Aberrant brain intra- and internetwork functional connectivity in children with Prader-Willi syndrome.

PURPOSE: Prader-Willi syndrome (PWS) suffers from brain functional reorganization and developmental delays during childhood, but the underlying neurodevelopmental mechanism is unclear. This paper aims to investigate the intra- and internetwork functional connectivity (FC) changes, and their relationships with developmental delays in PWS children. METHODS: Resting-state functional magnetic resonance imaging datasets of PWS children and healthy controls (HCs) were acquired. Independent component analysis was used to acquire core resting-state networks (RSNs). The intra- and internetwork FC patterns were then investigated. RESULTS: In terms of intranetwork FC, children with PWS had lower FC in the dorsal attention network, the auditory network, the medial visual network (VN) and the sensorimotor network (SMN) than HCs (FWE-corrected, p < 0.05). In terms of internetwork FC, PWS children had decreased FC between the following pairs of regions: posterior default mode network (DMN) and anterior DMN; posterior DMN and SMN; SMN and posterior VN and salience network and medial VN (FDR-corrected, p < 0.05). Partial correlation analyses revealed that the intranetwork FC patterns were positively correlated with developmental quotients in PWS children, while the internetwork FC patterns were completely opposite (p < 0.05). Intranetwork FC patterns showed an area under the receiver operating characteristic curve of 0.947, with a sensitivity of 96.15% and a specificity of 81.25% for differentiating between PWS and HCs. CONCLUSION: Impaired intra- and internetwork FC patterns in PWS children are associated with developmental delays, which may result from neural pathway dysfunctions. Intranetwork FC reorganization patterns can discriminate PWS children from HCs. REGISTRATION NUMBER ON THE CHINESE CLINICAL TRAIL REGISTRY: ChiCTR2100046551.

Cardiac rhabdomyoma as a possible new prenatal sonographic feature of Prader-Willi syndrome.

We describe a unique case of a pregnancy with fetal Prader-Willi syndrome (PWS). A 40-year-old pregnant woman prenatally presented with polyhydramnios, decreased fetal movements, fetal growth restriction with normal Doppler study, and fetal cardiac rhabdomyoma, a possible new sonographic markers for PWS, at 31 weeks of gestation. The newborn had hypotonia and feeding difficulty. Molecular genetic study showed a normal copy number of the 15q11.2-q13.1 chromosomal region but hypermethylation pattern of this region, indicating PWS. Other than the combination of polyhydramnios, fetal growth restriction, and decreased fetal movements, cardiac rhabdomyoma was detected and possibly associated with PWS. In conclusion, PWS should be listed in differential diagnoses if fetuses having the following perinatal factors: polyhydramnios, decreased fetal movements, and growth restriction. Finally, cardiac rhabdomyoma, observed in this case, might possibly be associated with PWS, although further studies to confirm are needed.

Cerebellar Volumes Associate with Behavioral Phenotypes in Prader-Willi Syndrome.

The objective of this study was to investigate lobule-specific cerebellar structural alterations relevant to clinical behavioral characteristics of Prader-Willi syndrome (PWS). We performed a case-control study of 21 Japanese individuals with PWS (age; median 21.0, range 13-50 years, 14 males, 7 females) and 40 age- and sex-matched healthy controls with typical development. Participants underwent 3-Tesla magnetic resonance imaging. Three-dimensional T1-weighted images were assessed for cerebellar lobular volume and adjusted for total intracerebellar volume (TIV) using a spatially unbiased atlas template to give a relative volume ratio. A region of interest analysis included the deep cerebellar nuclei. A correlation analysis was performed between the volumetric data and the clinical behavioral scores derived from the standard questionnaires (hyperphagia, autism, obsession, and maladaptive index) for global intelligence assessment in paired subgroups. In individuals with PWS, TIV was significantly reduced compared with that of controls (p < 0.05, family-wise error corrected; mean [standard deviation], 1014.1 [93.0] mm3). Decreased relative lobular volume ratios were observed in posterior inferior lobules with age, sex, and TIV as covariates (Crus I, Crus II, lobules VIIb, VIIIa, VIIIb, and IX). However, increased ratios were found in the dentate nuclei bilaterally in individuals with PWS (p < 0.01); the mean (standard deviation) × 10-3 was as follows: left, 1.58 (0.26); right, 1.67 (0.30). The altered lobular volume ratios showed negative correlations with hyperphagic and autistic characteristics and positive correlations with obsessive and intellectual characteristics. This study provides the first objective evidence of topographic patterns of volume differences in cerebellar structures consistent with clinical behavioral characteristics in individuals with PWS and strongly suggests a cerebellar contribution to altered functional brain connectivity in PWS.

