(Genetic diagnosis of Williams syndrome) A Williams-szindroma genetikai diagnozisa. Urban Z; Kiss E; Kadar K; Szabolcs J; Csiszar K; Boyd DC; Fekete G Semmelweis Orvostudomanyi Egyetem, II. Gyermekklinika Budapest. Orv Hetil (HUNGARY) Jul 6 1997, 138 (27) p1749-52, ISSN 0030-6002 Languages: HUNGARIAN Summary Languages: ENGLISH Document type: JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES English Abstract
Williams syndrome is a complex developmental disorder. The major cardiovascular component of Williams syndrome is supravalvular aortic stenosis, a progressive disease that may need surgical repair. Williams syndrome is associated with heterozygous microdeletion in the chromosomal region 7q11.23 encompassing the elastin gene. We have identified a new, highly informative tetranucleotide repeat polymorphism within the human elastin gene. This marker together with other, previously described elastin gene markers was used to show deletion of the elastin gene in nine sporadic Williams syndrome patients from Hungary. Application of polymorphisms within and flanking the elastin gene on chromosome 7 provides a fast, polymerase chain reaction based method for mutational analysis of Williams syndrome patients. (27 Refs.)
Record 2
Elastin: genomic structure and point mutations in patients with supravalvular aortic stenosis. Tassabehji M; Metcalfe K; Donnai D; Hurst J; Reardon W; Burch M; Read AP Department of Medical Genetics, St Mary's Hospital, Manchester, UK. [email protected] Hum Mol Genet (ENGLAND) Jul 1997, 6 (7) p1029-36, ISSN 0964-6906 Languages: ENGLISH Document type: JOURNAL ARTICLE
We describe the complete exon-intron structure of the human elastin (ELN) gene located at chromosome 7q11.23. There are 34 exons occupying approximately 47 kb of genomic DNA. All exons are in-frame, allowing exon skipping without disrupting the reading frame. Microsatellites are located in introns 17 and 18. Deletions of all or large parts of the ELN gene have been previously reported in two patients with supravalvular aortic stenosis (SVAS), and SVAS is also a frequent feature of Williams syndrome, where patients are hemizygous for ELN. We list primer pairs for amplifying each exon, with flanking intron, from genomic DNA to allow detection of point mutations in the ELN gene. We show that some patients with isolated SVAS have point mutations that are predicted to lead to premature chain termination. Knowledge of the genomic structure will allow more extensive mutation screening in genomic DNA of patients with SVAS and other conditions.
Record 3
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 (UNITED STATES) Jun 1997, 12 (4) p248-52, ISSN 0883-0738 Languages: ENGLISH Document type: CLINICAL TRIAL; JOURNAL ARTICLE
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.
Record 4
Hyperacusis in Williams syndrome: a sample survey study. Van Borsel J; Curfs LM; Fryns JP Centrum voor Gehoor-en Spraakrevalidatie, UZ Gent, Belgium. Genet Couns (SWITZERLAND) 1997, 8 (2) p121-6, ISSN 1015-8146 Languages: ENGLISH Document type: JOURNAL ARTICLE
Williams syndrome is a true multiple congenital anomalies mental retardation syndrome affecting the vascular, connective tissue and the central nervous system. Affected individuals have a distinctive neuropsychological profile characterized by extremely poor visuospatial skills but relatively preserved verbal skills. A very striking characteristic is the hyperacusis or over-sensitivity to particular sounds. Klein et al. (4) found high rates (95%) of auditory over-sensitivity in a sample of Williams patients. The cause and mechanisms of auditory-over-sensitivity in Williams syndrome remain unclear. Some association has been suggested between hyperacusis and the occurrence of otitis media and also between hyperacusis and hyperactivity. The present study reports the results of an investigation into the occurrence of hyperacusis, otitis media and hyperactivity in a large group (N = 82) of Dutch speaking subjects with Williams syndrome from Belgium and The Netherlands. Prevalence and characteristics of hyperacusis and co-occurrence with otitis media and hyperactivity will be discussed and some management strategies are offered.
