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World Journal of Gastroenterology Mar 2014Irritable bowel syndrome (IBS) is a common condition characterized by abdominal pain or discomfort, bloating, and altered stool form and passage. Small intestinal... (Review)
Review
Irritable bowel syndrome (IBS) is a common condition characterized by abdominal pain or discomfort, bloating, and altered stool form and passage. Small intestinal bacterial overgrowth (SIBO) is a condition in which there is overgrowth of bacteria in small bowel in excess of 10⁵ colony forming units per milliliter on culture of the upper gut aspirate. Frequency of SIBO varied from 4%-78% among patients with IBS and from 1%-40% among controls. Higher frequency in some studies might be due to fallacious criteria [post-lactulose breath-hydrogen rise 20 PPM above basal within 90 min (early-peak)]. Glucose hydrogen breath test (GHBT) has a low sensitivity to diagnose SIBO. Hence, studies based on GHBT might have under-estimated frequency of SIBO. Therefore, it is important to analyze these studies carefully to evaluate whether the reported association between IBS and SIBO is over or under-projected. This review evaluates studies on association between SIBO and IBS, discordance between different studies, their strength and weakness including methodological issues and evidence on therapeutic manipulation of gut flora on symptoms of IBS.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Breath Tests; Fermentation; Host-Parasite Interactions; Humans; Intestine, Small; Irritable Bowel Syndrome; Phenotype; Predictive Value of Tests; Probiotics; Risk Factors; Treatment Outcome
PubMed: 24627585
DOI: 10.3748/wjg.v20.i10.2482 -
Frontiers in Medicine 2023
PubMed: 37064030
DOI: 10.3389/fmed.2023.1188047 -
American Journal of Medical Genetics.... Dec 2019Increased risk of thromboembolism has been recognized in individuals with mosaic overgrowth disorders, Proteus syndrome (PS) and PIK3CA-related overgrowth spectrum...
Increased risk of thromboembolism has been recognized in individuals with mosaic overgrowth disorders, Proteus syndrome (PS) and PIK3CA-related overgrowth spectrum (PROS), including Klippel-Trenaunay syndrome and CLOVES syndrome. PS and PROS have distinct, yet overlapping clinical findings and are caused by somatic pathogenic variants in the PI3K/AKT gene signaling pathway. PS is caused by a single somatic activating AKT1 c.49G > A p.E17K variant while PROS can be caused one of multiple variants in PIK3CA. The role of prothrombotic factors, endothelial cell adhesion molecules, and vascular malformations in both PS and PROS have not been previously investigated. A pilot study of prospective clinical and laboratory evaluations with the purposes of identifying potential risk factors for thrombosis was conducted. Doppler ultrasounds and magnetic resonance angiogram/ venography (MRA/MRV) scans identified vascular malformations in PS and PROS that were not appreciated on physical examination. Abnormal D-dimers (0.60-2.0 mcg/ml) occurred in half of individuals, many having vascular malformations, but no thromboses. Soluble vascular endothelial markers, including thrombomodulin, soluble vascular adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), E-selectin, and P-selectin were significantly higher in PS and PROS compared to controls. However, no single attribute was identified that explained the risk of thrombosis. Predisposition to thrombosis is likely multifactorial with risk factors including chronic stasis within vascular malformations, stasis from impaired mobility (e.g., following surgery), decreased anticoagulant proteins, and effects of AKT1 and PIK3CA variants on vascular endothelium. Based on our findings, we propose clinical recommendations for surveillance of thrombosis in PS and PROS.
Topics: Adolescent; Adult; Child; Child, Preschool; Class I Phosphatidylinositol 3-Kinases; Female; Genetic Predisposition to Disease; Growth Disorders; Humans; Infant; Male; Middle Aged; Pilot Projects; Prospective Studies; Proteus Syndrome; Thrombosis; Young Adult
PubMed: 31490637
DOI: 10.1002/ajmg.c.31735 -
BioRxiv : the Preprint Server For... Jun 2023Weaver syndrome is a Mendelian disorder of the epigenetic machinery (MDEM) caused by germline pathogenic variants in , which encodes the predominant H3K27...
Weaver syndrome is a Mendelian disorder of the epigenetic machinery (MDEM) caused by germline pathogenic variants in , which encodes the predominant H3K27 methyltransferase and key enzymatic component of Polycomb repressive complex 2 (PRC2). Weaver syndrome is characterized by striking overgrowth and advanced bone age, intellectual disability, and distinctive facies. We generated a mouse model for the most common Weaver syndrome missense variant, p.R684C. mouse embryonic fibroblasts (MEFs) showed global depletion of H3K27me3. mice had abnormal bone parameters indicative of skeletal overgrowth, and osteoblasts showed increased osteogenic activity. RNA-seq comparing osteoblasts differentiated from and bone marrow mesenchymal stem cells (BM-MSCs) indicated collective dysregulation of the BMP pathway and osteoblast differentiation. Inhibition of the opposing H3K27 demethylases Kdm6a/6b substantially reversed the excessive osteogenesis in cells both at the transcriptional and phenotypic levels. This supports both the ideas that writers and erasers of histone marks exist in a fine balance to maintain epigenome state, and that epigenetic modulating agents have therapeutic potential for the treatment of MDEMs.
