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Background
Williams syndrome is a rare disorder characterized by physical and developmental problems including an impulsive and overfriendly personality, limited spatial skills and motor control, and intellectual disability. Other features include characteristic "elfin-like" facial features, heart and blood vessel problems, hypercalcemia (elevated blood calcium levels), low birth weight, slow weight gain, feeding problems, irritability during infancy, dental and kidney abnormalities, hyperacusis (sensitive hearing), and musculoskeletal problems. IQs are usually below average, and they are considered moderately to mildly retarded. Most individuals with Williams syndrome have a deletion of genetic material on chromosome 7.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Williams-Beuren syndrome Differences by sex in cardiovascular disease in Williams syndrome.
Sadler LS, Pober BR, Grandinetti A, Scheiber D, Fekete G, Sharma AN, Urban Z.
Division of Genetics, Children's Hospital of Buffalo, New York.
J Pediatr 2001 Dec;139(6):849-853 Abstract quote
OBJECTIVE: To analyze the incidence and severity of cardiovascular disease in patients with Williams syndrome (WS) and to identify factors contributing to its variable expression.
METHODS: Clinical data on patients with WS were collected from several WS centers. Elastin gene deletions were confirmed in all patients. Age at diagnosis, growth data, and cardiovascular diagnoses were recorded retrospectively. Cardiac diagnoses were made on the basis of echocardiographic data. The severity of supravalvular aortic stenosis was recorded by using a 4-step scale (none, mild, moderate, severe).
RESULTS: Statistical analysis of the data revealed that the severity of both supravalvular aortic stenosis and total cardiovascular disease was significantly greater in male patients than female patients (P <.002 and P <.002, respectively; Kruskal-Wallis rank-sum test). This difference was not accounted for by differences in height, weight, body mass index, or head circumference. The clinical diagnosis of WS was made at a significantly younger age in male patients (P <.01, Student t test). Earlier diagnosis was partly because of increased incidence and severity of cardiovascular disease. Another determinant of early diagnosis was low body mass index.
CONCLUSION: Penetrance and severity of the elastin arteriopathy in patients with WS is affected by sex. We hypothesize that differences by sex in arterial stenoses may be related to prenatal hormonal effects. Future epidemiologic and in vitro studies may provide additional insight into the pathogenetic mechanisms of these observed differences.
DISEASE ASSOCIATIONS CHARACTERIZATION Increased prevalence of urinary symptoms and voiding dysfunction in Williams syndrome.
Schulman SL, Zderic S, Kaplan P.
Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, USA.
J Pediatr 1996 Sep;129(3):466-9 Abstract quote
Thirteen of 41 patients (32%) with Williams syndrome in a multidisciplinary clinic were noted to have genitourinary symptoms.
The predominant features were increased urinary frequency and daytime wetting. Four patients had bladder diverticula and uninhibited detrusor contractions as demonstrated on urodynamic studies. We speculate that there may be an association between increased detrusor pressure, an abnormal bladder matrix, and the presence of diverticula.
Early detection of urinary dysfunction through clinical symptoms and appropriate urodynamic studies, with institution of bladder training and anticholinergic medication can improve the patients' voiding patterns, both medically and socially.
Coeliac disease in Williams syndrome.
Giannotti A, Tiberio G, Castro M, Virgilii F, Colistro F, Ferretti F, Digilio MC, Gambarara M, Dallapiccola B.
Servizio di Genetica Medica, Ospedale Bambino Gesu, IRCCS, Piazza S Onofrio 4, 00165, Roma, Italy
J Med Genet 2001 Nov;38(11):767-8 Abstract quote
BACKGROUND: Coeliac disease (CD) has been reported in several patients affected by chromosomal disorders, including Down syndrome (DS) and Turner syndrome (TS). CD has also been found in sporadic Williams syndrome (WS) patients. In this study, CD was evaluated in a consecutive series of patients with WS, in order to estimate if the prevalence of CD in WS patients is higher than in the general population.
