A survey on Prader-Willi syndrome in the Italian population: prevalence of historical and clinical signs.

Clinical criteria for the diagnosis of Prader-Willi Syndrome (PWS) were established by consensus in 1993 (Holm et al.). Specific molecular testing is now available and the purpose of diagnostic criteria has shifted to identify individuals to test, thus avoiding the expense of unnecessary analysis. The aim of this study was to find clinical indicators to select patients with suspected PWS for laboratory testing. We analyzed the prevalence of clinical signs and symptoms in 147 genetically diagnosed Italian patients with PWS (67 males and 80 females), aged from 9 months to 34.6 years (13.6 +/- 8.3 years), using the consensus diagnostic criteria, and according to age, sex and type of genetic abnormality. The prevalence of several clinical features changed significantly with age, but very few with sex. According to genetic subtypes (deletion vs UPD), only hypopigmentation and acromicria were more frequent in patients with deletion. Some criteria considered as minor or supportive by Holm et al. have higher prevalence than some major criteria. In conclusion, in order to identify patients with suspected PWS to submit to laboratory testing, we recommend a classification of clinical criteria according to age, giving more attention to those so-called minor or supportive criteria.

Cognitive and neuroradiological findings in congenital adrenal hyperplasia.

Nineteen patients with congenital adrenal hyperplasia (CAH) aged over 16 years were given a neuropsychological evaluation; no significant differences with individually matched normal controls were detected. CAH subjects, however, revealed slightly higher IQs with respect to the expected distribution. No significant learning disabilities could be detected. Fifteen patients underwent nuclear magnetic resonance (NMR); 4 subjects showed small areas of increased signal intensity in the white matter, without prevalence of side; this finding did not correlate with clinical and cognitive characteristics. The results are discussed in the light of possible hormonal influences.

Growth hormone bioactivity, insulin-like growth factors (IGFs), and IGF binding proteins in obese children.

In obese children, both spontaneous and stimulated growth hormone (GH) secretion are impaired but a normal or increased height velocity is usually observed. This study was undertaken to explain the discrepancy between impaired GH secretion and normal height velocity. We evaluated the GH bioactivity (GH-BIO), GH serum level by immunofluorimetric assay (GH-IFMA), insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 in 21 prepubertal obese children (13 boys and eight girls) aged 5.7 to 9.4 years affected by simple obesity and in 32 (22 boys and 10 girls) age- and sex-matched normal-weight controls. The results were as follows (obese versus [v] controls): GH-IFMA, 4.84 +/- 3.54 v 23.7 +/- 2.04 microg/L (P < .001); GH-BIO, 0.60 +/- 0.45 v 1.84 +/- 0.15 U/mL (P < .001); IGF-I, 173.8 +/- 57.2 v 188.6 +/- 132.6 ng/mL (nonsignificant); IGF-II, 596.1 +/- 139.7 v 439.3 +/- 127.4 ng/mL (P < .001); IGFBP-1, 23.25 +/- 14.25 v 107 +/- 165.7 ng/mL (P < .05); IGFBP-2, 44.37 +/- 62.18 v 385.93 +/- 227.81 ng/mL (P < .001); IGFBP-3, 3.31 +/- 0.82 v 2.6 +/- 0.94 microg/mL (P < .05); and IGFs/IGFBPs, 1.32 +/- 0.32 v 1.07 +/- 0.34 (P < .05). In conclusion, in prepubertal obese children, not only immunoreactive but also bioactive GH concentrations were low. In these subjects, therefore, nutritional factors and insulin may contribute to sustain normal growth also by modulating several components of the IGF-IGFBP system.

Hypersomnia in the Prader Willi syndrome: clinical-electrophysiological features and underlying factors.