Evolution of Hip Dysplasia in Pediatric Patients With Prader-Willi Syndrome Treated With Growth Hormone Early in Development.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by obesity, hypotonia, feeding difficulties, obesity, musculoskeletal manifestations including scoliosis, and hip dysplasia (HD). The aim of this study was to characterize the clinical and radiographic evolution of HD in the pediatric PWS population. METHODS: The authors performed a retrospective cohort study of 72 patients (147 anteroposterior pelvic radiographs) between January 2004 and December 2016. Center-edge angle (CEA) of Wiberg, acetabular index (AI), and neck-shaft angle (NSA) were measures in all hips. The relationship between radiographic and demographic parameters of age, sex, and body mass index z-score (BMIzs) were assessed. RESULTS: A total of 274 radiographic measurements were performed and analyzed in 72 patients. The mean CEA, AI, and NSA were 21.8±7.1 degrees (range, 5 to 35 degrees), 16.7±7 degrees (range, 5 to 45 degrees), and 142±8.5 degrees (range, 128 to 165 degrees), respectively. HD was diagnosed in 79 (29%) hip radiographs and varied significantly between the age groups (P<0.01). A statistically significant association was identified between age and CEA [ß coef, 0.80; 95% confidence interval (CI), 0.6-1; P<0.01], AI (ß coef, -0.90; 95% CI, -1.1 to -0.7; P<0.01), and NSA (ß coef, -1.11; 95% CI, -1.4 to -0.9; P<0.01) angles. Sex and BMIzs were not identified as independent predictors of radiographic hip angles (P>0.1). CONCLUSIONS: The present study demonstrated favorable evolution of hip radiographic parameters in the PWS population treated with growth hormone early in development. This finding should prompt orthopedists to consider observation alone in the management algorithm for HD in patients with PWS. LEVELS OF EVIDENCE: Level III-a retrospective comparative study.

Brain-stem serotonin transporter availability in maternal uniparental disomy and deletion Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a rare condition because of the deletion of paternal chromosomal material (del PWS), or a maternal uniparental disomy (mUPD PWS), at 15q11-13. Affective psychosis is more prevalent in mUPD PWS. We investigated the relationship between the two PWS genetic variants and brain-stem serotonin transporter (5-HTT) availability in adult humans. Mean brain-stem 5-HTT availability determined by [123I]-beta-CIT single photon emission tomography was lower in eight adults with mUPD PWS compared with nine adults with del PWS (mean difference -0.93, t = -2.85, P = 0.014). Our findings confirm an association between PWS genotype and brain-stem 5-HTT availability, implicating a maternally expressed/paternally imprinted gene, that is likely to account for the difference in psychiatric phenotypes between the PWS variants. Declaration of interest None.

Visceral adipose tissue increases shortly after the cessation of GH therapy in adults with Prader-Willi syndrome.