Record 5
(Arterial hypertension and blood pressure profile in patients with Williams-Beuren syndrome) Arterielle Hypertension und Blutdruckprofil bei Patienten mit Williams-Beuren-Syndrom. Wessel A; Motz R; Pankau R; Bursch JH Klinik fur Padiatrische Kardiologie, Georg-August-Universitat, Gottingen. Z Kardiol (GERMANY) Apr 1997, 86 (4) p251-7, ISSN 0300-5860 Languages: GERMAN Summary Languages: ENGLISH Document type: JOURNAL ARTICLE English Abstract
The prevalence of hypertension and the diurnal blood pressure pattern were investigated in patients with Williams-Beuren syndrome (WBS) by blood pressure measurements in 142 children, adolescents, and young adults (female n = 62, male n = 80; median age 6.5 years (0.1-34.3 years)) and evaluation of ambulatory blood pressure data from 45 patients (female n = 21, male n = 24; median age 7.8 years (1-23.8 years)). Measurements revealed systolic hypertension in 46.5% of 142 patients, diastolic hypertension occurred in 36.6% (i.e. actual pressure > 95 percentile). According to the ambulatory data 42.2% of 45 patients had hypertension (mean arterial pressure > normal + 2SD). The nocturnal decline of the blood pressure was normal in hypertensive patients but reduced in normotensives (p < 0.01 vs normals). Males were more often hypertensive than females (46% vs 38%). Hypertensives had a higher body mass index than normotensives (19.5 vs 16.6 kg/m2, p < 0.05). In normo- and hypertensive WBS patients mean heart rates were elevated during day- and nighttime (p < 0.02 vs normals) the latter due to a reduced nocturnal decline. The prevalence of hypertension in WBS patients amounts to about 40%, thus being four- to eight-fold in comparison to healthy young adults or children. The diurnal blood pressure pattern and the elevated heart rates indicate that an increased arterial stiffness due to the vascular disease in the WBS and augmented sympathetic activity might play a role in the genesis of hypertension. Thus, effective antihypertensive treatment is likely to become difficult. From our experience beta-blocking agents are often successful in hypertensive WBS patients.
Record 6
Williams syndrome as a model of genetically determined right-hemisphere dominance. Bogdanov NN; Solonichenko VG Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Neurosci Behav Physiol (UNITED STATES) May-Jun 1997, 27 (3) p264-7, ISSN 0097-0549 Languages: ENGLISH Document type: CLINICAL TRIAL; JOURNAL ARTICLE
Studies were carried out on the dermatoglyphics (skin ridge marks) on the hands of children with Williams syndrome; this is an inherited disease with cardiovascular pathology and a characteristic facial phenotype ("elf" facies), along with specific mental and cognitive disturbances. The results suggest a characteristic dermatoglyphic type with the presence of complex whorls on the fingers and a clear predominance of marks of greater complexity on the left hand; this is a very rare trait in normal people and in those with other inherited nervous system disorders. The features of the dermatoglyphic pattern serve as a characteristic marker of a genetically determined state of the human central nervous system, and suggests directions for neurophysiological studies of children with Williams syndrome as a unique model for analysis of higher nervous function in humans.
Record 7
Fluorescent in situ hybridisation (FISH) for hemizygous deletion at the elastin locus in patients with isolated supravalvular aortic stenosis. Fryssira H; Palmer R; Hallidie-Smith KA; Taylor J; Donnai D; Reardon W Mothercare Unit of Clinical Genetics and Fetal Medicine, Institute of Child Health, London, UK. J Med Genet (ENGLAND) Apr 1997, 34 (4) p306-8, ISSN 0022-2593 Languages: ENGLISH Document type: JOURNAL ARTICLE
Both Williams syndrome and isolated supravalvular aortic stenosis (SVAS) are caused by mutations at the elastin locus. Deletion demonstrable by FISH is the hallmark of Williams syndrome, whereas the mutations reported so far in SVAS have been more subtle. FISH positive elastin hemizygosity has not been reported in isolated SVAS. This report records our experience of FISH for elastin deletion in isolated SVAS and specifically reports a patient with non-Williams related SVAS, positive for the elastin deletion by FISH.
