The Italian National Survey for Prader-Willi syndrome: an epidemiologic study.

Twenty-five medical centers and the Prader-Willi Syndrome (PWS) Association collaborated on a study which attempted to identify all people with genetically confirmed diagnosis of PWS living in Italy. Investigators of the participating centers contacted PWS subjects and/or their family, filled in a specially developed form with the required data and forwarded this information by email. The study identified 425 subjects (209 males and 216 females, between the ages of 0.4-46.7). Two hundred thirty-eight patients had del15, 104 had UPD15, 4 demonstrated a translocation affecting chromosome 15 and 79 showed a positive methylation test. There were fewer subjects found over the age of 35, probably due to the low rate of identification of older PWS patients as well as the high mortality rate. There were a greater number of male children and adolescents with PWS whilst, amongst adults, there were more females. As expected, the majority of subjects with PWS were obese, especially in adult life. Nevertheless, it is noteworthy that 26% of patients aged between 6 and 17 were normal weight. A total of 212 subjects had received GH treatment, of which 141 were still receiving therapy, while the remaining 71 had stopped. In children and adolescents (233 cases), 89 subjects had never undergone GH therapy. Eighteen PWS patients had died in the past 20 years. Obesity-related cardiovascular and respiratory diseases were the cause of death, both during childhood and after 18 years of age. Three children died suddenly whilst undergoing GH therapy. Respiratory infection and cardiac illness were the causes of death in two cases. There was no definitive cause of death found in the third case. Overall, there was no increase in number of deaths during GH treatment, suggesting that GH administration in patients with PWS, as a group, does not increase the risk of death.

Endocrine and growth features in childhood craniopharyngioma: a mono-institutional study.

OBJECTIVE: To evaluate growth and endocrine features in children with craniopharyngioma who were treated and followed up by a single institution between 1976 and 2004. PATIENTS: The records of 32 children, 18 males and 14 females, were evaluated. The mean follow-up period was 6.3 years. RESULTS: At presentation, the most common symptoms were headache, nausea and vomiting, visual impairment, and neurological changes. Some patients presented signs or symptoms of isolated or combined endocrine disorder (five polyuria and polydipsia, five growth failure, two precocious puberty, eight obesity or overweight). After tumour treatment, multiple pituitary hormonal deficiencies, especially growth hormone (GH) deficit (GHD) were found and required hormonal replacement therapy. Eight children grew normally without GH despite GHD. Hypothalamic involvement was observed in ten patients; obesity was frequent and was often associated with hyperinsulinism and hyperphagia. CONCLUSION: Anterior and posterior pituitary deficiencies following surgery are present in all patients. The growth pattern is heterogeneous.

Different inactivating mutations of the mineralocorticoid receptor in fourteen families affected by type I pseudohypoaldosteronism.

We have analyzed the human mineralocorticoid receptor (hMR) gene in 14 families with autosomal dominant or sporadic pseudohypoaldosteronism (PHA1), a rare form of mineralocorticoid resistance characterized by neonatal renal salt wasting and failure to thrive. Six heterozygous mutations were detected. Two frameshift mutations in exon 2 (insT1354, del8bp537) and one nonsense mutation in exon 4 (C2157A, Cys645stop) generate truncated proteins due to premature stop codons. Three missense mutations (G633R, Q776R, L979P) differently affect hMR function. The DNA binding domain mutant R633 exhibits reduced maximal transactivation, although its binding characteristics and ED(50) of transactivation are comparable with wild-type hMR. Ligand binding domain mutants R776 and P979 present reduced or absent aldosterone binding, respectively, which is associated with reduced or absent ligand-dependent transactivation capacity. Finally, P979 possesses a transdominant negative effect on wild-type hMR activity, whereas mutations G633R and Q776R probably result in haploinsufficiency in PHA1 patients. We conclude that hMR mutations are a common feature of autosomal dominant PHA1, being found in 70% of our familial cases. Their absence in some families underscores the importance of an extensive investigation of the hMR gene and the role of precise diagnostic procedures to allow for identification of other genes potentially involved in the disease.

Assessment of skeletal maturity of the hand-wrist and knee: A comparison among methods.

This study evaluated the influence of height growth and nutritional status on skeletal maturation of the knee and hand-wrist. Radiographs of 589 subjects (250 girls and 339 boys) from 2 to 15 years were rated according to Greulich-Pyle, TW-20 bone and TW-RUS, RWT knee, and FELS hand-wrist methods and a method combining FELS and RWT indicators. The subjects were referred to the Genoa University Paediatric Department from 1980 to 1987 for short stature, simple obesity, or acute diseases. Bone age was closer to chronological age using the RWT knee method rather than the hand-wrist methods, while bone age assessed at the hand-wrist was closely related to height and BMI. When skeletal maturation was delayed, Greulich-Pyle, TW-20-bone, TW-RUS, and FELS bone ages tended to be lower than RWT knee estimates. Conversely, if maturation was advanced the hand-wrist estimates tended to be higher than RWT knee bone ages. The combined estimates are close to FELS bone age values. These findings show true intraindividual variability of skeletal maturity at the hand-wrist and knee. A certain "laziness" in knee maturation seems to be confirmed. Am. J. Hum. Biol. 12:610-615, 2000. Copyright 2000 Wiley-Liss, Inc.