Get your own Free Home PageRecord 1The genetic basis of pediatric cardiovascular disease. Strauss AW; Johnson MC Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA. Semin Perinatol (UNITED STATES) Dec 1996, 20 (6) p564-76, ISSN 0146-0005 Languages: ENGLISH Document type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
Congenital heart disease (CHD), cardiomyopathy, and vasculopathies are common causes of mortality and morbidity in pediatrics, including the perinatal period. This article reviews evidence that single gene defects cause many of the pediatric heart diseases. Vasculopathies discussed include Marfan's syndrome, supravalvar aortic stenosis and Williams' syndrome, Alagille's syndrome, and hereditary telangiectasia, the Osler-Weber-Rendu syndrome. Genetic causes of hypertrophic cardiomyopathy caused by sarcomeric protein mutations (beta-cardiac myosin heavy chain) and of dilated cardiomyopathy secondary to structural protein deficiencies (dystrophin) are presented. Defects in proteins essential for myocardial energy production such as oxidative phosphorylation proteins and fatty acid oxidation genes that cause cardiomyopathy or sudden death are described. Gene ablation models in mice, such as RXR alpha and homeobox gene knockouts, which result in cardiac phenotypes resembling human congenital heart disease, are described. Familial types of human CHD which are being investigated for genetic causes by positional cloning methods and known cytogenetic causes of CHD, including the CATCH-22 syndrome and monosomy at 22q11, are presented. General lessons and principles derived from these new and exciting discoveries in human cardiovascular development are surmised. (78 Refs.)
Record 2(A successful surgical repair of total anomalous pulmonary venous connection associated with Williams syndrome) Shimamoto T; Ikeda T; Koshiji T; Nishimura K; Nomoto S; Matsuda K; Ban T Department of Cardiovascular Surgery, School of Medicine, Kyoto University, Japan. Kyobu Geka (JAPAN) May 1997, 50 (5) p405-8, ISSN 0021-5252 Languages: JAPANESE Summary Languages: ENGLISH Document type: JOURNAL ARTICLE English Abstract
The surgical correction was performed successfully in a 14-year-old boy with total anomalous pulmonary venous connection (type Ia) associated with Williams syndrome. The diagnosis was made at the age of 3 and he had been well until the age of 13 when sudden chordal rupture caused severe mitral regurgitation and supraventricular tachyarrhythmia. The operational procedure includes common pulmonary vein and left atrium anastomosis through Gersony-Malm approach, chordal reconstruction of mitral valve with 4-0 Core Tex sutures. His postoperative course has been well without the sign of venous obstruction. As far as we know, this is the first documentation of a case of Williams syndrome associated with total anomalous pulmonary venous connection.
Record 3Pseudohypertension and Williams syndrome (letter). Bastianon V Pediatr Cardiol (UNITED STATES) Mar-Apr 1996, 17 (2) p132, ISSN 0172-0643 Languages: ENGLISH Document type: LETTER
Record 4Supravalvular aortic stenosis, pulmonary artery stenosis, and coronary artery stenosis in twins. Nakanishi T; Iwasaki Y; Momma K; Imai Y Pediatric Cardiology, Heart Institute of Japan, Tokyo Women's Medical College, Japan. Pediatr Cardiol (UNITED STATES) Mar-Apr 1996, 17 (2) p125-8, ISSN 0172-0643 Languages: ENGLISH Document type: JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES Supravalvular aortic stenosis (SVAS) is rare in twins. We report monozygotic twins, both of whom had SVAS, coronary ostial stenosis, and peripheral pulmonary arterial stenosis, but no other phenotypic features of Williams syndrome. One of the twins died suddenly, but the SVAS and the right and left coronary ostial stenoses were enlarged successfully at operation in the other twin. (12 Refs.)
Record 5Functional analysis of episodic self-injury correlated with recurrent otitis media. O'Reilly MF Department of Psychology, University College Dublin, Belfield, Ireland. [email protected] J Appl Behav Anal (UNITED STATES) Spring 1997, 30 (1) p165-7, ISSN 0021-8855 Languages: ENGLISH Document type: JOURNAL ARTICLE
A functional analysis examined the consequences that maintained episodic self-injury and the relationship between those consequences and otitis media for a child with moderate developmental disabilities. Results indicated that self-injury occurred only during periods of otitis media. Otitis media may have served as an establishing operation related to escape from ambient noise.
