Intervención multidisciplinaria en paciente diagnosticado con el síndrome de Prader-Will / Interdisciplinary intervention in a pacient diagnosed with Prader-Willi síndrome

Introducción: El síndrome de Prader-Willi es una enfermedad genética, causada por deleciones de novo en la región 15q11q13 en el cromosoma paterno. Se caracteriza por falta de saciedad que conduce a obesidad mórbida, trastornos del comportamiento, discapacidad intelectual, baja estatura e hipogonadismo. Objetivo: Describir los resultados obtenidos del análisis e intervención multidisciplinar realizados en paciente diagnosticado con el síndrome de Prader-Willi. Presentación del caso: Análisis de caso clínico en menor de 8 años, sexo masculino, diagnosticado con síndrome de Prader-Willi, a través de intervención multidisciplinaria realizado en tres momentos: evaluación, diagnóstico e intervención con enfoque cognitivo conductual. Conclusiones: Las estrategias adoptadas generaron cambios significativos en el contexto familiar y social, entre ellas, apropiación de las recomendaciones suministradas, adopción de factores protectores, identificación de roles y optimización en la adherencia farmacológica. La atención a estas consideraciones proporciona mejoras, que apuntan a la calidad de vida y clínica del paciente(AU)

Introduction: Prader-Willi syndrome is a genetic disease caused by de novo deletions in the 15q11q13 region in the paternal chromosome. It is characterized by lack of satiety leading to morbid obesity, behavioral disorders, intellectual disability, short height and hypogonadism. Objective: To describe the results obtained from the multidisciplinary analysis and intervention performed in a patient diagnosed with Prader-Willi syndrome. Presentation of the clinical case: Clinical case analysis in an 8 years old child, male sex, diagnosed with Prader-Willi syndrome through a multidisciplinary intervention performed in three moments: assessment, diagnosis and intervention with cognitive behavioral approach. Conclusions: The strategies adopted generated significant changes in the social and family context, family´s appropriation of the recommendations provided, adoption of protective factors, roles identification and improving of adherence to treatment. By taking into account this considerations, improvements lead to clinic and life quality of the patient(AU)

Prevalence of Prader-Willi syndrome among infants with hypotonia.

OBJECTIVE: To investigate the prevalence of Prader-Willi syndrome (PWS) in infants with hypotonia between the ages of 0 and 2 years. STUDY DESIGN: Karyotyping studies were performed in all infants with hypotonia. The study group was composed of infants with hypotonia for whom the karyotyping was found to be normal. Fluorescence in situ hybridization and methylation analysis were performed simultaneously in the study group. Molecular studies for uniparental disomy were undertaken in the patients without deletions with an abnormal methylation pattern. RESULTS: Sixty-five infants with hypotonia with a mean age of 8 months were enrolled. A deletion was detected in 6 patients by fluorescence in situ hybridization analysis. Only 1 patient had no deletion but had an abnormal methylation pattern. A maternal uniparental disomy was observed in this patient. PWS was diagnosed in 10.7 % (7/65) of the infants with hypotonia. CONCLUSION: The prevalence of PWS syndrome is high among infants with hypotonia. PWS should be considered by pediatricians and neonatologists in the differential diagnosis of all newborns with hypotonia. Early diagnosis of PWS is important for the management of these patients.

Change in prevalence of congenital defects in children with Prader-Willi syndrome.

OBJECTIVE: The aim of this study was to assess the prevalence of congenital defects observed in patients with Prader-Willi syndrome (PWS) and to compare this prevalence with that described in the general population. In addition, these findings were correlated with the different etiologic subtypes. METHODS: A total of 180 children with PWS followed for 13 years were included in this study. Diagnosis was confirmed by the methylation test, and genetic subtypes were established by using fluorescence in situ hybridization or multiplex ligation-dependent probe amplification and microsatellite analyses. The prevalence of congenital defects was compared with national and international registries of congenital defects in the general population (Estudio Colaborativo Latinoamericano de Malformaciones Congénitas, European Surveillance of Congenital Anomalies, and the New York Registry). RESULTS: Twenty-two percent of the patients presented congenital defects with a risk of 5.4 to 18.7 times higher than that of the general population. The most frequent congenital defects were heart defects, renoureteral malformations, vertebral anomalies, hip dysplasia, clubfoot, and agenesis/hypoplasia of the corpus callosum. Each of these congenital defects was significantly more frequent in the children with PWS than in the general population. The congenital heart defects were more frequent in girls than in boys with PWS. No significant differences were found when the defects were correlated with the different etiologic subtypes. CONCLUSIONS: An increased prevalence of congenital defects was found in our PWS patients. This finding suggests the need for further studies in PWS children that allow physicians to detect the congenital defects found in this series and, thus, to anticipate complications, with the ultimate aim of enhancing the management of PWS patients.

