Williams syndrome presenting with findings consistent with Alagille syndrome.
Ontology highlight
ABSTRACT:
SUBMITTER: Sakhuja P
PROVIDER: S-EPMC4317206 | biostudies-literature | 2015 Jan
REPOSITORIES: biostudies-literature
Publications
Williams syndrome presenting with findings consistent with Alagille syndrome.
Sakhuja Pankaj P Whyte Hilary H Kamath Binita B Martin Nicole N Chitayat David D
Clinical case reports 20141107 1
Conjugated hyperbilirubinemia, posterior embryotoxon, and vertebral anomalies are not features of William syndrome (WS). We herein report a preterm infant who presented with features suggestive of Alagille syndrome, but microarray showed findings consistent with WS. This further extends the phenotype of WS and emphasizes the need for microarray analysis. ...[more]
Similar Datasets
Project description:Alagille syndrome (ALGS) is a multisystemic disease caused by mutations in genes of Notch pathway, which regulates embryonic cell differentiation and angiogenesis. Clinically, ALGS is characterized by cholestasis, cardiac defects, characteristic facial features, skeletal and ophthalmologic abnormalities. The aim of this review is to illustrate neuroradiological findings in ALGS, which are less well-known and prevalent, including cerebrovascular anomalies (such as aneurysms, dolichoectasia, Moyamoya syndrome and venous peculiarities), Chiari 1 malformation, craniosynostosis, intracranial hypertension, and vertebral anomalies (namely butterfly vertebra, hemivertebra, and craniocervical junction anomalies). Rarer cerebral midline malformations and temporal bone anomalies have also been described.
| S-EPMC8722249 | biostudies-literature
Project description:Previous examination in a small number of individuals with Williams syndrome (also referred to as Williams-Beuren syndrome) has shown subtly softer skin and reduced deposition of elastin, an elastic matrix protein important in tissue recoil. No quantitative information about skin elasticity in individuals with Williams syndrome is available; nor has there been a complete report of dermatologic findings in this population. To fill this knowledge gap, 94 patients with Williams syndrome aged 7-50 years were recruited as part of the skin and vascular elasticity (WS-SAVE) study. They underwent either a clinical dermatologic assessment by trained dermatologists (2010 WSA family meeting) or measurement of biomechanical properties of the skin with the DermaLab™ suction cup (2012 WSA family meeting). Clinical assessment confirmed that soft skin is common in this population (83%), as is premature graying of the hair (80% of those 20 years or older), while wrinkles (92%), and abnormal scarring (33%) were detected in larger than expected proportions. Biomechanical studies detected statistically significant differences in dP (the pressure required to lift the skin), dT (the time required to raise the skin through a prescribed gradient), VE (viscoelasticity), and E (Young's modulus) relative to matched controls. The RT (retraction time) also trended longer but was not significant. The biomechanical differences noted in these patients did not correlate with the presence of vascular defects also attributable to elastin insufficiency (vascular stiffness, hypertension, and arterial stenosis) suggesting the presence of tissue specific modifiers that modulate the impact of elastin insufficiency in each tissue.
| S-EPMC4134746 | biostudies-literature
Project description:Williams-Beuren syndrome (WBS; OMIM #194050) is a developmental disorder characterized by congenital heart disease, intellectual disability, dysmorphic facial features and ophthalmologic abnormalities. Oral abnormalities are also described in clinical manifestations of the disease. This paper describes orofacial features in patients with WBS.Seventeen patients with a confirmed molecular diagnosis of WBS were examined for oral abnormalities through clinical oral evaluations and panoramic radiography.Malocclusion, specifically with dental midline deviation, and high-arched palate were the most common findings.The present results contribute to knowledge on the orofacial manifestations of WBS. Since such patients with WBS may develop severe oral abnormalities, early detection and treatment can help improve their quality of life.