GH therapy in pediatric patients with Prader-Willi syndrome (PWS) improves body composition, but discontinuation of GH after achieving adult height has been implicated in its deterioration. Although there is evidence for the deleterious effects of visceral adipose tissue (VAT) rather than subcutaneous adipose tissue (SAT) on the development of obesity-related complications, the effects of GH discontinuation on fat distribution in adults with PWS has not been fully investigated. Therefore, we utilized dual-energy X-ray absorptiometry (DEXA) and abdominal computed tomography (CT) to compare the fat distribution between before and 6 months or 12 months after the cessation of GH therapy in 7 adult PWS patients. GH therapy was initiated at a mean age of 4.1 ± 1.4 years and discontinued at a mean age of 18.9 ± 1.8 years. Serum IGF-1 levels were decreased by discontinuation of GH therapy. Fat mass was significantly increased 6 and 12 months after GH cessation, whereas muscle mass and bone mineral density were unchanged during both study periods. Abdominal CT analysis revealed that elevations in fat mass were due to increases in VAT rather than SAT. Circulating low-density lipoprotein (LDL) cholesterol levels were significantly elevated 6 months after GH cessation. In conclusion, discontinuation of GH therapy caused rapid increases in visceral adipose tissue and LDL cholesterol levels. These findings indicate that continuation of GH therapy may be a therapeutic option to maintain body composition; however, further studies regarding the long-term benefits and adverse effects of GH therapy in adults with PWS are required.

Microstructural white matter tract alteration in Prader-Willi syndrome: A diffusion tensor imaging study.

Prader-Willi Syndrome (PWS) is a genetic disorder characterized by infantile hypotonia, hyperphagia, hypogonadism, growth hormone deficiency, intellectual disability, and severe emotional and behavioral problems. The brain mechanisms that underpin these disturbances are unknown. Diffusion tensor imaging (DTI) enables in vivo investigation of the microstructural integrity of white matter pathways. To date, only one study has used DTI to examine white matter alterations in PWS. However, that study used selected regions of interest, rather than a whole brain analysis. In the present study, we used diffusion tensor and magnetic resonance (T 1-weighted) imaging to examine microstructural white matter changes in 15 individuals with PWS (17-30 years) and 15 age-and-gender-matched controls. Whole-brain voxel-wise statistical analysis of FA was carried out using tract-based spatial statistics (TBSS). Significantly decreased fractional anisotropy was found localized to the left hemisphere in individuals with PWS within the splenium of the corpus callosum, the internal capsule including the posterior thalamic radiation and the inferior frontal occipital fasciculus (IFOF). Reduced integrity of these white matter pathways in individuals with PWS may relate to orientating attention, emotion recognition, semantic processing, and sensorimotor dysfunction.

Brain structural alterations in obese children with and without Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a genetic imprinting disorder that is mainly characterized by hyperphagia and childhood obesity. Previous neuroimaging studies revealed that there is a significant difference in brain activation patterns between obese children with and without PWS. However, whether there are differences in the brain structure of obese children with and without PWS remains elusive. In the current study, we used T1-weighted and diffusion tensor magnetic resonance imaging to investigate alterations in the brain structure, such as the cortical volume and white matter integrity, in relation to this eating disorder in 12 children with PWS, 18 obese children without PWS (OB) and 18 healthy controls. Compared with the controls, both the PWS and OB groups exhibited alterations in cortical volume, with similar deficit patterns in 10 co-varying brain regions in the bilateral dorsolateral and medial prefrontal cortices, right anterior cingulate cortex, and bilateral temporal lobe. The white matter integrities of the above regions were then examined with an analysis method based on probabilistic tractography. The PWS group exhibited distinct changes in the reduced fractional anisotropy of white matter fibers connected to the co-varying regions, whereas the OB group did not. Our findings indicated that PWS and OB share similar gray matter alterations that are responsible for the development of eating disorders. Additionally, the distinct white matter alterations might explain the symptoms associated with food intake in PWS, including excessive hyperphagia and constant hunger. Hum Brain Mapp 38:4228-4238, 2017. © 2017 Wiley Periodicals, Inc.

Craniofacial morphology in pediatric patients with Prader-Willi syndrome: a retrospective study.

