Sigmoid diverticulitis in patients with Williams-Beuren syndrome: relatively high prevalence and high complication rate in young adults with the syndrome.

In a retrospective survey of 128 adults with Williams-Beuren syndrome (age range 18-62 years) sigmoid diverticulitis was reported in 10 patients (2 f, 8 m). The diagnosis of diverticulitis had been made between the ages of 17.1 and 39.6 years. An additional four patients (age range 23.5-32.2 years) had presented with sigmoid diverticulosis. In eight patients the course of the disease was complicated, some of them having to undergo multiple surgery. Conservative therapy was successful in only one female and one male patient with diverticulitis. Thus, we conclude that there is an increased prevalence of sigmoid diverticulitis in adult patients with Williams-Beuren syndrome (8% vs. 2% in the normal population in the age group below 40 years).

[Hearing screening with automatic evaluation of TEOAE and a new method of automatic evaluation of early auditory evoked potentials. Optimization and field trial]. / Hörscreening mit automatisch bewerteten TEOAE und einem neuen Verfahren automatisch bewerteter FAEP. Optimierung und Feldversuch.

BACKGROUND AND OBJECTIVE: To make a rational decision as to which screening test might be adequate as a universal newborn hearing screening, different methods have to be tested under "real-life" conditions. In addition, a good reference is required as "golden standard." PATIENTS/METHODS: In the study presented here, an ABR with a novel algorithm for threshold-estimation was optimized and compared to TEOAE (Echoscreen) and DPOAE (GSI 60) in a three-step protocol using a standard click-evoked ABR (Evoselect) as reference of sensitivity and specificity. RESULTS: 26 ears were found to be hearing-impaired. All of them were also detected by each of the screening method (sensitivity 100%). Specificity in the final "step 2" of the study was around 87.7/92.3% for Echoscreen, 82.4/84.4% for DPOAE and 82.4/89.1 for Evoflash (left/right, respectively). Differences were not at all significant (X2-test, p > > 0.05). In summary, results were somewhat inferior to those found by other authors, probably due to more difficult conditions in the "real-life" setting. CONCLUSIONS: A higher rate of false-alarm shows that a two-step screening is necessary. Therefore, increased resources for diagnostic procedures are required.

Familial Williams-Beuren syndrome showing varying clinical expression.

Williams-Beuren syndrome (WBS) is a contiguous gene syndrome that occurs mainly sporadically, with an estimated frequency of 1:13,700 to 1:25,000 [Grimm and Wesselhoeft, 1980; Martin et al., 1984; Udwin, 1990]. The cases of monozygotic twins concordant for WBS and dizygotic twins discordant for the syndrome have been reported. In addition, a few familial cases have been described since 1993. The clinical diagnosis has been supported by molecular genetic findings in only two patients, however. We herein report on two families in which the WBS was inherited in girls from their mothers. All four patients showed the typical hemizygous deletion at 7q11.23 [46,XX, ish,del(7)(q11.23q11.23) (ELN/LIMK1/D7S-613x1, D7S486/D7S522x2)], but the clinical picture was strikingly variable within and between families.

Anomalies of the abdominal aorta in Williams-Beuren syndrome--another cause of arterial hypertension.

UNLABELLED: Vascular disease in Williams-Beuren syndrome is based on an elastin arteriopathy which may cause stenoses in small and great vessels. This study presents the pattern of stenotic lesions of the abdominal aorta and the incidence of arterial hypertension. From 112 patients with Williams-Beuren syndrome followed since 1975, 25 patients were studied by aortography. The diameter of the thoracic aorta and the change in diameter to the iliac bifurcation were compared with normal data. Renal artery stenosis was suspected when the proximal vessel diameter was less than 50% of the distal diameter. Of the 25 patients, 20 had vascular stenosis of whom 19 patients were affected by segmental narrowing either of the thoracic aorta (n=9) or the abdominal aorta (n = 7) or both (n = 3). Hypoplasia of the abdominal aorta was characterised by the smallest diameters at the renal artery level and an increased diameter of the infrarenal abdominal aorta. A total of 11 patients had renal arterial stenosis, associated with narrowing of other aortic segments in 10 cases. Only one patient had a solitary stenosis of the renal artery. Arterial hypertension was diagnosed in 17 patients, 2 of them had no vascular lesions; in the remaining 15 patients stenosis was present in more than one segment (aorta 6, renal artery stenosis 1, both 8). CONCLUSION: Narrowing of the abdominal aorta in patients with Williams-Beuren syndrome is a frequent morphological manifestation of the arteriopathy. Isolated renal arterial stenosis was rare, since it was more frequently combined with a narrowed aorta. Hypertension is a common symptom in the affected group and must be regarded as a manifestation of generalised arteriopathy rather than renal hypoperfusion.