METHODS AND RESULTS: A consecutive series of 63 Italian patients with WS was studied by analysing the dosage of antigliadin antibodies (AGA) IgA and antiendomisium antibodies (AEA). In patients with positive AGA and AEA, small bowel biopsy was performed. The prevalence of CD in our WS population was compared with that estimated in a published series of 17 201 Italian students. Seven WS patients were found to be positive for AGA IgA and AEA. Six of them underwent small bowel biopsy, which invariably disclosed villous atrophy consistent with CD. The prevalence of CD in the present series of WS patients was 9.5% (6/63), compared to 0.54% (1/184) in the Italian students (p<0.001).
CONCLUSION: The present results suggest that the prevalence of CD in WS is higher than in the general population and is comparable to that reported in DS and TS. AGA and AEA screening is recommended in patients with WS.
PATHOGENESIS CHARACTERIZATION CHROMOSOMAL ABNROMALITIES Nucleotide Identification of GTF2IRD1, a putative transcription factor within the Williams-Beuren syndrome deletion at 7q11.23.
Franke Y, Peoples RJ, Francke U.
Department of Genetics, Stanford University School of Medicine, Stanford CA, USA.
Cytogenet Cell Genet 1999;86(3-4):296-304 Abstract quote
Williams-Beuren syndrome (WBS) is a microdeletion syndrome caused by haploinsufficiency of genes at 7q11.23.
Here we describe the identification and characterization of a novel gene named GTF2IRD1, for GTF2I-repeat domain 1, within the WBS deletion region. Northern blot analysis revealed ubiquitous expression during development with two transcripts of 3.6 kb and 5.0 kb generated by alternative splicing. GTF2IRD1 encodes a protein of 944 amino acids that contains a region of high similarity to a unique motif with helix-loop-helix forming potential occurring within the transcription factor GTF2I. Analogous to TFII-I, the product of GTF2IRD1 may have the ability to interact with other HLH-proteins and function as a transcription factor or as a negative transcriptional regulator. A recent report of the identification of a muscle-specific transcription factor, MusTRD1, supports this hypothesis (O'Mahoney et al., 1998).
The open reading frame described for MusTRD1 is identical to that of GTF2IRD1; however, the putative MusTRD1-protein is 486 amino acids shorter than the predicted protein encoded by GTF2IRD1. A heterozygous deletion of GTF2IRD1 may contribute to the complex WBS phenotype.
Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD3 genes.
Botta A, Novelli G, Mari A, Novelli A, Sabani M, Korenberg J, Osborne LR, Digilio MC, Giannotti A, Dallapiccola B.
Department of Biopathology and Diagnostic Imaging, Tor Vergata University of Rome, Italy.
J Med Genet 1999 Jun;36(6):478-80 Abstract quote
We present two patients with the full Williams syndrome (WS) phenotype carrying a smaller deletion than typically observed. The deleted region spans from the elastin gene to marker D7S1870.
This observation narrows the minimal region of deletion in WS and suggests that the syntaxin 1A and frizzled genes are not responsible for the major features of this developmental disorder and provides important insight into understanding the genotype-phenotype correlation in WS.
Protein Comparative genomic sequence analysis of the Williams syndrome region (LIMK1-RFC2) of human chromosome 7q11.23.
Martindale DW, Wilson MD, Wang D, Burke RD, Chen X, Duronio V, Koop BF.
Department of Biology, Centre for Environmental Health, P.O. Box 3020, University of Victoria, Victoria, British Columbia, V8W 3N5 Canada.
Mamm Genome 2000 Oct;11(10):890-8 Abstract quote
Williams syndrome (WS) is a complex neurodevelopmental disorder arising from a microdeletion at Chr band 7q11.23, which results in a hemizygous condition for a number of genes.
Within this region we have completely characterized 200 kb containing the genes LIMK1, WBSCR1, and RFC2. Evidence was also found for WBSCR5 in this region, but not the previously proposed genes WSCR2 and WSCR6. The syntenic region in mouse was also sequenced (115 kb) and characterized, and a comparative sequence analysis with a percent identity plot (PIP) easily allowed us to identify coding exons. This genomic region is GC rich (50.1% human, 49.9% mouse) and contains an unusually high abundance of repetitive elements consisting primarily of Alu (45.4%, one of the highest levels identified to date) in human, and the B family of SINES (30.6% of the total sequence) in mouse.