Record 6A novel human homologue of the Drosophila frizzled wnt receptor gene binds wingless protein and is in the Williams syndrome deletion at 7q11.23. Wang YK; Samos CH; Peoples R; Perez-Jurado LA; Nusse R; Francke U Howard Hughes Medical Institute, Stanford University Medical Center, CA 94305, USA. Hum Mol Genet (ENGLAND) Mar 1997, 6 (3) p465-72, ISSN 0964-6906 Languages: ENGLISH Document type: JOURNAL ARTICLE
Williams syndrome (WS) is a developmental disorder with a characteristic personality and cognitive profile that is associated, in most cases, with a 2 Mb deletion of part of chromosome band 7q11.23. By applying CpG island cloning methods to cosmids from the deletion region, we have identified a new gene, called FZD3. Dosage blotting of DNA from 11 WS probands confirmed that it is located within the commonly deleted region. Sequence comparisons revealed that FZD3, encoding a 591 amino acid protein, is a novel member of a seven transmembrane domain receptor family that are mammalian homologs of the Drosophila tissue polarity gene frizzled. FZD3 is expressed predominantly in brain, testis, eye, skeletal muscle and kidney. Recently, frizzled has been identified as the receptor for the wingless (wg) protein in Drosophila. We show that Drosophila as well as human cells, when transfected with FZD3 expression constructs, bind Wg protein. In mouse, the wg homologous Wnt1 gene is involved in early development of a large domain of the central nervous system encompassing much of the midbrain and rostral metencephalon. The potential function of FZD3 in transmitting a Wnt protein signal in the human brain and other tissues suggests that heterozygous deletion of the FZD3 gene could contribute to the WS phenotype.
Record 7Magnetic resonance imaging of the brain in Williams-Beuren syndrome (letter) Brinkmann G; Heller M; Partsch CJ; Gosch A; Pankau R Am J Med Genet (UNITED STATES) Jan 20 1997, 68 (2) p243, ISSN 0148-7299 Languages: ENGLISH Document type: LETTER
Record 8Brief report: response to methylphenidate in two children with Williams syndrome. Power TJ; Blum NJ; Jones SM; Kaplan PE University of Pennsylvania School of Medicine, USA. J Autism Dev Disord (UNITED STATES) Feb 1997, 27 (1) p79-87, ISSN 0162-3257 Languages: ENGLISH Document type: CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
Record 9Genotype-phenotype correlation in two sets of monozygotic twins with Williams syndrome. Castorina P; Selicorni A; Bedeschi F; Dalpra L; Larizza L Department of Biology and Genetics, Medical Faculty, University of Milan, Italy. Am J Med Genet (UNITED STATES) Mar 3 1997, 69 (1) p107-11, ISSN 0148-7299 Languages: ENGLISH Document type: JOURNAL ARTICLE
We report on two sets of monozygotic (MZ) twins with Williams syndrome (WS), following the 6 pairs already reported in the literature. We have confirmed monozygosity of both pairs of twins by DNA microsatellite analysis and the clinical diagnosis by fluorescence in situ hybridization using a WS-specific probe. Analysis of the concordance of different clinical signs between members of each pair of twins benefitted from a lengthy clinical follow-up, from 24 months to 7 years in one pair, and from the age of 15 years with reevaluation after 2 years in the other pair. Most clinical signs were concordant in the twins of each pair, with differences present at younger ages, mainly minor facial anomalies, being attenuated with time. Developmental delay was substantially concordant, but the degree differed slightly between twins in each pair. Inguinal hernia was present in a single twin in pair 1. Facial anomalies and other signs attributable to connective tissue abnormalities were also displayed by only one twin in both sets, suggesting that the WS genotype has only a predisposing role in the development of these signs.
Record 10Independence and adaptive behavior in adults with Williams syndrome. Davies M; Howlin P; Udwin O School of Psychology, Queen's University of Belfast, Northern Ireland. Am J Med Genet (UNITED STATES) May 16 1997, 70 (2) p188-95, ISSN 0148-7299 Languages: ENGLISH Document type: JOURNAL ARTICLE
This study describes the adjustment of 70 adults with Williams syndrome, in terms of self-help skills, independence, and occupational levels. Although the overall mean IQ of the group (62.00) was within the mild mental handicap range, relatively few individuals were able to attain a high level of independence or cope with the demands of employment. Adaptive behavior scores were significantly below chronological age. Outcome measures were compared with available data on other groups of adults of similar age and level of intellectual impairment. Implications for the community care of adults with Williams syndrome are discussed.