OBJECTIVE: Excessive daytime sleepiness is a common symptom in Prader Willi syndrome (PWs). Sleep disordered breathing (SDB) and narcoleptic traits such as REM sleep onsets (SOREMPs) have been reported in these subjects. We evaluated nighttime and daytime sleep patterns in patients with PWs in order to clarify the nature of their hypersomnia. DESIGN AND METHODS: We performed overnight continuous EEG-polysomnographic studies (with breathing monitoring included) in 14 subjects (6 M,8 F; mean age 17 years, range 8-37) affected by PWs unselected for sleep disturbances. Ten patients underwent a Multiple Sleep Latency Test (MSLT) the day following the nocturnal sleep studies. Patients assessment was completed by means of immunogenetic characterization. RESULTS: Nocturnal polysomnographic investigation documented sleep related breathing abnormalities such as central apneas, hypopneas or hypoventilation which mainly occurred during REM sleep in 8 subjects and did not cause sleep disruption. Only 4 subjects presented an increase in the Respiratory Disorder Index (RDI) slightly above the normal limits. In 8 subjects out of 10, with and without SDB, the mean daytime sleep latency could be considered abnormal according to the Tanner staging of pubertal development. Five patients showed at least two SOREMPs at MSLT. Subjects with and without SOREMPs had, respectively, a mean age of 18.6 SD 7.9 (4 M, 1 F) and 14.5 SD 2.9 (4 F, 1 M). The paternal deletion:uniparental dysomy ratio at genotypic characterization was 4:1 and 3.5:1 in subjects with and without SOREMPs, respectively. No patient presented DR-15 nor Dq-6. CONCLUSIONS: Excessive sleepiness is a frequent disturbance in PWs. Subgroups of PW patients show hypersomnolence and SOREMPs. Sleep disordered breathing appears to have a limited role in the genesis of hypersomnia which not seems on the other hand attributable to the coexistence of narcolepsy phenotype. Hypersomnia in PW syndrome is likely to mainly be attributable to a primary hypothalamic dysfunction. The potential interacting role of other factors such as subjects age, sex and genetic pattern is suggested and deserve further investigation.

The influence of dietary education in diabetic children.

The aim of our study was to evaluate the efficacy of dietary education in inducing modification of the diet and to measure biochemical parameters in 36 children and adolescents with IDDM. At the beginning of the study, each patient was evaluated as follows: food intake (by the method of the 24-h recall for 3 days), auxological parameters, biochemical parameters. Thereafter a program of nutritional guidelines was provided. Subsequent meetings took place at 1-month-intervals. The study ended 3 months later, when all the parameters were completely revalued. We observed improved nutrition in our patients both in terms of total caloric intake and calorie distribution. In particular there was an increase in carbohydrates and a reduction in lipids, reaching the percentage levels recently recommended. With a reduction in lipid intake a significant decrease in LDL cholesterol and a significant increase in HDL cholesterol were noticed in our patients. These modifications are very important for the prevention of arteriosclerosis and thus macrovascular disease. We maintain that dietary education plays an important role in helping children and adolescents with IDDM to follow a suitable diet.

Waist circumference as a predictor of cardiovascular and metabolic risk factors in obese girls.

OBJECTIVES: (a). to explore the relationship between waist circumference and certain cardiovascular risk factors in a group of girls; and (b). to assess the clinical relevance of waist circumference in identifying girls with higher cardiovascular risk across puberty. SUBJECTS AND METHODS: One-hundred and fifty-five overweight or obese girls aged 5-16 y were recruited. Overweight and obesity were defined on the basis of BMI, according to Cole. RESULTS: : Waist circumference was significantly correlated with plasma insulin (r=0.43; P<0.001), systolic blood pressure (r=0.22; P=0.007) and IR(HOMA) (r=0.40; P<0.001). A multivariate linear correlation analysis showed that, when adjusted for age and Tanner stage, waist circumference was significantly associated with plasma insulin (r(2)=0.23; P<0.01), IR(HOMA) (r(2)=0.17; P<0.02), systolic and diastolic blood pressure (r(2)=0.20; P=0.006 and r(2)=0.32; P<0.001, respectively). A logistic regression analysis, using IR(HOMA) as the dependent variable, showed that waist circumference was a significant independent risk factor of insulin resistance (IR(HOMA)>or=2.6) in this group of girls (OR 1.10; 95% CI 1.03-1.18; P=0.003), independently of their age and Tanner stage. CONCLUSIONS: Waist circumference of these girls was independently associated with certain cardiovascular risk factors, in particular insulin resistance and diastolic blood pressure, independently of age and Tanner stage. Thus suggesting that waist circumference may be reasonably included in clinical practice as a simple tool that may help to identify sub-groups of obese girls at higher metabolic risk across puberty.