WBSCR1 corresponds to eukaryotic initiation factor 4H, identified in rabbit, and is herein found to be constitutively expressed in both human and mouse, with two RNA and protein products formed (exon 5 is alternatively spliced). The transcription pattern of WBSCR5 was also examined and discussed along with its putative amino acid sequence.
Williams syndrome and related disorders.
Morris CA CA, Mervis CB PhD CB.
Department of Pediatrics, Division of Genetics, Univ. Nevada School of Medicine, Las Vegas, NV 89102
Annu Rev Genomics Hum Genet 2000;1:461-84 Abstract quote
Three clinical conditions displaying phenotypic overlap have been linked to mutation or deletion of the elastin gene at 7q11.23.
Supravalvar aortic stenosis, an autosomal dominant disorder characterized by elastin arteriopathy, is caused by mutation or intragenic deletions of ELN resulting in loss of function. Autosomal dominant cutis laxa, a primarily cutaneous condition, is the result of frameshift mutations at ELN that cause a dominant-negative effect on elastic fiber structure.
Williams syndrome, a neurodevelopmental disorder is due to a 1.5 Mb deletion that includes ELN and at least 15 contiguous genes. The disorder is characterized by dysmorphic facies, mental retardation or learning difficulties, elastin arteriopathy, a unique cognitive profile of relative strength in auditory rote memory and language and extreme weakness in visuospatial constructive cognition, and a typical personality that includes overfriendliness, anxiety, and attention problems.
The understanding of these disorders has progressed from phenotypic description to identification of causative mutations and insight into pathogenetic mechanisms for some aspects of the phenotype.
Deletions at chromosome regions 7q11.23 and 7q36 in a patient with Williams syndrome.
Wouters CH, Meijers-Heijboer HJ, Eussen BJ, van der Heide AA, van Luijk RB, van Drunen E, Beverloo BB, Visscher F, Van Hemel JO.
Department of Clinical Genetics, University Hospital Dijkzigt and Erasmus University, Rotterdam, The Netherlands.
Am J Med Genet 2001 Aug 15;102(3):261-5 Abstract quote
We report on a patient with Williams syndrome and a complex de novo chromosome rearrangement, including microdeletions at 7q11.23 and 7q36 and additional chromosomal material at 7q36.
The nature of this additional material was elucidated by spectral karyotyping and first assigned to chromosome 22. Subsequent fluorescence in situ hybridization (FISH) experiments showed that it consisted of satellite material only. Refinement of the 7q36 breakpoint was performed with several FISH probes, showing a deletion distal to the triphalangeal thumb (TPT) region.
The phenotype of the patient principally results from the microdeletion of the 7q11.23; the small deletion at 7qter and the extra satellite material may not be of clinical significance.
CARDIOVASCULAR Mechanical properties of the common carotid artery in Williams syndrome.
Aggoun Y, Sidi D, Levy BI, Lyonnet S, Kachaner J, Bonnet D.
INSERM 0016 and Service de Cardiologie Pediatrique, Hopital Necker-Enfants Malades, 149 rue de Sevres 75743, Paris Cedex 15, France.
Heart 2000 Sep;84(3):290-3 Abstract quote
OBJECTIVE: To determine whether arterial wall hypertrophy in elastic arteries was associated with alteration in their mechanical properties in young patients with Williams syndrome.
METHODS: Arterial pressure and intima-media thickness, cross sectional compliance, distensibility, circumferential wall stress, and incremental elastic modulus of the common carotid artery were measured non-invasively in 21 Williams patients (mean (SD) age 8.5 (4) years) and 21 children of similar age.
RESULTS: Systolic and diastolic blood pressures were higher in Williams patients (125/66 v 113/60 mm Hg, p < 0.05). The mean (SD) intima-media thickness was increased in Williams patients, at 0.6 (0.07) v 0.5 (0.03) mm (p < 0. 001). Normotensive Williams patients had a lower circumferential wall stress (2.1 (0.5) v 3.0 (0.7) mm Hg, p < 0.01), a higher distensibility (1.1 (0.3) v 0.8 (0.3) mm Hg(-1).10(-2), p < 0.01), similar cross sectional compliance (0.14 (0.04) v 0.15 (0.05) mm(2). mm Hg(-1), p > 0.05), and lower incremental elastic modulus (7.4 (2. 0) v 14.0 (5.0) mm Hg.10(2); p < 0.001).
