Armin Wessel

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.

Statural growth in Williams-Beuren syndrome

The spontaneous growth of 165 patients (75 girls and 90 boys) with Williams-Beuren syndrome was analysed in a mixed longitudinal and cross-sectional manner. Mean (±1 SD) length at birth was 48.2±2.6 cm in girls (n=52) and 49.0±3.0 cm in boys (n=65). Intrauterine growth retardation (length below −2 SD of the normal population) was present in 35% of the girls and 22% of the boys. Poor growth was noted during the first 2 years of life. Until age 9 years in girls and 11 years in boys, mean growth followed the 3rd percentile. A pubertal growth spurt with normal growth rate was seen at age 10 years in girls and 13 years in boys, i.e. 1 to 2 years earlier than normal. Menarche also occurred earlier than normal at a mean age of 11.6±1.5 years (n=28). Mean adult height was 153.9±6.9 cm in girls (n=17) and 168.2±6.9 cm in boys (n=27), approximately corresponding to the 3rd percentile in both sexes and correlating with the genetic height potential (target height). The mean deficit of adult height compared to target height was 10.2 cm in girls and 9.1 cm in boys. Skeletal development progressed at an approximately normal rate in both sexes.

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.

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.

Propranolol treatment of congestive heart failure in infants with congenital heart disease: The CHF-PRO-INFANT Trial

AIM Infants with congenital heart disease and left-to-right shunts may develop significant clinical symptoms of congestive heart failure in spite of therapy with digoxin and diuretics. We investigated the effects of beta-blockade in infants with severe heart failure. METHODS AND RESULTS We performed a prospective, randomized, open monocenter trial in infants treated with digoxin and diuretics (n=10) in comparison to 10 infants receiving additional beta-blocker therapy. After 17 days on average beta-blocker treated infants (propranolol:1,6 mg/kg/day) improved significantly with respect to Ross heart failure score (3.3+/-2.3 vs. 8.3+/-1.9, P=0.002), lower renin levels (338+/-236 vs. 704+/-490 microU/l, P=0.008) and lower mean heart rates in Holter ECG (118+/-10 vs. 142+/-11 beats/min, P<0.001). While digoxin and diuretic treated infants had unchanged mean heart rate (149+/-8 vs. 148+/-10 beats/min), less decrease of symptoms (Ross Score: 8.5+/-1.7 vs. 6.8+/-2.3, P=0.02) but a significant increase of renin levels (139+/-102 vs. 938+/-607 microU/l, P=0.001). CONCLUSION Additional propranolol treatment but not digoxin and diuretics alone can effectively reduce clinical symptoms of heart failure in infants with congenital heart disease, who suffer from increased neurohormonal activation.

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.

Activity of the renin-angiotensin-aldosterone and sympathetic nervous system and their relation to hemodynamic and clinical abnormalities in infants with left-to-right shunts

We studied neurohormonal, clinical and invasively measured hemodynamic data of 47 infants with left-to-right shunts and varying degrees of congestive failure. When referred to a clinical heart failure score, plasma renin activities (r=0.71) and norepinephrine levels (r=0.43) are significantly increased. Arterial hypotension seems to be the hemodynamic trigger of renin release (r=-0.72), but not decreased systemic cardiac index (r=-0.43), the magnitude of the left-to-right shunt (r=0.33) or a reduced ejection fraction (r=0.12). These data indicate neurohormonal activation in infants with left-to-right shunts with preserved myocardial function is similar to the activation in adults with heart failure secondary to myocardial pump failure. These findings have to be considered for optimal medical treatment of these infants with angiotensin-converting enzyme inhibitors or beta-blockers.

Effectiveness of low dose Captopril versus Propranolol therapy in infants with severe congestive failure due to left-to-right shunts

UNLABELLED To evaluate the therapeutical effects of the angiotensin converting enzyme inhibitor Captopril to the beta-blocker Propranolol in infants with congestive failure due to pulmonary overcirculation, we retrospectively analysed clinical, neurohormonal and hemodynamic data in 22 infants, 11 of whom were treated with Captopril (Group 1), 11 with Propranolol (Group 2). Age, weight, number of palliative operations, plasma renin activities and pulmonary to systemic flow ratios (3.5 vs. 3.5) were not significantly different prior to Captopril or Propranolol therapy. If treatment with digoxin and diuretics did not succeed, the infants were additionally treated with Captopril (1 mg/kg) for a mean of 7.4 months, or with 1.9 mg/kg Propranolol for 9.2 months. RESULTS 1 mg/kg Captopril did not effectively suppress angiotensin converting enzyme in the steady state at trough level (92+/-52 vs. 87+/-50 nmol/min/ml). In the Propranolol group, the clinical heart failure score (2.6+/-1.5 vs. 7. 4+/-2.5) and plasma renin activities (14+/-10 vs. 101+/-70 ng/ml/h) were significantly lower, compared to the Captopril group. Length of hospital stay (23+/-9 vs. 52+/-24 days) was lower and weight gain (126+/-38 vs. 86+/-84 g/week) was higher within 3 months after starting Propranolol therapy. Significantly lower left atrial pressures (6.2+/-2.2 vs. 13.4+/-9.2 mmHg) and lower endiastolic ventricular pressures (7.6+/-2.5 vs. 12.6+/-4.0 mmHg) during pre-operative cardiac catheterization indicated a better diastolic ventricular function under chronic Propranolol treatment. CONCLUSION Although high dose Captopril was not evaluated in this study, when compared to patients on low Captopril dosages, infants who received Propranolol treatment showed improvement in heart failure scores, shorter lengths of hospital stay, lower plasma renin activities and better diastolic ventricular functions.

Chances of Employment in a Population of Women and Men after Surgery of Congenital Heart Disease: Gender-Specific Comparisons between Patients and the General Population

It was examined whether women and men (17-45 years) with operated congenital heart disease (CHD) differ with respect to chances of employment. Patients were compared with the general population. Patients (N=314) were classified by type of surgery (curative, reparative, palliative) as indicator of initial severity of disease. The second classification was performed according to a system proposed by the New York Heart Association in order to take subjectively reported impairments into account. Controls (N=1165) consisted of a 10% random sample drawn from the German Socio-Economic Panel. Chances of full- time employment decreased as disease severity increased. Chances of part- time and minor employment were higher in patients than among controls. These general effects were due to male patients, while the employment patterns of women did not differ from the control group. Independently of patient status women were more likely to have lower rates of full- time employment, and the rates of part- time and minor employment were higher. Long- term adaptation to impairments due to congenital heart disease differs between women and men with respect to employment status. While female patients do not differ from the general population, males may lower their engagement in paid work.

Intravenous luteinizing hormone-releasing hormone has no effect on serum N-terminal pro-brain natriuretic peptide in children and adolescents

Background:  Little is known about the acute effects of i.v. luteinizing hormone‐releasing hormone (LHRH) on the heart function, therefore the aim of the present study was to measure N‐terminal pro‐brain natriuretic peptide (N‐BNP) in children, who underwent a diagnostic work up for short stature or delayed puberty.