Final height in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: the Italian experience.

OBJECTIVE: To investigate the influence of target height (TH), gender, phenotype, glucocorticoid formulation and age at onset of treatment on final height (FH) in patients with 21-hydroxylase deficiency (21OHD). PATIENTS: Clinical data of 93 patients--46 simple virilizing (SV), 35 salt-wasting (SW) and 12 late onset (LO)--were collected in six pediatric endocrinology units in Italy. RESULTS: FH and TH were always below the mean height of the general population (mean FH, SDS: SW patients -1.3 +/- 1.2, SV patients -1.8 +/- 0.9, LO patients -1.7 +/- 1.1; mean TH, SDS: SW patients -0.6 +/- 0.8, SV patients -0.7 +/- 0.9, LO patients -1.4 +/- 1.3). FH was significantly below TH in patients with classic form (SW and SV, p <0.001), but not in LO patients. In classic form, TH seems to be related to FH, followed by age at onset of therapy and by steroid formulation, these variables explaining 30% of FH variance. CONCLUSIONS: In the classic form, substitutive therapy started before 21 months of age improved the long-term outcome. Lower TH in LO patients could be due to undiagnosed non-classic 21OHD in some of their parents. FH in LO patients seems not to benefit from corticosteroid therapy, even if late diagnosis may partly account for this result.

Childhood obesity: results of a multicenter study of obesity treatment in Italy.

The prevalence of pediatric obesity is increasing and many patients are followed by specialized centers or private doctors. The aim of this study was to verify short- and medium term results of a therapeutic approach based on nutritional intervention in a large pediatric population: 1383 subjects (695 females, 688 males) aged 10.1 +/- 2.7 yr, followed in 11 pediatric departments in Italy. No difference was found between centers in age, height, weight, BMI and IBW. The drop-out rate after the first visit was 30.2% (58.1% IBW > 140%) in females and 34.2% (70.7% IBW > 140%) in males. After two years of follow-up only 9.7% of females and 6.4% of males remained on treatment. Of these patients only 7.3% of females and 6.4% of males had IBW < 120%. These data show that an approach based on nutritional intervention alone is not sufficient for long-term treatment of pediatric obesity. Only an approach started early and involving the family can produce permanent results.

Age-related changes in excitability of nociceptive flexion reflex. An electrophysiological study in school-age children and young adults.

By stimulating the sural nerve at the retromalleolar level and recording EMG response from biceps femoris muscle two components can be evoked: RII (shorter latency, lower threshold, non-nociceptive) and RIII (longer latency, higher threshold, nociceptive). RIII reflex represents a useful tool for pain research in humans since a close correlation exists between the reflex threshold and that of pain. In our study, latency, amplitude, duration and threshold of RII and RIII reflexes were investigated in school-age children (aged 7-14 years) and young adults. RIII threshold was significantly lowered in children, while the other parameters were similar in both groups. Our data suggest the existence of a reduced inhibitory descending control in nociceptive spinal neurones in children.

[Prader-Willi syndrome]. / La sindrome di Prader-Willi.

Prader-Willi syndrome (PWS) is the most frequent cause of secondary obesity, characterized by neonatal hypotonia, dysmorphic facies, acromicria, hypogonadism, stunted growth, obesity, behavioural disturbances and cognitive impairment. Clinical diagnosis is confirmed by alteration of imprinted genes on the proximal long arm of chromosome 15 (15q11-13) for deletion, translocation, uniparental disomy for maternal chromosome 15 or imprinting center defect. Methylation test is the most reliable test for diagnosis. This issue explains diagnostic tests, clinical, metabolic, endocrinological features, and the most frequent complications observed in this syndrome. Precocious diagnosis and multidisciplinary approach allow in these patients to prevent the severe obesity and linked complications.