CONCLUSIONS: The compliance of the large elastic arteries is not modified in Williams syndrome, even though increased intima-media thickness and lower arterial stiffness are consistent features. Therefore systemic hypertension cannot be attributed to impaired compliance of the arterial tree in this condition.
Evaluation of arterial stiffness in children with Williams syndrome: Does it play a role in evolving hypertension?
Salaymeh KJ, Banerjee A.
Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Am Heart J 2001 Sep;142(3):549-55 Abstract quote
BACKGROUND: Pathologic studies and surgical observations of thickened aortic walls have suggested an increase in aortic stiffness in patients with Williams syndrome. However, in vivo objective evaluation of aortic and arterial stiffness in Williams syndrome are lacking. Moreover, systemic hypertension, although prevalent in Williams syndrome, does not have a well-defined mechanism in this syndrome. Therefore, the purpose of this study was to quantitate aortic stiffness and arterial compliance in an objective manner, as well as to determine their roles in development of hypertension, in children with Williams syndrome.
METHODS: We studied 13 patients with Williams syndrome (aged 3-12 years) and 16 age-matched control subjects. Aortic stiffness was calculated from the beta index as follows: beta = (ln[P(s)/P(d)])/ ([D(s) - D(d)]/D(d)), where P(s) and P(d) are systolic and diastolic blood pressures and D(s) and D(d) are systolic and diastolic aortic dimensions, respectively. Arterial compliance (C) was calculated by the area method: C= (A(d) x CO x CL) / (A(t) x [P(es) - P(d)]), where A(t) is the total area and A(d) is the area under the diastolic portion of the arterial pulse tracing, CO is the cardiac output, CL is the cycle length, and P(es) is aortic end-systolic pressure.
RESULTS: In patients with Williams syndrome, the beta index was 2-fold higher than in control patients (9.02 +/- 3.15 vs 4.43 +/- 0.96, P <.005). Moreover, there was a strong positive correlation between the beta index and the systolic blood pressure (r = 0.8 and P <.0001). Compliance was decreased by 42% (0.41 +/- 0.11 vs 0.71 +/- 0.10 mL/mm Hg, P <.05), suggesting decreased arterial compliance.
CONCLUSIONS: Our study indicates that in vivo arterial stiffness is increased in patients with Williams syndrome. We speculate that increased arterial stiffness may be the predisposing cause of systemic hypertension in Williams syndrome.
LABORATORY/RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC Dorsal forebrain anomaly in Williams syndrome.
Galaburda AM, Schmitt JE, Atlas SW, Eliez S, Bellugi U, Reiss AL.
Department of Neurology, Beth Israel-Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA.
Arch Neurol 2001 Nov;58(11):1865-9 Abstract quote
BACKGROUND: Williams syndrome (WMS) is a rare neurogenetic condition with a behavioral phenotype that suggests a dorsal and/or ventral developmental dissociation, with deficits in dorsal but not the ventral hemispheric visual stream. A shortened extent of the dorsal central sulcus has been observed in autopsy specimens.
OBJECTIVE: To compare gross anatomical features between the dorsal and ventral portions of the cerebral hemispheres by examining the dorsal extent of the central sulcus in brain magnetic resonance images from a sample of subjects with WMS and age- and sex-matched control subjects.
SUBJECTS: Twenty-one subjects having clinically and genetically diagnosed WMS (mean +/- SD age, 28.9 +/- 7.9 years) were compared with 21 age- and sex-matched typically developing controls (mean +/- SD age, 28.8 +/- 7.9 years).
DESIGN: High-resolution structural magnetic resonance images were acquired. The extent of the central sulcus was qualitatively assessed via surface projections of the cerebral cortex.
RESULTS: The dorsal central sulcus is less likely to reach the interhemispheric fissure in subjects with WMS than in controls for both left (P< .001, chi(2) = 15.79) and right (P< .001, chi(2) = 12.95) hemispheres. No differences between the groups were found in the ventral extent of the central sulcus.
CONCLUSIONS: Anomalies in the dorsal region in patients with WMS are indicative of early neurodevelopmental problems affecting the development of the dorsal forebrain and are most likely related to the deficits in visuospatial ability and behavioral timing often observed in this condition.