Pediatric reference values of estradiol, testosterone, lutropin, follitropin and prolactin.

Reference ranges for lutropin, follitropin, estradiol, testosterone, and prolactin were established by electrochemiluminescence immunoassays (Elecsys 2010, Roche Diagnostics) in 299 children of eight different age groups. The estradiol concentrations did not differ between the genders but dropped significantly in the first few months of life. The testosterone concentrations were higher in male than in female children, whereas the concentrations of follitropin were higher in female than in male children. The concentrations of lutropin were higher in male children (months 1-12) and higher in pubertal girls (years 13-20) in comparison to the corresponding age and gender.

Adult patients with Prader-Willi syndrome: clinical characteristics, life circumstances and growth hormone secretion.

Prader-Willi syndrome is characterized by a typical clinical phenotype and by a complex genetic basis that includes large deletions, uniparental disomy and imprinting mutations of chromosome region 15q11-q13. This report delineates the clinical characteristics, morbidity and growth hormone secretory status of 19 adults with Prader-Willi syndrome. The patients were 18-34 years of age. Morbidity included marked obesity with body mass index in excess of 30 kg/m2 (grade 1-3 according to WHO), metabolic diseases, sleep apnoea and lipolymphoedema. Severe growth hormone deficiency (GHD) was seen in 38% of the patients, and levels of insulin-like growth factor I were decreased in 87%. Thus, GHD is seen, not only in children with Prader-Willi syndrome, but also in adults with the syndrome.

Longitudinal evaluation of growth, puberty, and bone maturation in children with Williams syndrome.

OBJECTIVES: To establish syndrome-specific growth curves and growth rate (GR) curves for Williams syndrome (WS) and define the pattern of bone maturation and pubertal development. METHODS: In a prospective longitudinal study between 1990 and 1997, the growth data of 244 children with WS were collected: 295 values for GR were calculated for 74 girls and 331 values for 89 boys. RESULTS: Mean GR of children with WS was below normal by 1 to 2 cm/y in the first few years of life. One group of girls (n = 20) experienced an early pubertal growth spurt at age 9 years (maximal GR, 7.8 +/- 2.1 cm/y; menarcheal age, 10.4 +/- 1.4 years). A second group (n = 5) showed the growth spurt at age 11 years (7.5 +/- 1.1 cm/y; menarcheal age, 12.6 +/- 1.3 years). In boys, peak height velocity (8.7 +/- 2.3 cm/y) occurred at age 11 to 12 years. Bone age was delayed in both sexes during childhood and accelerated markedly during puberty. Final height was 152.4 +/- 5.7 cm in girls (n = 38) and 165.2 +/- 10. 9 cm in boys (n = 43). CONCLUSIONS: The syndrome-specific GR curves for WS showed a premature and abbreviated pubertal growth spurt in both sexes. This growth spurt was directly related to bone age acceleration during puberty. The data from this longitudinal study provide an overview of both the dynamics of growth and its course in children with WS.

Personality characteristics and behaviour problems in individuals of different ages with Williams syndrome.

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.

[Arterial hypertension and blood pressure profile in patients with Williams-Beuren syndrome]. / Arterielle Hypertension und Blutdruckprofil bei Patienten mit Williams-Beuren-Syndrom.

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.

Incidence and spectrum of renal abnormalities in Williams-Beuren syndrome.

Kidneys and urinary tract were examined systematically by ultrasonography in 130 patients with Williams-Beuren syndrome (59 females, median age 5.5 years; 71 males, median age 6.4 years). In addition, serum creatinine was determined and an analysis was performed. Creatinine clearance was available in 79 patients. Renal angiographic examinations were done in 18 patients, 8 of whom had renal artery narrowing (44%). The incidence of renal anomalies in Williams-Beuren syndrome was 17.7% vs. around 1.5% in the normal population (P < 0.0003). The spectrum of these anomalies ranged from minor anomalies such as bladder diverticula to more severe malformations such as renal aplasia or hypoplasia (in 5 of 130 patients). In nine patients a duplicated kidney was found. A decreased creatinine clearance (two patients), recurrent symptomatic urinary tract infections (four patients), and hypertension were uncommon. Nephrocalcinosis was not found in our patients. Our data demonstrate that the risk of a structural abnormality of the kidneys and the urinary tract is increased 12- to 36-fold in Williams-Beuren syndrome compared to the normal population. Ultrasound screening of the renal system should be part of the first evaluation of WBS patients.

