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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Williams syndrome first described in 1961 is generally characterised by mental deficiency, gregarious personality, unusual "elfin" facies, supravalvular aortic stenosis and idiopathic infantile hypercalcaemia. Patients with Williams syndrome show a hemizygous submicroscopic deletion of 7q11.23 detectable by fluorescent in-situ hybridisation (FISH). The deleted portion of the chromosome corresponds to the Elastin gene. We report 3 girls with characteristics of Williams syndrome in whom the diagnosis was confirmed by demonstration of the hemizygous deletion of 7q11.23 in the karyotype by FISH. These patients, aged 6, 7 and 10 years, showed the characteristic facies and gregarious personalities. Some developmental delay with mild mental deficiency and dysmorphic facies were prominent features in the initial presentation. Cardiac lesions found in these patients were small patent ductus arteriosus which closed, pulmonary valvular stenosis and mitral valve prolapse associated with mitral regurgitation respectively. Hypercalcaemia was not documented in these patients. Learning difficulty was a major issue and all patients required special schooling. Chromosome analyses done on peripheral blood were found to be normal in all patients. FISH using the Elastin Williams Syndrome Chromosome Region (WSCR) probes (oncor) showed the hemizygous deletion of 7q11.23. Diagnosis of Williams syndrome can now be confidently confirmed with the help of FISH.
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PMID:Williams syndrome--the Singapore General Hospital experience. 928 33

Williams' syndrome (WS) is a rare genetic condition of autosomal dominant inheritance with varying penetrance, which consists of supravalvular aortic stenosis, a characteristic dysmorphic facies named "elf face", mental retardation and other clinical manifestations including transient infantile idiopathic hypercalcemia, growth retardation, and frequent dental problems. It usually presents sporadically, and there are only a few cases of family involvement reported in the literature. Recent studies show that mutations in the elastin gene at chromosome 7q11.23, which occur approximately in 90% of cases, could be the cause of the different clinical manifestations in this syndrome. In this paper we report a case of family involvement with five family members involved with WS (three siblings, the mother, and the siblings' maternal uncle) and all had cardiac structural disorders (supravalvular aortic stenosis being the most frequent), a characteristic face and a low intellectual coefficient. The complementary tests included blood chemistry, chest X-ray, and echocardiogram, which led to the diagnosis of the associated valve pathology. Three patients required therapeutic catheterism with Stent valve implant and valve prosthetic replacement to control cardiac manifestations.
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PMID:[William's syndrome. Report of a case with family involvement]. 955 23

Williams syndrome (WS) is a neurodevelopmental disorder with a variable phenotype. Molecular genetic studies have indicated that hemizygosity at the elastin locus (ELN) may account for the cardiac abnormalities seen in WS, but that mental retardation and hypercalcemia are likely caused by other genes flanking ELN. In this study, we defined the minimal critical deletion region in 63 patients using 10 microsatellite markers and 5 fluorescence in situ hybridization (FISH) probes on chromosome 7q, flanking ELN. The haplotype analyses showed the deleted cases to have deletions of consistent size, as did the FISH analyses using genomic probes for the known ends of the commonly deleted region defined by the satellite markers. In all informative cases deleted at ELN, the deletion extends from D7S489U to D7S1870. The genetic distance between these two markers is about 2 cM. Of the 51 informative patients with deletions, 29 were maternal and 22 were paternal in origin. There was no evidence for effects on stature by examining gender, ethnicity, cardiac status, or parental origin of the deletion. Heteroduplex analysis for LIMK1, a candidate gene previously implicated in the WS phenotype, did not show any mutations in our WS patients not deleted for ELN. LIMK1 deletions were found in all elastin-deletion cases who had WS. One case, who has isolated, supravalvular aortic stenosis and an elastin deletion, was not deleted for LIMK1. It remains to be determined if haploinsufficiency of LIMK1 is responsible in part for the WS phenotype or is simply deleted due to its close proximity to the elastin locus.
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PMID:Delineation of the common critical region in Williams syndrome and clinical correlation of growth, heart defects, ethnicity, and parental origin. 963 30