Record 8
(Familial supravalvular aortic stenosis. Investigation in a family and review of the literature) Stenose aortique supravalvulaire familiale. Observation d'une famille et revue de la litterature. Burnel P; Marcon F; Lucron H; Bosser G; Gilgenkrantz S; Jonveaux P; Chery M; Worms AM Service de cardiologie infantile, hopital d'Enfants, Vandoeuvre-les-Nancy. Arch Mal Coeur Vaiss (FRANCE) May 1997, 90 (5) p719-24, ISSN 0003-9683 Languages: FRENCH Summary Languages: ENGLISH Document type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL English Abstract Familial supravalvular aortic stenosis is a rare autosomal dominant condition. It may be distinguished from the Williams-Beuren syndrome by the absence of the characteristic dysmorphic appearances and of mental retardation. The case of a 9-year-old girl with a severe surgical stenosis led to the diagnosis of the same malformation in the mother and two brothers. This family adds to the 121 cases reported in the literature describing the main features of SVAS. Molecular biological advances have shown that familial SVAS and the Williams syndrome are due to mutation of the elastin gene located at 7q11-23. In the Williams syndrome the allele of this gene is completely absent and there is also probably deletion of contiguous genes, which explains involvement of cognitive function. In SVAS, the genetic lesion, mutation or microdeletion is more limited, explaining the usually isolated aortic malformation. Other studies are necessary to confirm these results. (12 Refs.)
Record 9
Photoanthropometric study of craniofacial traits in individuals with Williams syndrome. Hovis CL; Butler MG Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37230, USA. Clin Genet (DENMARK) Jun 1997, 51 (6) p379-87, ISSN 0009-9163 Languages: ENGLISH Document type: JOURNAL ARTICLE
A photoanthropometric method, which enables an objective description of facial structures, was used to better delineate the craniofacial characteristics of 29 individuals with Williams syndrome (WS; 18 males and 11 females) between the ages of 0 to 10 years, with an average age of 4.0 years. Facial parameters were measured from strict frontal and profile photographic 35-mm slides and compared with other facial measurements from the same face (e.g., palpebral fissure width to bizygomatic diameter). Sixteen photoanthropometric craniofacial indices were developed from 20 measurements (3 from the frontal face, 2 from the eye region, 3 from the nose region, 2 from the mouth region, 4 from the profile face, and 6 from the ear region). Based on our measurements of 29 Williams syndrome individuals, two parameters (e.g. nose length to midface height and palpebral fissure width to bizygomatic diameter) were outside the normal range when compared with photoanthropometric index standards for age established by Stengel-Rutkowski et al. from white control children. Overall, our data supported a high midface height, broad palpebral fissure width, broad interalar distance, short length of back of nose, prominent ears with long narrow conchae, increased chin height, increased inclination of the ears and a narrow bizygomatic diameter in WS patients. These craniofacial parameters (many not previously evaluated in WS patients) may become useful for early detection, and aid in the diagnosis and study of the development of the characteristic face in Williams syndrome subjects.
Record 10
Phosphoserine phosphatase deficiency in a patient with Williams syndrome. Jaeken J; Detheux M; Fryns JP; Collet JF; Alliet P; Van Schaftingen E Department of Paediatrica, University Hospital Gasthuisberg, University of Leuven, Belgium. J Med Genet (ENGLAND) Jul 1997, 34 (7) p594-6, ISSN 0022-2593 Languages: ENGLISH Document type: JOURNAL ARTICLE
Decreased serine levels were found in plasma and cerebrospinal fluid (CSF) of a boy with pre- and postnatal growth retardation, moderate psychomotor retardation, and facial dysmorphism suggestive of Williams syndrome. Fluorescence in situ hybridisation with an elastin gene probe indicated the presence of a submicroscopic 7q11.23 deletion, confirming this diagnosis. Further investigation showed that the phosphoserine phosphatase (EC 3.1.3.3.) activity in lymphoblasts and fibroblasts amounted to about 25% of normal values. Oral serine normalised the plasma and CSF levels of this amino acid and seemed to have some clinical effect. These data suggest that the elastin gene and the phosphoserine phosphatase gene might be closely linked. This seems to be the first report of phosphoserine phosphatase deficiency.
Record 11
Type IV renal tubular acidosis and uric acid nephrolithiasis in William's syndrome--an unusual mode of renal involvement. De Ferrari ME; Colussi G; Brunati C; Rombola G; Civati G Division of Nephrology and Dialysis, Niguarda-Ca' Granda Hospital, Milan, Italy. Nephrol Dial Transplant (ENGLAND) Jul 1997, 12 (7) p1484-6, ISSN 0931-0509 Languages: ENGLISH Document type: JOURNAL ARTICLE
Record 12
Infantile spasms in two children with Williams syndrome. Tsao CY; Westman JA Department of Pediatrics, The Ohio State University, Columbus, USA. Am J Med Genet (UNITED STATES) Jul 11 1997, 71 (1) p54-6, ISSN 0148-7299 Languages: ENGLISH Document type: JOURNAL ARTICLE
We describe two children with Williams syndrome and infantile spasms. The diagnosis of Williams syndrome was confirmed by documentation of a deletion of the elastin gene/Williams syndrome region at 7q11.23. The diagnosis of infantile spasms was confirmed through the presence of interictal hypsarrhythmia. This represents one of the first reports of infantile spasms in the Williams syndrome.