OBJECTIVE: To investigate craniofacial characteristics in pediatric patients with Prader-Willi syndrome (PWS). SETTING AND SAMPLE POPULATION: A retrospective sample of 20 consecutive patients with PWS who had lateral and antero-posterior (AP) cephalograms (14 males and six females; average age 10.2 ± 3 years) was compared to 20 controls matched for age and sex (14 males and six females; average age 10.5 ± 3.7 years). MATERIALS AND METHODS: Cephalometric skeletal measurements were performed twice at a 1-week interval by one calibrated operator, and random error was calculated using Dahlberg's formula. Mean values and standard deviations were computed for all variables. Student's t-test for independent samples was used to determine significant differences between PWS and controls. The level of significance was set at p < 0.05. RESULTS: Cephalometric values for the length of the maxilla (p < 0.01), mandibular length (p < 0.05) at both the ramus (p < 0.05) and the mandibular body (p < 0.01), and posterior and anterior facial height (p < 0.01) were significantly lower in patients with PWS compared to controls. The AP cephalometric analysis revealed a significant reduction (p < 0.01) in maxillary skeletal width, mandibular skeletal width, and interzygomatic distance. CONCLUSIONS: Pediatric patients with PWS seem to have a general reduction in certain craniofacial skeletal parameters (i.e., maxillary and mandibular length) compared to controls, but this study did not assess the overall craniofacial characteristics.

Does segmental body composition differ in women with Prader-Willi syndrome compared to women with essential obesity?

BACKGROUND: Subjects with Prader-Willi syndrome (PWS) have a higher fat mass and a lower fat-free mass compared to subjects with essential obesity. However, few data are presently available on the segmental body composition (BC) of PWS subjects. AIM: To evaluate whether women with PWS and women with essential obesity, matched for age and percent body fat, differ in segmental fat distribution and surrogate markers of cardiometabolic disease (CMD). SUBJECTS AND METHODS: 35 women with PWS and 50 women with essential obesity were matched for age and percent body fat using coarsened exact matching. BC was measured by dual-energy X-ray absorptiometry. Oral glucose tolerance testing and measurements of cholesterol, triglycerides, C-reactive protein, and blood pressure were performed. Comparisons between PWS and obese women were performed using generalized linear models. RESULTS: Trunk fat was lower in PWS than in obese women on both absolute [-7.3 (95% confidence interval -9.4 to -5.2) kg] and relative [-4.1 (-6.9 to -1.4)% of body fat] grounds. PWS and obese women had similar surrogate markers of CMD, with the exception of HDL-cholesterol, which was higher in PWS women. CONCLUSION: Trunk fat is lower in obese women with PWS than in those with essential obesity. Surrogate markers of CMD are, however, mostly similar in the two groups.

Expanded Prader-Willi syndrome due to chromosome 15q11.2-14 deletion: report and a review of literature.

We report on a male infant with de novo unbalanced t(5;15) translocation resulting in a 17.23 Mb deletion within 15q11.2-q14 and a 25.12 kb deletion in 5pter. The 15q11.2-q14 deletion encompassed the 15q11.2-q13 Prader-Willi syndrome (PWS) critical region and the recently described 15q13.3 microdeletion syndrome region while the 5pter deletion contained no RefSeq genes. From our literature review, patients with similar deletions in chromosome 15q exhibit expanded phenotype of severe developmental delay, protracted feeding problem, absent speech, central visual impairment, congenital malformations and epilepsy in addition to those typical of PWS. The patient reported herein had previously unreported anomalies of mega cisterna magna, horseshoe kidney and the rare neonatal interstitial lung disease known as pulmonary interstitial glycogenosis. Precise breakpoint delineation by microarray is useful in patients with atypical PWS deletions to guide investigation and prognostication.

Can fetal ultrasound result in prenatal diagnosis of Prader-Willi syndrome?

