Axenfeld-Rieger syndrome (ARS) is a rare congenital disease that is primarily characterized by ocular anterior segment anomalies but is also associated with craniofacial, dental, cardiac, and neurologic abnormalities. Over half of cases are linked with autosomal dominant mutations in either FOXC1 or PITX2, which reflects the molecular role of these genes in regulating neural crest cell contributions to the eye, face, and heart. Within the eye, ARS is classically defined as the combination of posterior embryotoxon with iris bridging strands (Axenfeld anomaly) and iris hypoplasia causing corectopia and pseudopolycoria (Rieger anomaly). Glaucoma due to iridogoniodysgenesis is the main source of morbidity and is typically diagnosed during infancy or childhood in over half of affected individuals. Angle bypass surgery, such as glaucoma drainage devices and trabeculectomies, is often needed to obtain intraocular pressure control. A multi-disciplinary approach including glaucoma specialists and pediatric ophthalmologists produces optimal outcomes as vision is dependent on many factors including glaucoma, refractive error, amblyopia and strabismus. Further, since ophthalmologists often make the diagnosis, it is important to refer patients with ARS to other specialists including dentistry, cardiology, and neurology.

UNASSIGNED: We describe the ocular findings in a patient with Alagille syndrome, included those obtained with ultra-widefield and anterior-segment optical coherence tomography (AS-OCT) imaging.
UNASSIGNED: A previously asymptomatic 29-year-old woman with a heterozygous pathogenic variant in the JAG1 gene was referred for an ophthalmic evaluation. The ocular abnormalities included bilateral posterior embryotoxon, iris atrophy, retinal pigmentary changes in the peripheral and peripapillary regions, and optic disc elevation. Ultra-widefield OCT showed bilateral retinal thinning with increased choroidal hyperreflectivity in the areas of peripheral retinopathy and optic disc elevation. AS-OCT confirmed bilateral iris atrophy.
UNASSIGNED: The ocular abnormalities observed in the present case represent clinical features characteristic of Alagille syndrome. Both ultra-widefield and AS-OCT were useful for assessing the ocular abnormalities in Alagille syndrome.

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant eye disorder that can also affect other organs of the human body. The condition is primarily characterized by the anterior segmental abnormalities of the eye. Here, we present an observational case series of a three-generation family with ARS and unexpected foveal anomaly.
METHODS: A 33-year-old woman was admitted to an Ophthalmology Clinic in Bialystok for left eye congenital cataract surgery. The patient (proband) was diagnosed with visual deterioration, multiple defects of iris, corectopia, displacement of the Schwalbe\'s line, and phenotypic characteristics of ARS. A perimetric examination indicated peripheral visual field loss and signs typical for glaucoma. Based on the phenotypic symptoms and genetic test, the patient was diagnosed with Axenfeld Rieger Syndrome. However, the optical coherence tomography of the macula showed foveal anomaly (absence of the physiological pit), which is not typically associated with this genetic disorder. The patient\'s family history revealed that her two daughters were undergoing treatment for congenital glaucoma, and one of the daughters also had foveal anomaly the same as her mother. Interestingly, an examination of the patient\'s mother showed typical phenotypic features of ARS such as a defect of the iris, posterior embryotoxon, and coloboma, as well as foveal anomaly. A genetic test confirmed PITX2 mutation in both, proband\'s two daughters and mother.
CONCLUSIONS: This study highlights the occurrence of ARS with unusual ophthalmic features such as foveal anomaly (absence of the physiological pit) in a three-generation family. Although ARS is known to represent the developmental defects of the anterior segment of the eye, it is very important to perform fundus evaluation to identify associated posterior segment anomalies that may affect visual acuity. The presence of ocular defects not typically associated with ARS suggests a wide spectrum of mutations within PITX2 gene which are required to identify in order to determine genotype- phenotype correlation in ARS affected individuals.

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Alagille syndrome (ALGS) is an autosomal dominant disorder, with multisystem involvement, which usually occurs due to Notch signaling pathway defects, mostly due to JAG1 mutation (ALGS type 1), but rarely due to neurogenic locus notch homolog protein (NOTCH2) mutation (ALGS type 2). It was suspected in cases having at least three out of five major clinical criteria: cholestasis with a paucity of the bile duct, congenital cardiac defects, ocular posterior embryotoxon, typical facial features, and skeletal malformation. Till date, no early predictive marker for hepatic outcome in ALGS has found. No genotypic or, phenotype features or correlation could predict the development of endstage liver disease, which poses a unique management challenge. Cases with progressive liver damage, unremitting cholestasis and intractable pruritus often depend on liver transplantation as last resort. The cardiac, and renal status should be well accessed before liver transplant for the better post-transplantation outcome. Most of the clinical manifestations usually improve the following transplant, except any change in stature. The post liver transplantation outcome was usually comparable with other conditions which require liver transplantation as a last resort, but in this disease the effect of long term immunosuppression on other affected systems not evaluated well till date. Therefore long term post transplant prospective study is required to address these issues. How to cite this article: Singh SP, Pati GK. Alagille Syndrome and the Liver: Current Insights. Euroasian J Hepatogastroenterol, 2018;8(2):140-147.