[The use of highly purified glucomannan-based fibers in childhood obesity]. / Impiego di fibre a base di glucomannano altamente purificato nell'obesità infantile.

To evaluate the effectiveness of highly purified glucomannan in childhood obesity a study has been carried out in 23 obese children (12 boys and 11 girls, aged 5.2-15.8 years), with excess weight of 51 +/- 16%, treated with 2-3 caps twice a day of glucomannan fibres (DICOMAN 5:2-3 gr/die), and in 30 obese children (aged 5-18 years) with excess weight of 51 +/- 10%, studied as controls. After a three-days food recall, a balanced diet with adequate caloric intake was provided to all obese children. In all patients before and 2-4 months after the auxological data (weight, height, weight excess) and laboratory data (serum levels of cholesterol, HDL, triglycerides, glucose, fructosamine, glycosylated hemoglobin, RBC, WBC, hemoglobin, iron, calcium, Cu and Zn) have been determined. Excess weight and triglycerides levels were significantly decreased in treated obese patients than in obese controls 4 months after the beginning of the study. A decrease of cholesterol levels was also observed in treated obese patients, but not in controls, whereas serum iron, calcium, copper and zinc persisted unchanged. No important side-effects were observed in treated patients. On the basis of our results highly purified glucomannan fibres may be employed with effectiveness in obese and dyslipidemic children together with diet.

[Buschke's scleredema and carditis: a clinical case]. / Scleredema di Buschke e cardite: un caso clinico.

An 11-year old girl who presented non-pitting edema of the face and neck, shoulder pain and a gallop rhythm about 10 days after a febrile episode with sore throat is described. The mask-like facial appearance and limited movement of the neck led to suspect scleredema which may be accompanied by carditis. Skin and muscle biopsy findings confirmed the diagnosis. Cardiac involvement included a gallop rhythm persisting for 6 months, ECG changes consisting in transitory T-wave inversion in leads II and V2 - V4, a transitory pericardial function rub and hepatomegaly due to right-sided failure which responded to digitalization. In this case the presence of a gallop rhythm and elevated ASLO titer led to an initial diagnosis of acute rheumatic fever; dermatomysitis and sclerodermia are also to be considered in the differential diagnosis of scleredema of Buschke. In our patient the edema resolved completely within 12 months, the gallop rhythm within 6 months and the ECG became normal after 8 months.

[Experience in diet therapy of child obesity]. / Esperienze di dietoterapia nell'obesità infantile.

During the last 14 years 1620 children and adolescents, 806 boys and 814 girls, aged 2-20 yrs, were referred for overweight as outpatients to the Pediatric Endocrine Center of the University of Pavia. On first admission 170 (10%) of the 1620 subjects had a percent overweight of less than 20% referred to ideal weight for height; 350 (22%) patients with overweight ranging from 25 to plus 100 were lost to follow up. We report our dietary management on 1100 children with percent overweight between 25-120, treated for a period of at least 3 months to a maximum of 7 years (mean 3 yrs). All patients were provided with a physiological diet with an adequate or slightly reduced caloric intake for their height (P 15%, F 25%, C 60%). A regular physical activity was recommended to our patients. Before they started the diet patients kept a daily food diary for three days, which included recording information about what food was eaten, how it was prepared and the time at which it was consumed. Food recalls showed a higher caloric intake for height and age with fat and protein excess, especially of animal origin. A lot of snacks, particularly sweets, and soft drinks were consumed during the day.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hyperthyroidism in children (author's transl)]. / L'ipertiroidismo nel bambino.