Record 13
(Surgical treatment of diffuse supravalvular aortic stenosis with
Williams syndrome)
Sudoh Y; Takahara Y; Sunazawa T
Division of Cardiovascular Surgery, Funabashi Municipal Hospital, Chiba,
Japan.
Nippon Kyobu Geka Gakkai Zasshi (JAPAN) May 1997, 45 (5) p764-8,
ISSN 0369-4739
Languages: JAPANESE Summary Languages: ENGLISH
Document type: JOURNAL ARTICLE English Abstract
A five-year-old boy was admitted to our hospital because of a cardiac
murmur and an abnormal electrocardiogram. He had a distinct pattern of
facial features and mild mental and developmental retardation. An aortogram
revealed that the aorta was hypoplastic from just above the Valsalva
sinuses to the aortic arch. Moreover, the basal portions of the arch
vessels were also hypoplastic. A diagnosis of diffuse supravalvular aortic
stenosis was made. The pressure gradient between the left ventricle and the
descending aorta was 74 mmHg on catheter examination. Surgical therapy was
therefore indicated. The hypoplastic lesions of the aorta and arch vessels
were enlarged with a Dacron patch under cardiopulmonary bypass and deep
hypothermic circulatory arrest. The postoperative course was uneventful.
The pressure gradient decreased to 7 mmHg on catheter examination. This
type of supravalvular aortic stenosis is quite rare. Further follow-up is
required to evaluate long-term outcome.
Record 14
A specific deficit of dorsal stream function in Williams' syndrome.
Atkinson J; King J; Braddick O; Nokes L; Anker S; Braddick F
Department of Psychology, University College, London, UK.
Neuroreport (ENGLAND) May 27 1997, 8 (8) p1919-22, ISSN 0959-4965
Languages: ENGLISH
Document type: CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED
TRIAL
Williams' syndrome (WS) is a rare, genetically based disorder of
cognitive development. Affected individuals show a severe deficit of
spatial cognition but a relative sparing of language and face recognition.
To examine the possible neural basis of the spatial deficit, we tested a
group of WS children, aged 4-14 years, on two measures specific to dorsal
cortical stream function: global motion coherence thresholds, in comparison
with an analogous form-coherence test, and visuo-manual accuracy in posting
a card through a slot, compared with matching the slot orientation.
Deficits in these tasks provide the first evidence of specific involvement
in WS of the dorsal stream, the cortical system believed to encode
information about spatial relationships and the visual control of action.
Record 15
Hemizygous deletion of the syntaxin 1A gene in individuals with Williams syndrome (letter) Osborne LR; Soder S; Shi XM; Pober B; Costa T; Scherer SW; Tsui LC Am J Hum Genet (UNITED STATES) Aug 1997, 61 (2) p449-52, ISSN 0002-9297 Languages: ENGLISH Document type: LETTER
Record 16Behavioral and emotional disturbance in individuals with Williams syndrome. Einfeld SL; Tonge BJ; Florio T University of New South Wales. Am J Ment Retard (UNITED STATES) Jul 1997, 102 (1) p45-53, ISSN 0895-8017 Languages: ENGLISH Document type: JOURNAL ARTICLE
Behavioral and emotional disturbance was assessed in 70 children and adolescents with Williams syndrome. They were compared with an epidemiological control population, which was statistically controlled for age, gender, and level of mental retardation. Those with Williams syndrome were more likely to be diagnosed as suffering psychiatric disorder. The disorder was characterized by anxiety, hyperactivity, preoccupations, and inappropriate interpersonal relating. Significantly increased rates of other individual symptoms were also found, including sleep disturbance and hyperacusis. These results, considered with earlier findings, suggest that there is a valid behavior phenotype of Williams syndrome. This is frequently associated with sufficient impairment to consider inclusion of the behavior phenotype in future official taxonomies of mental disorders.
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