LABORATORY MARKERS Diagnosis of DiGeorge and Williams syndromes using FISH analysis of peripheral blood smears.
Novelli A, Sabani M, Caiola A, Digilio MC, Giannotti A, Mingarelli R, Novelli G, Dallapiccola B.
Department of Biopathology and Diagnostic Imaging, Tor Vergata University, Rome, Italy.
Mol Cell Probes 1999 Aug;13(4):303-7 Abstract quote
We describe the use of a FISH protocol for detecting chromosome microdeletions in peripheral blood smear leukocytes.
This method has the advantage of a smaller sample requirement than classical metaphase chromosome analysis and the potential for analysis of a larger number of chromosome microdeletions using a routine blood smear. A selected series of 10 DiGeorge syndrome (DGS) and 12 Williams-Beuren syndrome (WBS) patients were correctly diagnosed by this method confirming results obtained by molecular cytogenetic metaphases.
These results support effectiveness of interphase FISH analysis on peripheral blood smears as a focused, single-step method for the detection of chromosome microdeletions.
Serum NGF levels in children and adolescents with either Williams syndrome or Down syndrome.
Calamandrei G, Alleva E, Cirulli F, Queyras A, Volterra V, Capirci O, Vicari S, Giannotti A, Turrini P, Aloe L.
Laboratorio di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome, Italy.
Dev Med Child Neurol 2000 Nov;42(11):746-50 Abstract quote
The neurotrophin nerve growth factor (NGF) is a major regulator of peripheral and central nervous system development.
Serum NGF was measured in normally developing control children (n=26) and in individuals affected by congenital syndromes associated with learning disability: either Williams syndrome (WS; n=12) or Down syndrome (DS; n=21).
Participants were assessed at three distinct developmental stages: early childhood (2 to 6 years), childhood (8 to 12 years), and adolescence (14 to 20 years). A sample was taken only once from each individual. Serum NGF levels were markedly higher in participants with WS, than DS and control participants. In addition, different developmental profiles emerged in the three groups: while in normally developing individuals NGF levels were higher in early childhood than later on, children with WS showed constantly elevated NGF levels.
When compared to control participants, those with DS showed lower NGF levels only during early childhood. Neuropsychological assessment confirmed previously reported differences among the three groups in the development of linguistic/cognitive abilities. Some features of individuals with WS, such as hyperacusis and hypertension, could be related to high-circulating NGF levels.
High resolution comparative genomic hybridisation in clinical cytogenetics.
Kirchhoff M, Rose H, Lundsteen C.
Cytogenetic Laboratory, Department of Clinical Genetics, Juliane Marie Centre, University Hospital, Copenhagen, Denmark.
J Med Genet 2001 Nov;38(11):740-4 Abstract quote
High resolution comparative genomic hybridisation (HR-CGH) is a diagnostic tool in our clinical cytogenetics laboratory.
The present survey reports the results of 253 clinical cases in which 47 abnormalities were detected. Among 144 dysmorphic and mentally retarded subjects with a normal conventional karyotype, 15 (10%) had small deletions or duplications, of which 11 were interstitial. In addition, a case of mosaic trisomy 9 was detected. Among 25 dysmorphic and mentally retarded subjects carrying apparently balanced de novo translocations, four had deletions at translocation breakpoints and two had deletions elsewhere in the genome. Seventeen of 19 complex rearrangements were clarified by HR-CGH. A small supernumerary marker chromosome occurring with low frequency and the breakpoint of a mosaic r(18) case could not be clarified. Three of 19 other abnormalities could not be confirmed by HR-CGH.
One was a Williams syndrome deletion and two were DiGeorge syndrome deletions, which were apparently below the resolution of HR-CGH. However, we were able to confirm Angelman and Prader-Willi syndrome deletions, which are about 3-5 Mb.
We conclude that HR-CGH should be used for the evaluation of (1) dysmorphic and mentally retarded subjects where normal karyotyping has failed to show abnormalities, (2) dysmorphic and mentally retarded subjects carrying apparently balanced de novo translocations, (3) apparently balanced de novo translocations detected prenatally, and (4) for clarification of complex structural rearrangements.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL VARIANTS The middle aortic syndrome: an important feature of Williams' syndrome.
