ABSTRACT
OBJECTIVE: Prader-Willi Syndrome is a common etiology of syndromic obesity that is typically caused by either a paternal microdeletion of a region in chromosome 15 (microdeletions) or a maternal uniparental disomy of this chromosome. The purpose of this study was to describe the most significant clinical features of 35 Brazilian patients with molecularly confirmed Prader-Willi syndrome and to determine the effects of growth hormone treatment on clinical outcomes. METHODS: A retrospective study was performed based on the medical records of a cohort of 35 patients diagnosed with Prader-Willi syndrome. The main clinical characteristics were compared between the group of patients presenting with microdeletions and the group presenting with maternal uniparental disomy of chromosome 15. Curves for height/length, weight and body mass index were constructed and compared between Prader-Willi syndrome patients treated with and without growth hormone to determine how growth hormone treatment affected body composition. The curves for these patient groups were also compared with curves for the normal population. RESULTS: No significant differences were identified between patients with microdeletions and patients with maternal uniparental disomy for any of the clinical parameters measured. Growth hormone treatment considerably improved the control of weight gain and body mass index for female patients but had no effect on either parameter in male patients. Growth hormone treatment did not affect height/length in either gender. CONCLUSION: The prevalence rates of several clinical features in this study are in agreement with the rates reported in the literature. Additionally, we found modest benefits of growth hormone treatment but failed to demonstrate differences between patients with microdeletions and those with maternal uniparental disomy. The control of weight gain in patients with Prader-Willi syndrome is complex and does not depend exclusively on growth hormone treatment.
Subject(s)
Adolescent , Child , Female , Humans , Male , Human Growth Hormone/therapeutic use , Prader-Willi Syndrome/drug therapy , Age Factors , Body Composition , Body Mass Index , Brazil , Chromosome Deletion , /genetics , Follow-Up Studies , Intellectual Disability/genetics , Obesity/complications , Obesity/genetics , Prader-Willi Syndrome/genetics , Prader-Willi Syndrome/pathology , Retrospective Studies , Sex Factors , Seizures/genetics , Treatment OutcomeABSTRACT
Seventy-two patients with clinical diagnoses of Prader-Willi (PWS; n = 28 patients) or Angelman syndromes (AS; n = 44 patients) were submitted to chromosome analysis, SNRPN-SNURF exon 1 methylation assay, and microsatellite genotyping. Analysis of the methylation pattern confirmed the PWS diagnosis in 18 out of 28 patients and the AS diagnosis in 20 out of 44 patients. FISH and microsatellite analysis detected a deletion in 30 patients (14 PWS and 16 AS). Eight patients had normal FISH results (4 PWS and 4 AS); microsatellite markers showed that these patients had a uniparental disomy (UPD). Based on this study, we propose a strategy for the routine diagnosis of these syndromes that consists of the following steps: 1) methylation analysis, which does not require parental samples; 2) microsatellite genotyping of patient and parents to differentiate deletions, UPD and imprinting mutations; and 3) FISH for otherwise uninformative cases, and whenever parental samples are not available. Of the 34 patients whose PWS or AS diagnoses were not confirmed by laboratory tests, five presented a small extra marker chromosome, identified in three of them as an inv dup(15). One AS patient carried a balanced t(15;15) translocation associated with paternal UPD. Therefore G-banded chromosome analysis should be performed on all such patients, to detect possible structural rearrangements