OBJECTIVE: Neonatal cholestasis can be associated with ocular findings that might aid in its diagnosis, e.g., Alagille syndrome (AGS) and Niemann Pick disease (NPD). We aimed to investigate the frequency of ocular manifestations in infants with cholestasis.
METHODS: This cross-sectional study included cholestatic infants presenting to the Paediatric Hepatology Unit, Cairo University Paediatric Hospital, Cairo, Egypt. All infants underwent examination of lid, ocular motility, anterior and posterior segments and measurement of intraocular pressure, cycloplegic refraction, ocular ultrasonography and vision.
RESULTS: The study included 112 infants with various cholestasis; 73 (65.2%) were males. The median age was 2months. Diagnosis was reached in 39 cases: 14 had AGS, 14 had biliary atresia (BA), 4 had NPD, 4 had post-haemolytic cholestasis, 2 had cytomegalovirus neonatal hepatitis, and one case had hepatorenal tyrosinaemia. Thirteen cases were probably having progressive familiar intrahepatic cholestasis (PFIC) type 1 or 2 considering their persistent cholestasis in the presence of normal gamma-glutamyl transpeptidase; 28 were left with a diagnosis of \"idiopathic neonatal hepatitis\" (INH), and 32 (28.6%) had no definite diagnosis. Ophthalmologic abnormalities were found in 39 cases (34.8%). The commonest finding was unilateral/bilateral optic nerve drusen in 12 (10.7%), followed by posterior embryotoxon in 11 (9.8%). Ocular findings were observed in 64.3% patients with AGS, 50% patients with NPD, 30.8% cases with suspected PFIC type 1or 2, 28.6% infants with INH, and 14.3% patients with BA.
CONCLUSIONS: Ophthalmologic findings are not uncommon among cholestatic infants. Ophthalmologic examination should be routinely performed, including assessment of anterior segment, fundus examination, and ocular ultrasound.

BACKGROUND: Alagille syndrome, a rare genetic disorder with autosomal dominant transmission, manifests with five major features: paucity of interlobular bile ducts, characteristic facies, posterior embryotoxon, vertebral defects, and peripheral pulmonary stenosis. Globally, only 500 cases have so far been reported, with only five cases reported in the Indian subcontinent. Rarely, Alagille syndrome also presents with skin manifestations and early-onset chronic liver disease, which was found in our case. We believe that we report what could be the first case of Alagille syndrome presenting with café au lait spots, as no such published case report could be found in the literature.
METHODS: We report an unusual case of childhood cholestatic jaundice with neonatal onset of jaundice. A 10-year-old boy from the Indian subcontinent presented with obstructive jaundice from early infancy. He also had recurrent fractures of his upper limb bones, intermittent bleeding from his nose, productive cough, decreased night vision, hyperpigmented spots over his skin, and progressive enlargement of his abdomen. Histological examination of a liver biopsy specimen revealed a paucity of bile ducts and changes suggestive of chronic liver disease. Our patient was diagnosed with Alagille syndrome and managed conservatively but died 1 year after the final diagnosis.
CONCLUSIONS: This particular syndromic form of paucity of bile duct disorder has been rarely reported in the Indian literature so far. Our case is notable because the child had café au lait spots and very early onset of chronic liver disease, which is quite rare in Alagille syndrome. We believe this to be the first case report on Alagille syndrome manifesting with café au lait syndrome and such early onset of chronic liver disease.

OBJECTIVE: To determine the prevalence of posterior embryotoxon, corneal opacity, pigment on endothelium, corneal dystrophy, and corneal vascularization in a middle-aged Iranian population, and their association with age and sex.
METHODS: In a cross-sectional study with multistage cluster sampling, subjects were chosen from 40 to 64-year-old residents of Shahroud in northern Iran. Participants had ophthalmic examinations before and after pupil dilation. Corneal abnormalities were diagnosed by an ophthalmologist using a slit lamp.
RESULTS: Of the 6311 invitees, 5190 people (82.2%) participated; 58.6% (n=3040) were female. The prevalence of posterior embryotoxon, corneal opacity, and pigment on endothelium were 14.7% (95% CI: 13.4-16.0), 4.1% (95% CI: 3.4-4.7) and 1.2% (95% CI: 0.9-1.5), respectively, and corneal dystrophy and corneal vascularization were seen in 0.3% (95% CI: 0.2-0.5) and 3.7% (95% CI: 3.0-4.3), respectively. Unlike posterior embryotoxon, the prevalence of all studied abnormalities increased with age after adjusting for sex. The prevalence of posterior embryotoxon (p=0.023) and corneal dystrophy (p=0.038) was significantly higher in women, and the prevalence of corneal opacity (p<0.001) was significantly higher in men. After adjusting for age, sex, and cataract, cases with corneal opacity and corneal vascularization demonstrated significantly worse uncorrected and corrected visual acuity (p<0.001).
CONCLUSIONS: This report is the first to explore the prevalence of a variety of corneal conditions in a Middle-Eastern population. The findings indicate that one out of five people may have some sort of corneal conditions, and some can impact corrected visual acuity.