Longitudinal study of the cognitive development in children with Williams-Beuren syndrome.

Crisco [1990: Clin Res 38:536A] reported stability of IQs in a group of 14 children with Williams-Beuren syndrome (WBS) over a 5-year period and concluded that they display a development rate similar to normal children. The aim of our study was to examine the stability of the development of nonverbal reasoning abilities over a period of 2 years using two methods. We studied 18 children with WBS (9 girls, 9 boys) with a mean age of 6.6 years (range: 4.4-10.6 yr) at year one (T1), and approximately two years later (T2) at the average age of 8.6 years (range: 5.11-12.7 yr). The Columbia Mental Maturity Scale (CMM) and the Draw A Person Test were administered. The results show that the IQs resulting from the Draw A Person Test were stable over the 2-year period (T1: mean IQ = 63.5, T2: mean IQ = 65, t = 0.63), and display a significant correlation between the two methods (r = 0.547, P = 0.01). Furthermore, the correlation between the two tests (CMM and Draw A Person Test) at the second assessment is high and significant (r = 0.56, P = 0.01). The mean IQs at T2 can be classified as mild mental retardation. A notable result is the significant decrease of the IQs according to the CMM (T1: mean IQ = 77, T2: mean IQ = 68, t = 2.69, P = 0.01). These results suggest that the developmental outcome of children with WBS varies in specific areas of cognitive function over a 2-year period.

The spectrum of ocular features in the Williams-Beuren syndrome.

One hundred and fifty-two patients with the Williams-Beuren syndrome were examined to assess the frequency and severity of ophthalmological features associated with the disorder. Eighty-two (54%) had strabismus, all but three, esotropia. One hundred and seventeen (77%) patients had blue irides, 10 (7%) green, and 25 (16%) brown. One hundred and twelve (74%) showed a typical so-called stellate iris pattern of the anterior stroma. Whitish anomalies were also detectable in brown irides. Two 9-year-old patients and one 46-year-old patient had initial cataract. Of all the patients with funduscopy, 22% had retinal vascular tortuosity. One patient had suspected Rieger syndrome. Two patients had ptosis, one with a Marcus-Gunn phenomenon. No ocular manifestation of hypercalcaemia was noted.

Social-emotional and behavioral adjustment in children with Williams-Beuren syndrome.

In children with Williams-Beuren syndrome (WBS), disturbed behaviors (neurotic, antisocial, and hyperactive) [Arnold et al., 1985: Dev Med Child Neurol 27:49-59; Udwin et al., 1987: J Child Psychol Psychiat 28:297-309] have been described. To study the behavior disturbances and social-emotional adjustment in children with WBS, a group of N = 19 patients was compared with a control group, matched for age, gender, and nonverbal reasoning abilities. Parents were asked to assess the children's behavior in terms of a list of 20 items of the Child Behavior Checklist (CBCL) [Achenbach and Edelbrock, 1983: Manual for the Child Behavior Checklist] and the Vineland Social Maturity Scale (VSMS) [Lüer et al., 1972: Kurzform der Vineland Social Maturity Scale]. As compared with the control group, children with WBS differ significantly in their social behavior towards strangers. They exhibit no reserve or distancing behavior and would, for instance, follow a stranger without hesitation. They are described as showing a hypersensitivity to sounds that is more pronounced than in the control group. Finally, they are found to be significantly less well-adjusted socially than the control individuals.

Dermatoglyphic peculiarities in patients with Williams-Beuren syndrome.

The dermatoglyphic patterns of fingertips and palms of 115 patients with Williams-Beuren syndrome (WBS) were analysed and compared with the data from 199 control individuals from Germany. The following combination of dermatoglyphic patterns appears to be characteristic to WBS: an excess of whorls on all fingertips; high termination values of the main lines D, B, and A; frequent absence of C triradius (C0); high frequencies of ulnar loops on the hypothenar and distal loops on the 2nd, 3rd, and 4th interdigital areas, of distal axial triradii t", and of abnormal palmar creases such as simian crease and Sydney lines. The combination of fingertip and palmar patterns expressed by a "Log.Score-Index," provides a high degree of discrimination between the WBS patients (92%) and the control group (88%). A "phantom picture" for WBS was constructed, which can be used for its diagnosis.