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Journal of Multidisciplinary Healthcare 2022Alagille syndrome (ALGS) is an autosomal dominant disorder characterized by involvement of various organ systems. It predominantly affects the liver, skeleton, heart,... (Review)
Review
Alagille syndrome (ALGS) is an autosomal dominant disorder characterized by involvement of various organ systems. It predominantly affects the liver, skeleton, heart, kidneys, eyes and major blood vessels. With myriads of presentations across different age groups, ALGS is usually suspected in infants presenting with high gamma glutamyl transpeptidase cholestasis and/or congenital heart disease. In children it may present with decompensated cirrhosis, intellectual disability or short stature, and in adults vascular events like stroke or ruptured berry aneurysm are more commonly noted. Liver transplantation (LT) is indicated in children with cholestasis progressing to cirrhosis with decompensation. Other indications for LT include intractable pruritus, recurrent fractures, hepatocellular carcinoma and disfiguring xanthomas. Due to an increased risk of renal impairment noted in ALGS, these patients would require optimized renal sparing immunosuppression in the post-transplant period. As the systemic manifestations of ALGS are protean and a wider spectrum is being increasingly elucidated, a multidisciplinary team needs to be involved in managing these patients. Moreover, many basic-science and clinical questions especially with regard to its presentation and management remain unanswered. The aim of this review is to provide updated insights into the management of the multi-system involvement of ALGS.
PubMed: 35237041
DOI: 10.2147/JMDH.S295441 -
Obstetric Medicine Mar 2021Alagille syndrome is an autosomal dominant multisystem disorder with an estimated frequency of 1 in 30 000. Only a small number of pregnancy outcomes have been described...
Alagille syndrome is an autosomal dominant multisystem disorder with an estimated frequency of 1 in 30 000. Only a small number of pregnancy outcomes have been described in women with this condition. The report details the pregnancy outcomes of two women with Alagille syndrome. We also review the literature pertaining to this syndrome in pregnancy and demonstrate a significant risk of adverse pregnancy outcomes.
PubMed: 33995572
DOI: 10.1177/1753495X19849738 -
Neonatal Network : NN Nov 2017Alagille syndrome (AGS) is a highly complex, multisystem, autosomal dominant disorder that is caused by a defect in the Notch signaling pathway. This syndrome mainly... (Review)
Review
Alagille syndrome (AGS) is a highly complex, multisystem, autosomal dominant disorder that is caused by a defect in the Notch signaling pathway. This syndrome mainly affects the liver, causing significant cholestasis, which is caused by a paucity of intrahepatic bile ducts. There can be cardiac involvement, including, but not limited to, pulmonary stenosis and tetralogy of Fallot. Patients can also present with butterfly vertebra, ocular issues, and vascular events. Because this syndrome follows an autosomal dominant inheritance, it can have variable expression even in the same family line. For infants in the NICU who have a cardiac defect and persistent hyperbilirubinemia after two weeks of age, genetic testing for AGS should be considered. Early detection and diagnosis can lead to improved outcomes. In this discussion of AGS, the clinical features as well as management are discussed.
Topics: Alagille Syndrome; Disease Management; Humans; Infant; Jagged-1 Protein; Neonatal Nursing; Receptors, Notch; Signal Transduction
PubMed: 29185945
DOI: 10.1891/0730-0832.36.6.343 -
Frontiers in Pharmacology 2021Advancements in treatment for the rare genetic disorder known as Alagille Syndrome (ALGS) have been regrettably slow. The large variety of mutations to the JAG1 and... (Review)
Review
Advancements in treatment for the rare genetic disorder known as Alagille Syndrome (ALGS) have been regrettably slow. The large variety of mutations to the JAG1 and NOTCH2 genes which lead to ALGS pose a unique challenge for developing targeted treatments. Due to the central role of the Notch signaling pathway in several cancers, traditional treatment modalities which compensate for the loss in activity caused by mutation are rightly excluded. Unfortunately, current treatment plans for ALGS focus on relieving symptoms of the disorder and do not address the underlying causes of disease. Here we review several of the current and potential key technologies and strategies which may yield a significant leap in developing targeted therapies for this disorder.