Record 11A tetranucleotide repeat polymorphism within the human elastin gene (ELNi1). Urban Z; Csiszar K; Fekete G; Boyd CD Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, USA. Clin Genet (DENMARK) Feb 1997, 51 (2) p133-4, ISSN 0009-9163 Languages: ENGLISH Document type: JOURNAL ARTICLE
Record 12(Extended aortoplasty for supravalvular aortic stenosis with Williams syndrome) Nagasaka S; Taniguchi S; Kawata T; Mizuguchi K; Kawachi K; Kitamura S Department of Surgery III, Nara Medical College, Japan. Nippon Kyobu Geka Gakkai Zasshi (JAPAN) Apr 1997, 45 (4) p601-6, ISSN 0369-4739 Languages: JAPANESE Summary Languages: ENGLISH Document type: JOURNAL ARTICLE English Abstract
We report a male case of supravalvular aortic stenosis associated with Williams syndrome requiring surgery at age 11. At 5 years of age, this boy presented with a harsh systolic heart murmur and was diagnosed as having a supravalvular aortic stenosis. In association with mental retardation, elfin face and bilateral inguinal hernias, he was diagnosed as a Williams syndrome confirmed by the chromosomal analysis revealing the deletion of 7q11.23. The pressure gradient across the stenotic lesion of the ascending aorta, which had been 35 mmHg at age 5, progressed to 80 mmHg at age 11 years. Extended aortoplasty was performed using a patch of 20 mm Hemashield graft prosthesis. Postoperative cardiac catheterization confirmed that the pressure gradient in the ascending aorta completely disappeared following surgery.
Record 13Language and Williams syndrome: how intact is "intact"? Karmiloff-Smith A; Grant J; Berthoud I; Davies M; Howlin P; Udwin O MRC-CDU, London, U.K. [email protected] Child Dev (UNITED STATES) Apr 1997, 68 (2) p246-62, ISSN 0009-3920 Languages: ENGLISH Document type: JOURNAL ARTICLE
It has been claimed that Williams syndrome (WS), a rare neurodevelopmental disorder, is characterized by serious cognitive deficits alongside intact language. The syndrome is often used as a prime example of the modularity of an innate faculty for morphosyntactic rules. We challenge this claim and hypothesize that morphosyntax, although surprisingly good given WS level of mental retardation, is by no means intact. We make an initial test of this hypothesis through an analysis of the receptive language of a group of English-speaking WS individuals on a standardized morphosyntactic test. We then present an experimental study of expressive language that examines grammatical gender assignment in French-speaking WS patients. Despite a Verbal Mental Age selected to be higher than the chronological age of the young control group, these people with WS continue even in adulthood to show clear-cut deficits in their production of an aspect of morphosyntax that normal children acquire effortlessly very early. The results of the 2 studies, one focusing on receptive language and the other on expressive language, challenge the notion that comprehension and use of morphosyntactic rules in WS individuals are intact. The Within-domain dissociations regarding the use of grammatical gender assignment across several sentence clements and their difficulties in understanding embedded sentences-two quintessentially linguistic skills-suggest that we must rethink the notion of spared, modular, language capacities in Williams syndrome. We conclude that WS language follows a different path to normal acquisition and may turn out to be more like second language learning.
Record 14Chromosome abnormalities in congenital heart disease. Johnson MC; Hing A; Wood MK; Watson MS Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA. Am J Med Genet (UNITED STATES) Jun 13 1997, 70 (3) p292-8, ISSN 0148-7299 Languages: ENGLISH Document type: JOURNAL ARTICLE
Refinements in cytogenetic techniques have promoted progress in understanding the role that chromosome abnormalities play in the cause of congenital heart disease. To determine if mutations at specific loci cause congenital heart disease, irrespective of the presence of other defects, and to estimate the prevalence of chromosome abnormalities in selected conotruncal cardiac defects, we reviewed retrospectively cytogenetic and clinical databases at St. Louis Children's Hospital. Patients with known 7q11.23 deletion (Williams syndrome), Ullrich-Turner syndrome (UTS), and most autosomal trisomies were excluded from this analysis. Two groups of patients were studied. Over a 6.5-year period, 57 patients with chromosomal abnormalities and congenital heart disease were identified. Of these, 37 had 22q11 deletions; 5 had abnormalities of 8p; and 15 had several other chromosome abnormalities. The prevalence of chromosome abnormalities in selected conotruncal or aortic arch defects was estimated by analysis of a subgroup of patients from a recent 22-month period. Chromosome abnormalities were present in 12% of patients with tetralogy of Fallot, 26% in tetralogy of Fallot/pulmonary atresia, 44% in interrupted aortic arch, 12% in truncus arteriosus, 5% in double outlet right ventricle, and 60% in absent pulmonary valve. We conclude that chromosome analysis should be considered in patients with certain cardiac defects. Specifically, fluorescent in situ hybridization (FISH) analysis of 22q11 is indicated in patients with conotruncal defects or interrupted aortic arch. High resolution analysis should include careful evaluation of the 8p region in patients with either conotruncal or endocardial cushion defects.