| S-EPMC5822531 | biostudies-literature
Project description:Alagille syndrome (AGS) is a complex multisystem disorder that involves mainly the liver, heart, eyes, face, and skeleton. The main associated clinical features are chronic cholestasis due to a paucity of intrahepatic bile ducts, congenital heart disease primarily affecting pulmonary arteries, vertebral abnormalities, ocular embryotoxon, and peculiar facies. The manifestations generally become evident at a pediatric age. AGS is caused by defects in the Notch signaling pathway due to mutations in JAG1 or NOTCH2. It is inherited in an autosomal dominant pattern with a high degree of penetrance, but variable expressivity results in a wide range of clinical features. Here we report on a 31-year-old male patient who presented with elevated serum alkaline phosphatase and gamma-glutamyl transpeptidase, and was diagnosed with AGS associated with the JAG1 mutation after a comprehensive workup.
| S-EPMC5628001 | biostudies-literature
Project description:Alagille syndrome (OMIM 118450) is an autosomal dominant disorder associated with abnormalities of the liver, heart, eye, skeleton, and a characteristic facial appearance. Also referred to as the Alagille-Watson syndrome, syndromic bile duct paucity, and arteriohepatic dysplasia, it is a significant cause of neonatal jaundice and cholestasis in older children. In the fully expressed syndrome, affected subjects have intrahepatic bile duct paucity and cholestasis, in conjunction with cardiac malformations (most frequently peripheral pulmonary stenosis), ophthalmological abnormalities (typically of the anterior chamber with posterior embryotoxon being the most common), skeletal anomalies (most commonly butterfly vertebrae), and characteristic facial appearance. Inheritance is autosomal dominant, but expressivity is highly variable. Sibs and parents of probands are often found to have mild expression of the presumptive disease gene, with abnormalities of only one or two systems. The frequency of new mutations appears relatively high, estimated at between 15 and 50%. The disease gene has been mapped to chromosome 20 band p12 based on multiple patients described with cytogenetic or molecular rearrangements of this region. However, the frequency of detectable deletions of 20p12 is low (less than 7%). Progress has been made in the molecular definition of an Alagille syndrome critical region within the short arm of chromosome 20. We will review the clinical, genetic, cytogenetic, and molecular findings in this syndrome.
| S-EPMC1050871 | biostudies-literature
Project description:Background/aimsTo characterise the ocular manifestations of Williams-Beuren syndrome (WBS) and compare these to patients with isolated elastin mediated supravalvular aortic stenosis (SVAS).MethodsFifty-seven patients with a diagnosis of WBS and five with SVAS underwent comprehensive ophthalmic evaluation at the National Institutes of Health from 2017 to 2020, including best-corrected visual acuity, slit-lamp biomicroscopy, optical biometry, dilated fundus examination, optical coherence tomography and colour fundus imaging.ResultsMean age of the 57 WBS patients was 20.3 years (range 3-60 years). Best-corrected visual acuity ranged from 20/20 to 20/400 with mean spherical equivalent near plano OU. Twenty-four eyes (21.8%) had an axial length (AL) less than 20.5 mm and 38 eyes (34.5%) had an AL measuring 20.5-22.0 mm. Stellate iris and retinal arteriolar tortuosity were noted in 30 (52.6%) and 51 (89.5%) WBS patients, respectively. Novel retinal findings in WBS included small hypopigmented retinal deposits (OD 29/57, OS 27/57) and broad foveal pit contour (OD 44/55, OS 42/51). Of the five patients with SVAS, none had stellate iris or broad foveal pit contour while 2/5 had retinal arteriolar tortuosity.ConclusionWBS is a complex multisystem genetic disorder with diverse ophthalmic findings that differ from those seen in isolated elastin mediated SVAS. These results suggest other genes within the WBS critical region, aside from ELN, may be involved in observed ocular phenotypes and perhaps broader ocular development. Furthermore, retinal arteriolar tortuosity may provide future insight into systemic vascular findings in WBS.