PubMed: 37425751
DOI: 10.1101/2023.06.23.546270 -
World Journal of Gastroenterology Jun 2014Breath tests are non-invasive tests and can detect H₂ and CH₄ gases which are produced by bacterial fermentation of unabsorbed intestinal carbohydrate and are... (Review)
Review
Breath tests are non-invasive tests and can detect H₂ and CH₄ gases which are produced by bacterial fermentation of unabsorbed intestinal carbohydrate and are excreted in the breath. These tests are used in the diagnosis of carbohydrate malabsorption, small intestinal bacterial overgrowth, and for measuring the orocecal transit time. Malabsorption of carbohydrates is a key trigger of irritable bowel syndrome (IBS)-type symptoms such as diarrhea and/or constipation, bloating, excess flatulence, headaches and lack of energy. Abdominal bloating is a common nonspecific symptom which can negatively impact quality of life. It may reflect dietary imbalance, such as excess fiber intake, or may be a manifestation of IBS. However, bloating may also represent small intestinal bacterial overgrowth. Patients with persistent symptoms of abdominal bloating and distension despite dietary interventions should be referred for H₂ breath testing to determine the presence or absence of bacterial overgrowth. If bacterial overgrowth is identified, patients are typically treated with antibiotics. Evaluation of IBS generally includes testing of other disorders that cause similar symptoms. Carbohydrate malabsorption (lactose, fructose, sorbitol) can cause abdominal fullness, bloating, nausea, abdominal pain, flatulence, and diarrhea, which are similar to the symptoms of IBS. However, it is unclear if these digestive disorders contribute to or cause the symptoms of IBS. Research studies show that a proper diagnosis and effective dietary intervention significantly reduces the severity and frequency of gastrointestinal symptoms in IBS. Thus, diagnosis of malabsorption of these carbohydrates in IBS using a breath test is very important to guide the clinician in the proper treatment of IBS patients.
Topics: Bacteria; Biomarkers; Breath Tests; Dietary Carbohydrates; Fermentation; Gases; Humans; Intestines; Irritable Bowel Syndrome; Lactose Intolerance; Predictive Value of Tests; Prognosis
PubMed: 24976698
DOI: 10.3748/wjg.v20.i24.7587 -
Clinical and Experimental Pediatrics Sep 2023Small intestinal bacterial overgrowth (SIBO) is defined as the presence of an excessive number of bacteria within the small bowel. Pediatric SIBO is a heterogeneous...
Small intestinal bacterial overgrowth (SIBO) is defined as the presence of an excessive number of bacteria within the small bowel. Pediatric SIBO is a heterogeneous disorder that manifests as various symptoms ranging from mild gastrointestinal symptoms to malabsorption or malnutrition. The carbohydrate breath test is a commonly used, safe, and noninvasive diagnostic test; however, a standardized methodology is lacking. Multiple factors, such as neuromuscular disorders, systemic diseases, chronic drug use, or altered intestinal anatomy that disturb intestinal motility or induce an abnormality in the body's defense systems against intestinal bacteria, predispose children to SIBO. The high prevalence and similar symptoms of SIBO in functional gastrointestinal disorders, including irritable bowel syndrome, suggest an association between them. The principles of treatment include managing predisposing conditions, nutritional support, symptom control, and antibacterial treatment. Rifaximin is the most commonly used drug. To date, studies of antibiotic treatment in pediatric populations with irritable bowel syndrome or SIBO are lacking and have shown mixed results. Here we review the prevalence, diagnostic tests, and treatment results in pediatric populations.
PubMed: 37599259
DOI: 10.3345/cep.2022.00969 -
Ugeskrift For Laeger Jun 2021We report a boy with congenital hemihyperplasia, umbilical hernia and temporary neonatal hypoglycemia, who was confirmed to have BWS caused by paternal uniparental...
We report a boy with congenital hemihyperplasia, umbilical hernia and temporary neonatal hypoglycemia, who was confirmed to have BWS caused by paternal uniparental disomy of chromosome 11p15.5. Additional phenotypic features comprising scoliosis, nephromegaly, focal partial epilepsy and delayed psychomotor development were coherent with the underlying genotype. This case emphasizes the importance of identifying the underlying genetic variant in order to acknowledge and manage the associated clinical complications and specific risk profile.
Topics: Beckwith-Wiedemann Syndrome; Hernia, Umbilical; Humans; Hyperplasia; Infant, Newborn; Kidney Diseases; Male; Uniparental Disomy
PubMed: 34120690
DOI: No ID Found -
Deutsches Arzteblatt International Feb 2020Genetic mosaics arise through new mutations occurring after fertiliza- tion (i.e., postzygotic mutations). Mosaics have been described in recent years as the cause of... (Review)
Review
BACKGROUND
Genetic mosaics arise through new mutations occurring after fertiliza- tion (i.e., postzygotic mutations). Mosaics have been described in recent years as the cause of many different disorders; many of these are neurocutaneous diseases and syndromal developmental disorders, each with a characteristic phenotype. In some of these disorders, there is a genetic predisposition to the development of tumors. This article is intended as an overview of selected mosaic diseases.