Record 15Williams-Beuren syndrome. Long-term results of surgical treatments in six patients. Actis Dato GM; La Torre M; Caimmi P; Actis Dato A Jr; Centofanti P; Ottino GM; Di Summa M talian Institution of Cardiac Surgery, Turin, Italy. J Cardiovasc Surg (Torino) (ITALY) Apr 1997, 38 (2) p125-9, ISSN 0021-9509 Languages: ENGLISH Document type: JOURNAL ARTICLE
To settle long-term outcome after surgery for supravalvular aortic stenosis in the Williams-Beuren syndrome, we reviewed the records of 6 patients who had repair of the localized form (n = 5) or diffuse form (n = 1) at our Institution from 1965 to 1971. Four patients were females and 2 males, ages at operation ranged from 9 to 16 years (mean = 13 +/- 2.37 years). In all the patients was present the typical elfin facies with mental retardation and reduced I.Q. Preoperative omeral pressure was different between left and right arm (89 +/- 7/67 +/- 8 vs 105 +/- 8/77 +/- 4). Chest X-ray showed and enlargement of the cardia silhouette in all the patients. Cardiac catheterization, performed in all the patients, allowed diagnosis of supravalvular aortic stenosis and, in one case of subaortic stenosis associated. Intraoperatively a coronary tree enlargement was found in all cases with particular involvement of the right coronary in two patients. The mean diameter of the ascending aorta was 5.67 +/- 1.97 mm but the smallest (3 mm) was in the diffuse group. In group with localized stenosis the aortic root was enlarged with a teardrop patch in Dacron (n = 4) or a simple transverse suture after a longitudinal incision (n = 1). A pantaloon-shaped patch was necessary in the diffuse form case. There were no operative deaths and all the patients were discharged from the hospital after 2 weeks. A clinical follow-up was possible in all the patients (10%) extended from 25 to 30 years (mean = 27.7 +/- 2.19 years); there were no late deaths and at presents time the mean age of the patient is 40 +/- 3 years. All patients were in functional class I or II. There was no significant difference between patients with a teardrop-shaped or pantaloon-shaped patch in terms of late gradient, survival, or aortic insufficiency studied by Echocardiography and color-Doppler. Of six patients two are living with parents or relatives but four are in a farm-college for disable people working and having some responsibility. We conclude that surgery for the correction of supravalvular aortic stenosis in Williams-Beuren syndrome is mandatory and both the procedures with patch techniques provide excellent long-term results of gradients and aortic valve competence. Moreover the patients after the operation can have a normal activity with a satisfactory style and expectation of life.
Record 16Cloning and biochemical characterization of LIMK-2, a protein kinase containing two LIM domains. Smolich B; Vo M; Buckley S; Plowman G; Papkoff J SUGEN, Inc, Redwood City, CA 94063, USA. [email protected] J Biochem (Tokyo) (JAPAN) Feb 1997, 121 (2) p382-8, ISSN 0021-924X Languages: ENGLISH Document type: JOURNAL ARTICLE
We have isolated human and rat clones of the LIM motif-containing protein kinase, termed LIMK-2. LIMK-2 is related to the neuronally expressed LIM-kinase, whose hemizygous deletion appears to result in cognitive impairment in patients with Williams syndrome. The hallmark of this protein family is the presence of 1 or 2-terminal LIM motifs and an atypical C-terminal protein kinase domain. LIMK-2 mRNA was detected by Northern blot analysis in human tissues, most abundantly in placenta, lung, liver, and pancreas, and also in a variety of cell lines including neuronal, glioblastoma, and mammary carcinoma lines. The LIMK-2 transcript was also induced upon neuroectodermal differentiation of mouse P19 embryonal carcinoma cells. A 65 kDa recombinant LIMK-2 protein was identified in 293 cells stably transfected with a LIMK-2 expression vector. An in vitro kinase assay demonstrates LIMK-2 is autophosphorylated and exhibits serine/threonine kinase activity towards the exogenous substrate MBP. The endogenous 65 kDa LIMK-2 protein was detected in a variety of cell lines, and coprecipitates with a 140 kDa tyrosine phosphorylated protein, but was not itself tyrosine phosphorylated. At the subcellular level, LIMK-2 is localized in both the nucleus and in a Triton X-100 soluble fraction.