Radford DJ, Pohlner PG.
Queensland Centre for Congenital Heart Disease, The Prince Charles Hospital, Brisbane, Australia.
Cardiol Young 2000 Nov;10(6):597-602 Abstract quote
The middle aortic syndrome, with diffuse narrowing of the thoracic and abdominal aorta, was present in 10 of 18 patients with Williams' syndrome (55%).
There were 3 thoracic coarctations, and 2 abdominal coarctations, with gradients greater than 20 mmHg across the zone of narrowing. Seven patients had mild renal arterial stenosis, and 6 had visceral arterial stenoses. Ten were hypertensive. Measured dimensions of the aortic lumen failed to increase with age in 3 males who had serial angiographic studies. One developed mesenteric arterial stenosis, with mild bilateral renal arterial stenoses, between the ages of 9 and 19 years. Aortic intravascular ultrasound performed in 2 patients confirmed abnormally thick vessel walls with small lumens. Diffusely narrowed and thick-walled stiff arteries, lacking elastin, are a feature of Williams' syndrome.
The arteriopathy tends to progress with age, and systemic hypertension is common in teenagers and beyond. The middle aortic syndrome was present in more than half our patients, and does not necessarily reflect a bias because of cardiologic referral.
Aortography with measurement of aortic diameters and delineation of the visceral branches is an important requirement for complete evaluation of patients with Williams' syndrome.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL Multi-level analysis of cortical neuroanatomy in Williams syndrome.
Galaburda AM, Bellugi U.
Beth Israel Deaconess Medical Center, Boston, MA, USA.
J Cogn Neurosci 2000;12 Suppl 1:74-88 Abstract quote
The purpose of a neuroanatomical analysis of Williams Syndrome (WMS) brains is to help bridge the knowledge of the genetics of this disorder with the knowledge on behavior.
Here, we outline findings of cortical neuroanatomy at multiple levels. We describe the gross anatomy with respect to brain shape, cortical folding, and asymmetry. This, as with most neuroanatomical information available in the literature on anatomical-functional correlations, links up best to the behavioral profile. Then, we describe the cytoarchitectonic appearance of the cortex. Further, we report on some histometric results. Finally, we present findings of immunocytochemistry that attempt to link up to the genomic deletion. T
he gross anatomical findings consist mainly of a small brain that shows curtailment in the posterior-parietal and occipital regions. There is also subtle dysmorphism of cortical folding. A consistent finding is a short central sulcus that does not become opercularized in the interhemispheric fissure, bringing attention to a possible developmental anomaly affecting the dorsal half of the hemispheres. There is also lack of asymmetry in the planum temporale.
The cortical cytoarchitecture is relatively normal, with all sampled areas showing features typical of the region from which they are taken. Measurements in area 17 show increased cell size and decreased cell-packing density, which address the issue of possible abnormal connectivity. Immunostaining shows absence of elastin but normal staining for Lim-1 kinase, both of which are products of genes that are part of the deletion. Finally, one serially sectioned brain shows a fair amount of acquired pathology of microvascular origin related most likely to underlying hypertension and heart disease.
SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION Skin elastic fibers in Williams syndrome.
Dridi SM, Ghomrasseni S, Bonnet D, Aggoun Y, Vabres P, Bodemer C, Lyonnet S, de Prost Y, Fraitag S, Pellat B, Sidi D, Godeau G.
Laboratory of Physiopathology of non mineralized tissues, Faculte de Chirurgie Dentaire, Montrouge, France.
Am J Med Genet 1999 Nov 19;87(2):134-8 Abstract quote
The elastin gene is consistently deleted in Williams syndrome and as this protein represents the major component of the elastic fibers of the dermis, we sought to investigate skin elastic fibers in Williams syndrome as a key to unraveling extracellular matrix disorganization in this condition.
Both morphometric parameters analyzed by using automated image analysis and immunofluorescence labeling with monoclonal antibodies against elastin and fibrillin 1 showed a disorganized pre-elastic (oxytalan and elaunin) and mature elastic fibers in the dermis of 10 Williams syndrome patients compared with five healthy children and one patient with isolated supravalvular aortic stenosis.