METHODS
This review is based on publications retrieved by a selective search in PubMed, with particular attention to recent articles in high-ranking journals dealing with asymmetric growth disturbances, focal brain malformations, mosaic diseases due to dysregulation of the RAS/RAF signaling pathway (mosaic RASopathies), and vascular malformations.
RESULTS
The identification of postzygotic mutations has led to the reclassification of traditional disease entities and to a better understanding of their pathogenesis. Diagnosis is aided by modern next-generation sequencing (NGS) techniques that allow the detection even of low-grade mosaics. Many mosaic mutations are not detectable in blood, but only in the affected tissue, e.g., the skin. Genetic mosaic diseases often manifest themselves in the skin and brain, and by facial dysmorphism, asymmetrical growth disturbances, and vascular malformations.
CONCLUSION
The possibility of a mosaic disease should be kept in mind in the diag- nostic evaluation of patients with asymmetrical growth disturbances, focal neuronal migration disturbances, vascular malformations, and linear skin abnormalities. The demonstration of a postzygotic mutation often affords relief to the parents of an affected child, since this means that there is no increased risk for recurrence of the same disorder in future children. Correct classification is important, as molecular available for certain mosaic diseases, e.g., PIK3CA-related overgrowth spectrum (PROS) disorder.
Topics: Humans; Mosaicism; Vascular Malformations
PubMed: 32181732
DOI: 10.3238/arztebl.2020.0119 -
Frontiers in Pediatrics 2023Sotos Syndrome (SS, OMIM#117550) is a heterogeneous genetic condition, recognized by three main clinical features present in most cases: overgrowth with macrocephaly,...
INTRODUCTION
Sotos Syndrome (SS, OMIM#117550) is a heterogeneous genetic condition, recognized by three main clinical features present in most cases: overgrowth with macrocephaly, typical facial appearance and different degrees of intellectual disability. Three different types are described caused by variants or deletions/duplications in and genes. We aimed to describe a cohort of pediatric patients reporting the typical and unexpected findings in order to expand the phenotype of this syndrome and trying to find genotype-phenotype correlations.
METHODS
In our referral center, we collected and analyzed clinical and genetic data of 31-patients cohort diagnosed with SS.
RESULTS
All of them presented with overgrowth, typical dysmorphic features and different degree of developmental delay. Although structural cardiac defects have been reported in SS, non-structural diseases such as pericarditis were outstanding in our cohort. Moreover, we described here novel oncological malignancies not previously linked to SS such as splenic hamartoma, retinal melanocytoma and acute lymphocytic leukemia. Finally, five patients suffered from recurrent onychocryptosis that required surgical procedures, as an unreported prevalent medical condition.
DISCUSSION
This is the first study focusing on multiple atypical symptoms in SS at the time that revisits the spectrum of clinical and molecular basis of this heterogeneous entity trying to unravel a genotype-phenotype correlation.
PubMed: 37384309
DOI: 10.3389/fped.2023.1184529 -
BMC Medical Genomics Sep 2022The genetic features and treatment strategies of lateralized overgrowth have been elusive. We performed this study to analyze the genetic characteristics and treatment...
BACKGROUND
The genetic features and treatment strategies of lateralized overgrowth have been elusive. We performed this study to analyze the genetic characteristics and treatment results of propranolol- or alpelisib-treated patients with lateralized overgrowth.
METHODS
Fifteen patients with lateralized overgrowth were involved. Clinical characteristics and whole-body magnetic resonance imaging (WB-MRI) findings were evaluated. Targeted exome sequencing with a gene panel of affected tissue and peripheral white blood cells was performed. Propranolol was administered and treatment results were evaluated. The PIK3CA inhibitor alpelisib was prescribed via a managed access program.
RESULTS
The identified mutations were PIK3CA (n = 7), KRAS (n = 2), PTEN (n = 1), MAP2K3 (n = 1), GNAQ (n = 1), TBC1D4 (n = 1), and TEK (n = 1). Propranolol was prescribed in 12 patients, and 7 experienced mild improvement of symptoms. Alpelisib was prescribed in two patients with a PIK3CA mutation, and the reduction of proliferated masses after 1 year of treatment was proved by WB-MRI.
CONCLUSIONS
Targeted exome sequencing identified various genetic features of lateralized overgrowth. Propranolol could be applied as an adjuvant therapy for reducing vascular symptoms, but a PIK3CA inhibitor would be the primary therapeutic strategy for PIK3CA-related overgrowth syndrome.
Topics: Class I Phosphatidylinositol 3-Kinases; Humans; Magnetic Resonance Imaging; Mutation; Propranolol; Proto-Oncogene Proteins p21(ras); Thiazoles; Whole Body Imaging
PubMed: 36175890
DOI: 10.1186/s12920-022-01362-1