OBJECTIVE: To define fetal ultrasound characteristics triggering an antenatal diagnosis of Prader Willi syndrome (PWS). METHODS: Retrospective analysis of sonographic characteristics retrieved from obstetric ultrasound records. All children (n=11) had a postnatal genetically confirmed diagnosis of PWS. RESULTS: All patients (n=11) showed at least one aspecific abnormality on prenatal ultrasound. Ten out of eleven (90.9 %) had decreased fetal movements, 7 (63.6%) presented in breech position, 7 (63.6%) had severe intra-uterine growth restriction (<5th centile) and 4 (36.4%) showed a polyhydramnios. Immobile flexed limbs and clenched hands were seen in one patient (9.1%). Severe growth restriction combined with polyhydramnios favors the diagnosis in 3/11 cases. CONCLUSION: Prenatal sonographic phenotype of PWS includes decreased fetal movements, fetal malpresentation, severe intra-uterine growth restriction and polyhydramnios. These findings are not specific to PWS, but the combination of some of them (especially severe intra-uterine growth restriction and polyhydramnios) can prompt clinicians to perform invasive testing leading to a molecular cytogenomic diagnosis prenatally.

Plantar Flexor Function in Adults with and without Prader-Willi Syndrome.

PURPOSE: Prader-Willi Syndrome (PWS) is a form of congenital obesity characterized by excessive body fat, hypotonia, muscle weakness, and physical/cognitive disability. However, the sources of muscle dysfunction and their contribution to mobility are unclear. The purposes of this study were to 1) compare plantar flexor function between adults with and without PWS; and 2) to examine the relationship between plantar flexor function and gait speed in adults with PWS. METHODS: Participants included 10 adults with PWS, 10 adults without PWS and with obesity, and 10 adults without PWS and without obesity (matched on age and sex). Plantar flexor function was assessed using isokinetic dynamometry (peak torque [PT], early/late rate of torque development [RTD]), Hoffman reflex (H/M ratio), ultrasound imaging (cross-sectional area [CSA], echo intensity, pennation angle, and fascicle length), and peak propulsive force and plantar flexor moment during gait. Outcomes were compared between groups using one-way MANOVA. Associations between plantar flexor outcomes and gait speed were assessed using Pearson correlation in the PWS group. RESULTS: Adults with PWS had lower absolute and normalized early RTD, and lower H/M ratio than controls with and without obesity; lower absolute PT and late RTD than controls with obesity (all P < 0.05). Cross-sectional area, propulsive force, and plantarflexor moment were lower, and echo intensity was higher, in adults with PWS compared with controls without obesity (all P < 0.05). Greater absolute PT (r = 0.64), absolute early RTD (r = 0.62), absolute late RTD (r = 0.64), gastrocnemii CSA (r = 0.55), and propulsive force (r = 0.58) were associated with faster gait speed (all P < 0.05). CONCLUSIONS: Adults with PWS have impaired plantar flexor function likely attributable to reduced neuromuscular function and altered muscle morphology, which are associated with slower gait speeds.

Congenital hypothyroidism due to ectopic sublingual thyroid gland in Prader-Willi Syndrome: a case report.

BACKGROUND: Thyroid gland disorders are variably associated with Prader-Willi syndrome (PWS). Many of the clinical features in newborns with PWS are similar to those found in congenital hypothyroidism (CH). CASE PRESENTATION: We report a case of a girl with CH and PWS. At the age of 9 months CH caused by an ectopic sublingual thyroid was diagnosed, and hormone replacement therapy was started. In spite of this treatment a decrease in growth velocity, weight excess and delayed development were observed. At the age of 9 years PWS was suspected on the basis of phenotype and genetic tests confirmed a maternal uniparental disomy of chromosome 15. This is the second reported case of hypothyroidism due to an ectopic sublingual thyroid gland in PWS suggesting that, although rare, an association between CH and PWS may exist. In our case diagnosis of PWS was delayed because mental retardation, hypotonia, obesity and short stature were initially attributed to hypothyroidism. CONCLUSIONS: In this context PWS should be considered in obese children with CH who do not improve adequately with l-thyroxine therapy. Also, thyroid function in all PWS children should be assessed regularly in order to avoid delayed diagnosis of hypothyroidism.

Aberrant White Matter Microstructure in Children and Adolescents With the Subtype of Prader-Willi Syndrome at High Risk for Psychosis.

Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder caused by loss of the paternal 15q11.2-q13 locus, due to deletion (DEL), maternal uniparental disomy (mUPD), or imprinting center defects. Individuals with mUPD have up to 60% risk of developing psychosis in early adulthood. Given the increasing evidence for white matter abnormalities in psychotic disorders, we investigated white matter microstructure in children and adolescents with PWS, with a particular emphasis on the DEL and mUPD subtypes. Magnetic resonance diffusion weighted images were acquired in 35 directions at 3T and analyzed using fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD) values obtained by tract-based spatial statistics (TBSS) in 28 children and adolescents with PWS and 61 controls. In addition, we employed a recently developed white matter pothole approach, which does not require local FA differences to be spatially co-localized across subjects. After accounting for age and gender, individuals with PWS had significantly lower global FA and higher MD, compared with controls. Individuals with mUPD had lower FA in multiple regions including the corpus callosum, cingulate, and superior longitudinal fasciculus and larger potholes, compared with DEL and controls. The observed differences in individuals with mUPD are similar to the white matter abnormalities in individuals with psychotic disorders. Conversely, the subtle white matter abnormalities in individuals with DEL are consistent with their substantially lower risk of psychosis. Future studies to investigate the specific neurobiological mechanism underlying the differential psychosis risk between the DEL and mUPD subtypes of PWS are highly warranted.

The impact of growth hormone/insulin-like growth factor-I axis and nocturnal breathing disorders on cardiovascular features of adult patients with Prader-Willi syndrome.

CONTEXT: Adult patients with Prader-Willi syndrome (PWS) are prone to develop obesity, GH deficiency (GHD), and their related complications, with cardiopulmonary failure explaining more than half of PWS fatalities. OBJECTIVE AND STUDY PARTICIPANTS: This study was undertaken to examine the effect of GHD and sleep breathing disorders on cardiovascular risk factors and heart features of 13 PWS (age 26.9 +/- 1.2 yr) and 13 age-, gender-, and body mass index-matched obese individuals (age 26.2 +/- 0.8 yr). RESULTS: Compared with controls, PWS patients had lower GH response to arginine+GHRH, IGF-I levels, triglycerides, total and LDL-cholesterol, insulin, and insulin resistance measured by a homeostatic model approach. Dual-energy x-ray absorptiometry, abdominal computed tomography scans, and polysomnography revealed a greater fat mass, similar abdominal fat, but greater sleep breathing disorders in PWS than obese subjects. Echocardiography showed no systolic or diastolic alteration, although PWS had lower left ventricle (LV) mass (135.7 +/- 7.7 vs. 163.5 +/- 8.4 g, P < 0.05) and near significantly lower values of LV end-diastole diameter (P = 0.08), compared with obese controls. Baseline radionuclide angiography documented comparable values of systolic and diastolic values between groups. However, adrenergic stimulation with dobutamine caused a lower increase of LV ejection fraction (71.9 +/- 1.9 vs. 76.3 +/- 1.2%, P < 0.05) and heart rate (103 +/- 6.9 vs. 128 +/- 2.8 beats/min, P < 0.05) in PWS than obese individuals. By multivariate analysis, nocturnal oxygen desaturation and IGF-I levels were main significant predictors of LV mass and heart rate in PWS patients. CONCLUSIONS: PWS differs from simple obesity by a healthier metabolic profile, impaired nocturnal breathing, decreased heart geometry, and systolic and chronotropic performance. GHD and the predictive role of IGF-I on structural and functional heart parameters suggest a GH/IGF-I-mediated control of cardiac risk in PWS.

Long-term echocardiographic and cardioscintigraphic effects of growth hormone treatment in adults with Prader-Willi syndrome.