Williams syndrome (WS) is a developmental disorder caused by haploinsufficiency of genes at 7q11.23. We have shown that hemizygosity of elastin is responsible for one feature of WS, supravalvular aortic stenosis. We have also implicated LIM-kinase 1 hemizygosity as a contributing factor to impaired visual-spatial constructive cognition in WS. Here we identify and characterize a novel gene, FKBP6, within the common WS deletion region. FKBP6 shows homology to the FK-506 binding protein (FKBP) class of immunophilins. FKBP6 has a putative N-terminal FK-506 binding and peptidylproyl isomerase (rotamase) domain and, like known high-molecular-weight FKBPs, an imperfect C-terminal tetratricopeptide repeat domain. FKBP6 is expressed in testis, heart, skeletal muscle, liver, and kidney. FKBP6 consists of nine exons and is completely contained within a 35-kb cosmid clone. Fluorescence in situ hybridization experiments show that FKBP6 gene is deleted in 40/40 WS individuals. Hemizygous deletion of FKBP6 may contribute to certain defects such as hypercalcemia and growth delay in WS.
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PMID:A novel human gene FKBP6 is deleted in Williams syndrome. 978 77

The Williams syndrome is a relatively rare disease with characteristic facial appearance, mental retardation, growth deficiency, cardiovascular anomalies, hypercalcemia and multiple organic dysfunctions. However, the urological findings of this syndrome (positive in up to 40% of patients) have not been frequently discussed. We present the case of a 6 year-old white girl with this diagnosis and a 3-year history of urinary incontinence. The investigation revealed bladder diverticula and detrusor hyperactivity, which was successfully treated with oxibutimin. We stress the importance of urological investigation, describe the main findings and discuss the pathophysiology and management, which significantly improves the quality of life of these children.
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PMID:[Neuro-urological findings in Williams syndrome: report of a case]. 985 Jul 71

Williams syndrome (WS) is a contiguous gene deletion disorder caused by haploinsufficiency of genes at 7q11.23. We have shown that hemizygosity of elastin is responsible for one feature of WS, supravalvular aortic stenosis (SVAS). We have also implicated LIM-kinase 1 hemizygosity as a contributing factor to impaired visual-spatial constructive cognition in WS. However, the common WS deletion region has not been completely characterized, and genes for additional features of WS, including mental retardation, infantile hypercalcemia, and unique personality profile, are yet to be discovered. Here, we present a physical map encompassing 1.5 Mb DNA that is commonly deleted in individuals with WS. Fluorescence in situ hybridization analysis of 200 WS individuals shows that WS individuals have the consistent deletion interval. In addition, we identify three novel genes from the common deletion region: WS-betaTRP, WS-bHLH, and BCL7B. WS-betaTRP has four putative beta-transducin (WD40) repeats, and WS-bHLH is a novel basic helix-loop-helix leucine zipper (bHLHZip) gene. BCL7B belongs to a novel family of highly conserved genes. We describe the expression profile and genomic structure for each of these genes. Hemizygous deletion of one or more of these genes may contribute to developmental defects in WS.
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PMID:Complete physical map of the common deletion region in Williams syndrome and identification and characterization of three novel genes. 986 Mar 2

Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder, characterized by distinct facial changes, growth deficiency, mental retardation, supravalvular aortic stenosis (SVAS)/peripheral pulmonary stenosis, and associated at times with infantile hypercalcemia. A pilot study has been carried out to assess the reliability of the detection of hemizygosity at the elastin locus by fluorescence in situ hybridization (FISH) analysis as a diagnostic test in both classical and atypical WBS. Eight subjects with classical WBS and four others in whom a diagnosis could not be confirmed on clinical criteria alone were enrolled. In the classical WBS group, five (5/8) had a visible interstitial 7q11.22-11.23 deletion detected by high-resolution banding, and all (8/8) had a submicroscopic deletion of the elastin locus on chromosome 7 by FISH analysis. In the atypical WBS group, only one (1/4) had elastin deletion. The other three, with isolated SVAS, had normal development and minimal signs of WBS. Furthermore, the patients with microscopic 7q11.22-11.23 deletion have more associated features of WBS than those without visible interstitial deletions by high-resolution banding. These results, therefore, emphasize the importance of a combined high-resolution and molecular cytogenetic (i.e., FISH) approach to diagnosis and suggest that the degree to which microscopic/submicroscopic deletions of chromosome 7 extending in beyond the elastin locus may explain some of the phenotypical variability found in WBS.
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PMID:FISH analysis in both classical and atypical cases of Williams-Beuren syndrome. 992 15

Previous studies report conflicting frequencies of hypertension in cohorts of patients with Williams syndrome (WS). We studied blood pressure (BP) in WS using 24-hour ambulatory BP monitoring. This technique reliably measures day- and nighttime BP in a subject's natural environment and provides better prognostic information on long-term risks of hypertension than casual BP determinations. Twenty WS subjects evaluated through a multidisciplinary WS clinic and 35 age and gender-matched controls were studied. We found that WS subjects had significantly higher ambulatory BP than controls. After controlling for age, sex, and weight, the diagnosis of WS added approximately 10 mmHg to mean daytime and nighttime BPs. Hypertension, as defined by elevated mean daytime BP, was present in 40% of WS subjects versus 14% of controls (P < 0.05); among the children studied this difference was even more dramatic with 46% of WS children versus 6% of control children classified as hypertensive (P = 0.01). We also demonstrated normal diurnal BP variation but no evidence of a "white coat" effect or increased BP variability. Interestingly, parental reporting of a history of infantile hypercalcemia was strongly associated with the presence of hypertension (P = 0.008). Our data demonstrate that both children and adults with WS have higher mean BP and higher frequency of hypertension than healthy controls. Thus, elevated BP readings in the office setting should not be dismissed but require more thorough assessment.
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PMID:Elevated ambulatory blood pressure in 20 subjects with Williams syndrome. 1023 42

Williams-Beuren syndrome is an autosomal dominant disorder resulting from a submicroscopic deletion of contiguous genes on the long arm of chromosome 7. It consists of a variety of hallmark physical features, which include distinctive facial characteristics, cardiac anomalies (of which the most common is supravalvular aortic stenosis), and occasional idiopathic hypercalcemia. The condition also includes a unique cognitive profile, with relative sparing of language and facial recognition skills against a background of mental retardation. This paper reviews the early history and clinical experience with this syndrome, how it unfolds from infancy through adulthood, and how it manifests in different organ systems. Evidence-based recommendations are then offered for the treatment of the specific developmental and medical issues that arise in patients with Williams syndrome.
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PMID:Williams-Beuren syndrome: an update and review for the primary physician. 1032 75

Williams syndrome (WS) is a contiguous gene syndrome caused by hemizygosity for a chromosomal deletion at 7q11.23. The range of phenotypes includes mental retardation, dysmorphic facies, heart abnormalities, short stature, a specific cognitive profile, hyperacusis, and infantile hypercalcaemia. To identify all the deleted genes, we have constructed a detailed physical map and complete BAC/PAC contig of the critical region, extending a distance of approximately 2 Mb and delimited by the nondeleted markers D7S1816 and D7S489A. Somatic cell hybrids of WS patients were made and used to define the centromeric and telomeric deletion breakpoints, enabling the size of the WS deletion to be defined as approximately 1.4 Mb. Genes previously mapped to the region have been located on the contig, and we have isolated eight transcripts, two of which have been characterized as the genes CPETR1 and CPETR2. This contig and expressed sequence map will form the basis for the construction of a complete transcription map of the deleted region and will enable genotype-phenotype correlations to be attempted to identify the individual components of WS.
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PMID:A complete physical contig and partial transcript map of the Williams syndrome critical region. 1036 45


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