PubMed: 34497511
DOI: 10.3389/fphar.2021.704586 -
The Application of Clinical Genetics 2016Alagille syndrome is an autosomal dominant, complex multisystem disorder characterized by the presence of three out of five major clinical criteria: cholestasis with... (Review)
Review
Alagille syndrome is an autosomal dominant, complex multisystem disorder characterized by the presence of three out of five major clinical criteria: cholestasis with bile duct paucity on liver biopsy, congenital cardiac defects (with particular involvement of the pulmonary arteries), posterior embryotoxon in the eye, characteristic facial features, and butterfly vertebrae. Renal and vascular abnormalities can also occur. Inter- and intrafamilial variabilities in the clinical manifestations are common. We reviewed the clinical features and management as well as the molecular basis of Alagille syndrome.
PubMed: 27418850
DOI: 10.2147/TACG.S86420 -
World Journal of Gastroenterology Mar 2024Several diseases originate from bile duct pathology. Despite studies on these diseases, certain etiologies of some of them still cannot be concluded. The most common... (Review)
Review
Several diseases originate from bile duct pathology. Despite studies on these diseases, certain etiologies of some of them still cannot be concluded. The most common disease of the bile duct in newborns is biliary atresia, whose prognosis varies according to the age of surgical correction. Other diseases such as Alagille syndrome, inspissated bile duct syndrome, and choledochal cysts are also time-sensitive because they can cause severe liver damage due to obstruction. The majority of these diseases present with cholestatic jaundice in the newborn or infant period, which is quite difficult to differentiate regarding clinical acumen and initial investigations. Intraoperative cholangiography is potentially necessary to make an accurate diagnosis, and further treatment will be performed synchronously or planned as findings suggest. This article provides a concise review of bile duct diseases, with interesting cases.
Topics: Infant; Child; Infant, Newborn; Humans; Bile Ducts; Biliary Atresia; Choledochal Cyst; Bile Duct Diseases; Cholangiography
PubMed: 38577180
DOI: 10.3748/wjg.v30.i9.1043 -
Indian Journal of Otolaryngology and... Dec 2022Alagille Syndrome (ALGS) is a rare, autosomal dominant inherited disorder that causes abnormalities of liver, eye, heart, skeleton and distinctive facial appearance....
Alagille Syndrome (ALGS) is a rare, autosomal dominant inherited disorder that causes abnormalities of liver, eye, heart, skeleton and distinctive facial appearance. ALGS is caused by mutation in one of two genes: JAG1 and NOTCH2. There are some reports of Hearing Loss in patients with ALGS raising the possibility of involvement of both structural components of middle ear and sensorineural components of the inner ear. The present case study was to emphasize audiological perspectives of Alagille Syndrome in a nine year old female child. Audiologists must be well aware of the typical features and clinical perspectives of ALGS and should be an expert in selecting appropriate tests and in interpreting findings.
PubMed: 36742831
DOI: 10.1007/s12070-020-02293-y -
Advances in Experimental Medicine and... 2021Interactions between liver cells are closely regulated by Notch signaling. Notch signaling has been reported clinically related to bile duct hypogenesis in Alagille... (Review)
Review
Interactions between liver cells are closely regulated by Notch signaling. Notch signaling has been reported clinically related to bile duct hypogenesis in Alagille syndrome, which is caused by mutations in the Jagged1 gene. Notch activation and hepatocarcinogenesis are closely associated since cancer signaling is affected by the development of liver cells and cancer stem cells. Gene expression and genomic analysis using a microarray revealed that abnormalities in Notch-related genes were associated with the aggressiveness of liver cancer. This pattern was also accompanied with α-fetoprotein- and EpCAM-expressing phenotypes in vitro, in vivo, and in clinical tissues. Hepatitis B or C virus chronic infection or alcohol- or steatosis-related liver fibrosis induces liver cancer. Previous reports demonstrated that HBx, a hepatitis B virus protein, was associated with Jagged1 expression. We found that the Jagged1 and Notch1 signaling pathways were closely associated with the transcription of covalently closed circular hepatitis B virus DNA, which regulated cAMP response element-binding protein, thereby affecting Notch1 regulation by the E3 ubiquitin ligase ITCH. This viral pathogenesis in hepatocytes induces liver cancer. In conclusion, Notch signaling exerts various actions and is a clinical signature associated with hepatocarcinogenesis and liver context-related developmental function.