| S-EPMC10074447 | biostudies-literature
Project description:Background Despite favorable outcomes of surgical pulmonary artery (PA) reconstruction, isolated proximal stenting of the central PAs is common clinical practice for patients with peripheral PA stenosis in association with Williams and Alagille syndromes. Given the technical challenges of PA reconstruction and the morbidities associated with transcatheter interventions, the hemodynamic consequences of all treatment strategies must be rigorously assessed. Our study aims to model, assess, and predict hemodynamic outcomes of transcatheter interventions in these patients. Methods and Results Isolated proximal and "extensive" interventions (stenting and/or balloon angioplasty of proximal and lobar vessels) were performed in silico on 6 patient-specific PA models. Autoregulatory adaptation of the cardiac output and downstream arterial resistance was modeled in response to intervention-induced hemodynamic perturbations. Postintervention computational fluid dynamics predictions were validated in 2 stented patients and quantitatively assessed in 4 surgical patients. Our computational methods accurately predicted postinterventional PA pressures, the primary indicators of success for treatment of peripheral PA stenosis. Proximal and extensive treatment achieved median reductions of 14% and 40% in main PA systolic pressure, 27% and 56% in pulmonary vascular resistance, and 10% and 45% in right ventricular stroke work, respectively. Conclusions In patients with Williams and Alagille syndromes, extensive transcatheter intervention is required to sufficiently reduce PA pressures and right ventricular stroke work. Transcatheter therapy was shown to be ineffective for long-segment stenosis and pales hemodynamically in comparison with published outcomes of surgical reconstruction. Regardless of the chosen strategy, a virtual treatment planning platform could identify lesions most critical for optimizing right ventricular afterload.
| S-EPMC9075299 | biostudies-literature
Project description:Alagille syndrome (AGS) is a well defined genetic disorder characterised by five major features. An autosomal dominant mode of transmission with reduced penetrance has been suggested by the analysis of a limited number of families. However there has been no statistical analysis. We report here the first segregation analysis of AGS, using 33 families collected through 43 probands. Segregation analysis of these families allowed us to conclude that AGS is transmitted as a dominant disorder with 94% penetrance and 15% of cases are sporadic. The expressivity of the phenotype was variable and 26 persons (15 parents and 11 sibs) were identified as presenting minor forms of the disease. These results are valuable for genetic counselling.
| S-EPMC1049922 | biostudies-other
Project description:BackgroundAlagille syndrome (ALGS) is a dominant, multisystem disorder caused by mutations in the Jagged1 (JAG1) ligand in 94% of patients, and in the NOTCH2 receptor in <1%. There are only two NOTCH2 families reported to date. This study hypothesised that additional NOTCH2 mutations would be present in patients with clinical features of ALGS without a JAG1 mutation.MethodsThe study screened a cohort of JAG1-negative individuals with clinical features suggestive or diagnostic of ALGS for NOTCH2 mutations.ResultsEight individuals with novel NOTCH2 mutations (six missense, one splicing, and one non-sense mutation) were identified. Three of these patients met classic criteria for ALGS and five patients only had a subset of features. The mutations were distributed across the extracellular (N=5) and intracellular domains (N=3) of the protein. Functional analysis of four missense, one nonsense, and one splicing mutation demonstrated decreased Notch signalling of these proteins. Subjects with NOTCH2 mutations demonstrated highly variable expressivity of the affected systems, as with JAG1 individuals. Liver involvement was universal in NOTCH2 probands and they had a similar prevalence of ophthalmologic and renal anomalies to JAG1 patients. There was a trend towards less cardiac involvement in the NOTCH2 group (60% vs 100% in JAG1). NOTCH2 (+) probands exhibited a significantly decreased penetrance of vertebral abnormalities (10%) and facial features (20%) when compared to the JAG1 (+) cohort.ConclusionsThis work confirms the importance of NOTCH2 as a second disease gene in ALGS and expands the repertoire of the NOTCH2 related disease phenotype.
| S-EPMC3682659 | biostudies-literature
Project description:In the nearly 50 years since the description of Williams syndrome by [Williams et al. (1961); Circulation 24:1311-1318], the focus of scientific inquiry has shifted from identification, definition, and description of the syndrome in small series to genotype-phenotype correlation, pathophysiologic investigation in both humans and in animal models, and therapeutic outcomes in large cohorts. Study of this rare syndrome has provided insight into the structure and function of the extracellular matrix, has contributed to understanding of genomic structure and rearrangement, and is beginning to elucidate genetic underpinnings of learning, language, and behavior. The results of current research not only recommend interventions that can be implemented now, but also identify areas requiring additional investigation, and suggest future therapeutic approaches.
| S-EPMC2946897 | biostudies-literature