Record 17Aortic stenosis in children: 19-year experience. Liu CW; Hwang B; Lee BC; Lu JH; Meng LC Department of Pediatrics, Veterans General Hospital-Taipei, Taiwan, R.O.C. Chung Hua I Hsueh Tsa Chih (Taipei) (TAIWAN) Feb 1997, 59 (2) p107-13, ISSN 0578-1337 Languages: ENGLISH Document type: JOURNAL ARTICLE
BACKGROUND: In the Taiwanese literature, few articles describe the pertinent features of aortic stenosis (AS). This study explores the features of AS in Chinese children. METHODS: 3808 children with congenital heart diseases have undergone cardiac catheterization at our institution over the past 19 years. Among them, 51 (1.3%) cases were AS. The clinical, electrocardiographic, echocardiographic and catheterization findings, the methods of treatment and outcomes were reviewed. RESULTS: Valvular AS occurred in 39 children (76.5%), subvalvular AS in 5 (9.8%), and supravalvular AS in 7(13.7%). Male was predominant (M/F ratio, 2.6) except in supravalvular type. Forty-three patients had associated cardiovascular defects. Aortic regurgitation (AR) was the most common one. Most patients (56.9%) were asymptomatic. Classic symptoms included exertional dyspnea (17.6%), syncope (9.8%), and chest pain (7.8%), etc. Left ventricular hypertrophy was noted in 31.2% of cases. The mean duration of follow-up was 3.9 +/- 3.4 years. Ten patients received open-heart surgery and 2 received balloon dilation. The pressure gradients across the stenotic area dropped from 95.3 +/- 29.3 to 51.4 +/- 35.8 and 53.1 +/- 12.3 mm Hg in early and late Doppler follow-up studies, respectively (p < 0.05). The average gradient increased from 36.9 +/- 25.3 to 40.8 +/- 32.6 mm Hg in nonsurgical patients. The result was insignificant. No mortality occurred following open-heart surgery. One child expired due to heart failure after the ligation of the patent ductus arteriosus and dilation of the stenotic aortic valve on the surgical table under general anesthesia. Autopsy revealed valvular rupture. In the nonsurgical group, no mortality occurred, but one patient was brought home by parents in critical condition and later died. CONCLUSIONS: We found that some clinical features of AS in Chinese children were different from those in occidental populations. (1) The incidence of AS was relatively low. (2) Subvalvular AS was the least common type in contrast to supravalvular AS in western studies. (3) Male predominance was not present in the supravalvular type, which lacked sexual proclivity. (4) Williams syndrome was a more frequently associated anomaly. Turner syndrome was not present in our study. (5) Isolated AS was less frequent. (6) The unusual finding such as right ventricular hypertrophy on EKG was present due to associated cardiac anomalies. Open-heart surgery is effective and safe, but the efficacy of balloon dilation requires further investigation.
Record 18Behavioural phenotypes and family stress in three mental retardation syndromes. Sarimski K Kinderzentrum, Munchen, Germany. Eur Child Adolesc Psychiatry (GERMANY) Mar 1997, 6 (1) p26-31, ISSN 1018-8827 Languages: ENGLISH Document type: JOURNAL ARTICLE
The behavioural phenotype of 30 fragile-X, 35 Prader-Willi and 35 Williams-Beuren syndrome children was explored using a psychometric approach. Results confirmed some distinct behaviours as syndrome-specific, but revealed a high degree of within-syndrome variability and overlap between syndromes as well. Parental stress was high in each of the groups, but was mediated by maternal dissatisfaction with family relationships. A multimethod approach with detailed syndrome-specific observations is recommended for further research.
Record 19Aortic stiffness with the Williams-Beuren syndrome [letter] Wessel A; Pankau R; Berdau W; Lons P Pediatr Cardiol (UNITED STATES) May-Jun 1997, 18 (3) p244, ISSN 0172-0643 Languages: ENGLISH Document type: LETTER
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