The present paper analyzes the causes, signs and symptoms of hyperthyroidism in children and the problems, complications and results associated with the various therapeutic regimes. Childhood hyperthyroidism is usually due to Grave's disease, an autoimmune thyroid disease. Genetic factors are also involved in its development. The diagnosis and in particular the differential diagnosis with Hashimoto's thyroiditis are discussed. Treatment of Graves' disease is controversial, but medical therapy is commonly accepted as the treatment of choice. Some dosage schedules of antithyroid drugs are considered, and some techniques for predicting remission status and relapse of disease are reported. Both the minor and more serious complications of medical therapy are examined. Careful follow-up for the development of hypothyroidism is advocated, especially in patients treated with radiation or surgery. Autonomous hyperfunctioning thyroid adenoma is rare, but occurs even in childhood, and can degenerate into carcinoma.

Pituitary height and neuroradiological alterations in patients with Prader-Labhart-Willi syndrome.

Prader-Willi syndrome (PWS), a genetic disorder due to an alteration in the paternally derived long arm of chromosome 15, is characterized by a complex clinical picture (short stature, obesity, hypogonadism) that seems to be referable to as a central hypothalamic/pituitary dysfunction. To determine whether there is any diminution in the anterior pituitary gland or other neuroradiological alterations, we retrospectively analysed 91 patients with PWS (42 females, 49 males; age range: 0.7-16.8 years) by cerebral magnetic resonance imaging (MRI). Of these 91 patients, MRI analysis showed a reduction in pituitary height in 45 patients (49.4%), a complete absence of the posterior pituitary bright spot in six patients (6.6%) and other neuroradiological alterations in ten patients (11%). Altogether, neuroradiological alterations were present in 61 of the 91 (67%) patients. Our results indicate that neuroradiological alterations are more frequent in PWS patients than has been reported to date.

Death during GH therapy in children with Prader-Willi syndrome: description of two new cases.

A few cases of death worldwide during GH treatment in pediatric patients with Prader-Willi syndrome (PWS) have been recently described. The evaluation of further cases is needed to better identify possible causal mechanism(s), as well as to suggest some additional guidelines for prevention. We report the death of 2 additional children with genetically confirmed PWS in the first months of GH therapy. Case 1: This 3.9-yr-old girl was born at 39 weeks gestation. Low GH response to two stimulation tests was observed. GH administration was started at the age of 3.5 yr (0.33 mg/kg per week), when the patient was at 130% of her ideal body weight (ibw). Hypertrophy of adenoids was previously demonstrated. Snoring and sleep apnea were present before GH treatment, and did not increase during therapy. Four months later she died at home suddenly in the morning. Case 2: This patient was a 6.3-yr-old boy. He was born at term after an uneventful pregnancy. At the age of 6 yr, his weight was at 144% of his ibw. He showed reduced GH secretion during provocation tests, and GH therapy was started (0.20 mg/kg per week). The previously reported nocturnal respiratory impairment had worsened after beginning GH administration. Tonsils and adenoids hypertrophy were noted. At the age of 6.3 yr he died at home in the morning following an acute crisis of apnea. These additional cases seem to confirm that some children with PWS may be at risk of sudden death at the beginning of GH therapy.

Height, bone mineral density and bone markers in congenital adrenal hyperplasia.

AIM: To evaluate height, bone growth, areal bone mineral density (aBMD), volumetric bone mineral density (vBMD) and markers of bone turnover in a group of patients affected by congenital adrenal hyperplasia (CAH). PATIENTS: There were 50 patients (23 males, 27 females), aged 1-28 years, affected by CAH due to 21-hydroxylase deficiency: 27 with the salt-wasting (SW); 14 with the simple virilizing (SV), and 9 with the nonclassical (NC) forms. METHODS: Bone morphometry was evaluated with the metacarpal index (MI) and lumbar aBMD and vBMD (L2-L4) by dual energy X-ray absorptiometry. Serum osteocalcin was used as a marker of bone formation, while urinary cross-linked N-telopeptides of type-I collagen and free deoxypyridinoline levels were evaluated as indexes of bone resorption. RESULTS: The height standard deviation score (SDS) was -0.41 +/- 1.4 in SW patients, -0.01 +/- 1.9 in SV patients, and -0.01 +/- 2.3 in NC patients. There was no significant difference among groups and against zero. The MI SDS was also not different between groups and against zero. aBMD was significantly lower in the pubertal patients compared with normal values, but only when patients with the SW and SV forms were considered together (p < 0.05). vBMD was significantly reduced in all patients with the classical form. Bone markers were not different in patients and controls. CONCLUSION: Our study shows that normal height can be attained in CAH patients; however, an impairment in bone growth and mineralization may be found in adolescents and young adults affected by the classical form.

