocytoma in children, see the Medscape Drugs & Diseases article Pediatric Pheochromocytoma . (medscape.com)
- and early intervention are mandatory to reduce morbidities and deaths due to this disease in children. (bvsalud.org)
Nerves1
- Absence of these nerves leads to the intestinal problems characteristic of Hirschsprung disease. (medlineplus.gov)
Occurs in approximately2
- Hirschsprung disease occurs in approximately 1 in 5,000 newborns. (medlineplus.gov)
- Hirschsprung disease occurs in approximately one in 5,000 newborns. (livelifelakshsize.com)
Diagnose1
- The disease is difficult to diagnose in adults, according to the case report. (livescience.com)
Genetic1
- The RareGuru disease database is regularly updated using data generously provided by GARD , the United States Genetic and Rare Disease Information Center. (rareguru.com)
Passage of meconium1
- Hirschsprung disease should be considered in any newborn with delayed passage of meconium or in any child with a history of chronic constipation since birth. (medscape.com)
Chronic2
- For patient education information, see Diabetes Center , Cholesterol Center , and Chronic Kidney Disease . (medscape.com)
- See also Chronic Kidney Disease and Chronic Renal Failure . (medscape.com)
Abdomen1
- In this article we will discuss the congenital gastrointestinal obstructions and also some acquired diseases that present as an acute abdomen in the neonate. (radiologyassistant.nl)
Affects1
- Long-segment disease is found in approximately 20 percent of people with Hirschsprung disease and affects men and women equally. (medlineplus.gov)
Short-segment2
- There are two main types of Hirschsprung disease, known as short-segment disease and long-segment disease, which are defined by the region of the intestine lacking nerve cells. (medlineplus.gov)
- For unknown reasons, short-segment disease is four times more common in men than in women. (medlineplus.gov)
Ostomy1
- A child who is very sick from Hirschsprung disease may first need ostomy surgery. (tidelandshealth.org)
Sporadic1
- The majority of Hirschsprung cases are sporadic. (medscape.com)
Typically1
- Typically, Hirschsprung disease is diagnosed shortly after birth, although it may develop well into adulthood, because of the presence of megacolon, or because the baby fails to pass the first stool (meconium) within 48 hours of delivery. (wikipedia.org)
HSCR2
- Background: Hirschsprung Disease (HSCR) is a congenital defect of the intestinal innervations characterized by complex inheritance. (unige.it)
- The observed maternal transmission bias for HSCR associated CNVs supports the hypothesis that in females these variants might be more tolerated, requiring additional alterations to develop HSCR disease. (unige.it)
Rarely1
- In particular, robotic surgery for rare congenital diseases, such as Hirschsprung disease, have been rarely addressed in recent years. (eurogen-ern.eu)
Centers1
- Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. (cdc.gov)
Meconium2
- Hirschsprung disease should be considered in any newborn who fails to pass meconium within 24-48 hours of birth. (medscape.com)
- Delay or failure to pass meconium is most often the first suggestion about the presence of this disease. (jomi.com)