CONTEXT: In Prader-Willi syndrome (PWS), an altered GH secretion has been related to reduced cardiac mass and systolic function compared to controls. OBJECTIVE: The objective was to evaluate the cardiovascular response to a 4-year GH therapy in adult PWS patients. STUDY PARTICIPANTS: Study participants were nine severely obese PWS adults (three females, six males) and 13 age-, gender-, and body mass index-matched obese controls. METHODS: In an open-label prospective study, assessment of endocrine parameters and metabolic outcome, whole-body and abdominal fat scans, echocardiography, and radionuclide angiography in unstimulated and dobutamine-stimulated conditions were conducted at baseline and after 1 and 4 years of GH treatment. RESULTS: GH treatment increased IGF-1 (P < .0001), decreased C-reactive protein levels (P < .05), improved visceral fat mass (P < .05), and achieved near-significant changes of fat and fat-free body mass in PWS patients. Left ventricle mass indexed by fat mass increased significantly after 1 and 4 years of GH therapy (P < .05) without evident abnormalities of diastolic function, while a trend toward a reduction of the ejection fraction was documented by echocardiography (P = .054). Radionuclide angiography revealed stable values throughout the study of both the left and right ventricle ejection fractions, although this was accompanied by a statistically nonsignificant reduction of the left ventricle filling rate. A positive association between lean body mass and left ventricle ejection fraction was evident during the study (P < .05). CONCLUSIONS: GH therapy increased the cardiac mass of PWS adults without causing overt abnormalities of systolic and diastolic function. Although the association between lean mass and left ventricle ejection fraction during GH therapy corroborates a favorable systemic outcome of long-term GH treatment in adults with PWS, subtle longitudinal modifications of functional parameters advocate appropriate cardiac monitoring in the long-term therapeutic strategy for PWS.

[Cytogenetic and clinical aspects of Prader-Willi syndrome]. / Contributo alla conoscenza degli aspetti citogenetici e clinici della sindrome di Prader-Willi.

Two male nonconsanguineous cases (aged 4 years) of Prader-Willi syndrome are clinically and cytologically studied. Both had obesity, marked hypogonadism, reduced head circumference, psychomotor impairment, hypotonia, tooth decay, small hands and feet, immature EEG. Case 1 showed a "de novo" translocation 7;15 and case 2 showed a normal karyotype. According to various authors, many cases of Prader-Willi syndrome show the presence of a translocation of chromosome 15 onto an autosome or X chromosome. This is the first observation of chromosome 7 involvement in this translocation.

Dual-energy X-ray absorptiometry is a valid method to estimate visceral adipose tissue in adult patients with Prader-Willi syndrome during treatment with growth hormone.

CONTEXT: Visceral adipose tissue (VAT) is established as a risk factor for type 2 diabetes and cardiovascular disease, but the radiation exposure and cost of computed tomography (CT) measurements limits its daily clinical use. OBJECTIVE: The main objective of this study was to compare the degree of agreement between VAT measurements by a new dual-energy X-ray absorptiometry (DXA) application and one of the standard methods, CT, in a population of patients with Prader-Willi syndrome (PWS) before and after GH treatment. Furthermore, we tested whether VAT estimations by these two methods are equivalent in assessing the metabolic risk in this population. DESIGN AND PATIENTS: Data from the Norwegian population of a multicenter study in adults with genetically proven PWS were used. Subjects with complete anthropometry, biochemical, and imagistic measurements at all study visits (baseline and after 12 and 24 months of GH treatment) (n = 14, six men) were included. VAT was quantified both using CT scans (GE Lightspeed 16 Pro) of the abdomen at L2-L3 level and a total body DXA scan (GE Healthcare Lunar Prodigy). RESULTS: VAT DXA was strongly associated with VAT CT at baseline (r = 0.97) and after 12 (r = 0.90) and 24 months (r = 0.89) of GH treatment (all P < .001). We found moderate to strong positive correlations between VAT by both methods, and blood pressure, weight, body mass index, waist circumference, glucose metabolism, and other fat depots (arms, legs, android, trunk, total body) but no association with age, gender, blood lipids, and IGF-I. Adiponectin was negatively associated with the amount of VAT. At baseline, the highest correlation with homeostasis model assessment of insulin resistance (HOMA-IR) was found for VAT DXA (r = 0.76, P = .001) and VAT CT (r = 0.75, P = .002), respectively. CONCLUSION: VAT can be accurately estimated by DXA, in patients with PWS, and might contribute to the assessment of the metabolic risk.