Topics: Hepatitis; Hepatitis B virus; Humans; Liver Neoplasms; Receptors, Notch; Repressor Proteins; Signal Transduction; Ubiquitin-Protein Ligases
PubMed: 33034027
DOI: 10.1007/978-3-030-55031-8_6 -
World Journal of Gastroenterology Jul 2014Cholestatic liver disease consists of a variety of disorders. Primary sclerosing cholangitis and primary biliary cirrhosis are the most commonly recognized cholestatic... (Review)
Review
Cholestatic liver disease consists of a variety of disorders. Primary sclerosing cholangitis and primary biliary cirrhosis are the most commonly recognized cholestatic liver disease in the adult population, while biliary atresia and Alagille syndrome are commonly recognized in the pediatric population. In infants, the causes are usually congenital or inherited. Even though jaundice is a hallmark of cholestasis, it is not always seen in adult patients with chronic liver disease. Patients can have "silent" progressive cholestatic liver disease for years prior to development of symptoms such as jaundice and pruritus. In this review, we will discuss some of the atypical causes of cholestatic liver disease such as benign recurrent intrahepatic cholestasis, progressive familial intrahepatic cholestasis, Alagille Syndrome, biliary atresia, total parenteral nutrition induced cholestasis and cholestasis secondary to drug induced liver injury.
Topics: Alagille Syndrome; Biliary Atresia; Chemical and Drug Induced Liver Injury; Cholestasis; Cholestasis, Intrahepatic; Female; Genetic Predisposition to Disease; Heredity; Humans; Male; Parenteral Nutrition, Total; Pedigree; Phenotype; Pregnancy; Pregnancy Complications; Prognosis; Recurrence; Risk Factors; Sepsis
PubMed: 25071336
DOI: 10.3748/wjg.v20.i28.9418 -
Expert Review of Gastroenterology &... 2023Alagille syndrome (ALGS) is an autosomal dominant, multisystem genetic disorder with wide phenotypic variability caused by mutations in the Notch signaling pathway,... (Review)
Review
INTRODUCTION
Alagille syndrome (ALGS) is an autosomal dominant, multisystem genetic disorder with wide phenotypic variability caused by mutations in the Notch signaling pathway, specifically from mutations in either the Jagged1 (JAG1) or NOTCH2 gene. The range of clinical features in ALGS can involve various organ systems including the liver, heart, eyes, skeleton, kidney, and vasculature. Despite the genetic mutations being well-defined, there is variable expressivity and individuals with the same mutation may have different clinical phenotypes.
AREAS COVERED
While no clear genotype-phenotype correlation has been identified in ALGS, this review will summarize what is currently known about the genotype-phenotype relationship and how this relationship influences the treatment of the multisystemic disorder. This review includes discussion of numerous studies which have focused on describing the genotype-phenotype relationship of different organ systems in ALGS as well as relevant basic science and population studies of ALGS. A thorough literature search was completed via the PubMed and National Library of Medicine GeneReviews databases including dates from 1969, when ALGS was first identified, to February 2023.
EXPERT OPINION
The genetics of ALGS are well defined; however, ongoing investigation to identify genotype-phenotype relationships as well as genetic modifiers as potential therapeutic targets is needed. Clinicians and patients alike would benefit from identification of a correlation to aid in diagnostic evaluation and management.
Topics: Humans; Alagille Syndrome; Mutation; Phenotype; Genotype
PubMed: 37668532
DOI: 10.1080/17474124.2023.2255518