Skin biopsies in Williams syndrome patients provide a simple mean to elucidate extracellular matrix anomalies. Hopefully, this method could give clues to the understanding of the elastic network anomalies in this condition and even to the consequences of these latter on elasticity and resilience of other tissues such as the arterial tree.
ELECTRON MICROSCOPY Elastin gene deletions in Williams syndrome patients result in altered deposition of elastic fibers in skin and a subclinical dermal phenotype.
Urban Z, Peyrol S, Plauchu H, Zabot MT, Lebwohl M, Schilling K, Green M, Boyd CD, Csiszar K.
Pacific Biomedical Research Center, University of Hawaii, Honolulu 96822, USA.
Pediatr Dermatol 2000 Jan-Feb;17(1):12-20 Abstract quote
Williams syndrome (WS) is a complex developmental disorder with multisystem involvement known to be the result of a microdeletion in the q11.23 region of chromosome 7. This deletion involves several genes, including the elastin gene. Although elastic fibers are important constituents of skin, little is known about the skin phenotype in WS patients.
We have therefore studied the skin of four WS patients in which we've shown the deletion of one copy of the elastin gene. Physical examination and indirect immunofluorescent microscopy of elastin did not detect any major phenotypic or morphologic changes in the skin.
We were able, however, to show subtle textural changes in skin and, by electron microscopy, that the amorphous component of elastic fibers in WS patients was consistently reduced when compared to normal controls.
These findings indicate that deletion of one copy of the elastin gene results in reduced deposition of elastin in dermal elastic fibers, an altered elastic fiber ultrastructure, and a subclinical dermal phenotype in the children and young adult patients analyzed in this study.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS Personality characteristics and behaviour problems in individuals of different ages with Williams syndrome.
Gosch A, Pankau R.
Research Centre for Prevention and Intervention in Childhood and Adolescence, University of Bielefeld, Germany.
Dev Med Child Neurol 1997 Aug;39(8):527-33 Abstract quote
To study personality characteristics and behaviour problems in different age groups more precisely, the parents of 105 children with Williams syndrome (WS) were asked to complete a questionnaire with a list of 25 personality adjectives and 18 behaviour disturbances.
Three age groups-children under 10 years, adolescents between 10 and 20 years, and adults over 20 years of age-were compared. Adults with WS were described as being less lively, determined, active, restless, tearful, quarrelsome, impertinent, and over-friendly in comparison with children with WS. Additionally, adolescents and adults were assessed as being better balanced and more withdrawn than children with WS. Females were found to be less cheerful and happy as well as more tearful and quarrelsome than males, but these results showed only a statistical tendency.
A discriminant analysis was performed to prove whether the three age groups could be discriminated on the basis of personality aspects.
The results showed correct classification to one of the three age groups in 86% of the individuals with WS. The most discriminating adjectives were active, lively, well balanced, withdrawn, being over-friendly, and vigorous. No differences regarding age or sex were found after calculating a composite score of behaviour problems reported in each individual. However, a comparison of single behaviour problems showed a decrease in external aggressive behaviours and greater depressive symptoms with increasing age.
TREATMENT Supportive Treatment of children with Williams syndrome with methylphenidate.
Bawden HN, MacDonald GW, Shea S.
Department of Psychology, IWK-Grace Health Centre, Halifax, NS, Canada.
J Child Neurol 1997 Jun;12(4):248-52 Abstract quote
Children with Williams syndrome frequently present with symptoms of attention deficit hyperactivity disorder (ADHD), but there is little information that stimulant medication is useful in this population.
A series of double-blind, placebo-controlled case studies was used to evaluate the cognitive and behavioral effects of methylphenidate on four children with Williams syndrome. Teachers and mothers completed behavioral rating scales and cognitive tests of attention, learning and memory, and academic productivity and accuracy in mathematics in each medication condition. Two of the children responded favorably in terms of decreased impulsivity, decreased irritability, and lower activity level as well as improved ability to pay attention.
Methylphenidate is a useful adjunct in the treatment of some children with Williams syndrome.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Weedon D. Weedon's Skin Pathology. Churchill Livingstone. 1997.
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
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