Ruvalcaba syndrome: a case report.

An 11-year-old child with mental retardation and short stature was examined and found to be affected with some skeletal malformations. The clinical and radiological pattern of limb alterations was particularly suggestive of the features of Ruvalcaba syndrome. A complete examination confirmed the diagnosis and showed ocular involvement. To the best of our knowledge this is first published confirmation of Ruvalcaba syndrome.

Partial response after intensive chemotherapy for adrenal cortical carcinoma in a child.

Adrenocortical carcinoma (ACC) in childhood is a rare tumor with high fatality rate. Available reports provide event free survival rates ranging between 10 to 50%. Optimal treatment has not yet been established; surgery plays a major role, and the value of adjuvant chemotherapy needs to be evaluated further, especially in children who develop recurrent disease and those with metastases at diagnosis. Optimal therapy of ACC has not been established. Surgery has been curative after complete tumor resection. Children with inoperable, recurrent and metastatic ACC have been treated with O,P'DDD, with response rates ranging from 10 to 60% in different series [7,11-20]. Radiotherapy [21] and other anti-cancer drugs have been used [4-22] but their efficacy has not been established. Combination chemotherapy containing oncovin, cisPlatinum, epipodophyllotoxin and cyclophosphamide (OPEC) produced regression of metastatic ACC in a 5-year-old male [23]. We report one girl with relapsed disseminated ACC who showed good, even if temporary, control of the disease, with disappearance of lung, liver and spleen metastases, and marked reduction of the adrenal mass, following combined chemotherapy according to the "eight-drugs-in-one-day" protocol.

[Definition of obesity in childhood: criteria and limits]. / Criteri e limiti della definizione di obesità nell'età evolutiva.

A rigorous scientific definition of obesity in childhood is not yet available: in fact, there is not agreement among researchers on the adiposity index to use and on the best cut-off to define overweight and obesity. In this review, the reference methods for the diagnosis of childhood obesity in the clinical practice in Italy are reported. All the statements are based on evidences of the literature and obtained the consensus of the pediatricians of the Study Group on Obesity of the Italian Society of Pediatric Diabetology and Endocrinology. Obesity is caused by an excess of body fat. The methods more frequently used to measure body fat are the measure of subcutaneous skinfold thickness, bioimpedence assessment and DXA. The measure of skinfolds is preferable in the clinical setting because it is easy to use and cheap, although reproducibility is modest. Triceps skinfold is commonly used to define obesity: children with triceps higher than the 85(th) centile for age and gender, using Tanner's tables, are obese. An estimation of fat mass obtained, for instance, with skinfolds is always suggested in addition to the measure of weight and height. It is possible to define a child as obese calculating the ratio between weight (kg) and height squared (m). This ratio is an index, called body mass index (BMI), which is strictly associated to the level of adiposity in children, reproducible and valid. The BMI was recently proposed as the reference index for the diagnosis of childhood obesity at the international level. The use of the centiles of BMI may offer useful information on the changes of weight excess, simplifying the follow-up of the patient and the sensitivity to treatment. The cut-off limits of BMI to define overweight or obesity are still debated. However, in agreement with Cole et al., the choice to use the BMI cut-offs centiles passing through the adult BMI cut-off of 30, is reasonable. However, it is always preferable to use population specific BMI reference tables.