Definable somatic disorders in overweight children and adolescents.

OBJECTIVE: To analyze the frequencies and clinical presentation of definable somatic disorders in children who are overweight. STUDY DESIGN: We assessed prospectively 1405 children aged 4 to 16 years who were overweight and came to our specialized clinic for endocrinology and obesity with a standardized diagnostic procedure. In a subgroup of 223 children, we sought mutations in the melanocortin-4-receptor gene (MC4R). RESULTS: Endocrine or syndromal disorders were diagnosed in 13 children (<1%; 4 with hypothyroidism, 1 with Cushing's syndrome, 1 with growth hormone deficiency, 2 with pseudohypoparathyroidism, 1 with pseudopseudohypoparathyroidism, 2 with Prader-Willi syndrome, 1 with Bardet-Biedl syndrome, 1 with Klinefelter syndrome). A total of 85% of these children had short stature, in marked contrast to only 0.6% of the other children. Moderately elevated thyrotropin and cortisol concentrations were observed in 4% and 5%, respectively, of all children. Non-synonymous MC4R mutations were found in 6% of the children. CONCLUSIONS: In contrast to MC4R mutations, endocrine and clinically identifiable syndromal disorders were rare in children who were overweight and always associated with further symptoms. All children who are overweight with short stature or reduced growth velocity should be carefully examined for endocrine or syndromal disorders. A general screening with laboratory measurements cannot be recommended because thyrotropin and cortisol levels are frequently moderately elevated in children who are overweight, thus entailing further superfluous diagnostic procedures.

Neurocognitive findings in Prader-Willi syndrome and early-onset morbid obesity.

OBJECTIVES: To examine whether early-onset morbid obesity is associated with cognitive impairment, neuropathologic changes, and behavioral problems. STUDY DESIGN: This case-control study compared head MRI scans and cognitive, achievement, and behavioral evaluations of subjects with Prader-Willi syndrome (PWS), early-onset morbid obesity (EMO), and normal-weight sibling control subjects from both groups. Head MRI was done on 17 PWS, 18 EMO, and 21 siblings, and cognitive, achievement, and behavioral evaluations were done on 19 PWS, 17 EMO, and 24 siblings. RESULTS: The mean General Intellectual Ability score of the EMO group was 77.4 +/- 17.8; PWS, 63.3 +/- 14.2; and control subjects, 106.4 +/- 13.0. Achievement scores for the three groups were EMO, 78.7 +/- 18.8; PWS, 71.2 +/- 17.0; and control subjects, 104.8 +/- 17.0. Significant negative behaviors and poor adaptive skills were found in the EMO group. White matter lesions were noted on brain MRI in 6 subjects with PWS and 5 with EMO. None of the normal-weight control subjects had these findings. CONCLUSIONS: Individuals with EMO have significantly lower cognitive function and more behavioral problems than control subjects with no history of childhood obesity. Both EMO and PWS subjects have white matter lesions on brain MRI that have not previously been described.

Sleep-disordered breathing in Prader-Willi syndrome and its association with neurobehavioral abnormalities.

OBJECTIVES: To determine the prevalence and type of sleep-disordered breathing among patients with Prader-Willi syndrome (PWS) and its relationship to such neurobehavioral abnormalities as mental retardation, obsessive-compulsive behavior, and conduct disorders. STUDY DESIGN: Polysomnography (PSG) studies were conducted in 13 unselected subjects with PWS (age 1.5 to 28 years). PSG results were compared with tests of behavior and cognition (Development Behavior Checklist [DBC], Auditory Continuous Performance Test [ACPT], and Wechsler Intelligence Scale appropriate for age). RESULTS: Nine of 13 (69%) subjects had > 10 apneas and hypopneas per hour of sleep. Apart from a 2-year-old subject with normal body weight who demonstrated severe central hypopnea in rapid eye movement sleep, the sleep-breathing disturbance was due to upper airway obstruction. Age-adjusted body mass index was associated with more severe hypoxemia during sleep (min SaO2, r = -.87, P < .005) and more sleep disruption (arousals/hour of sleep, r = .62, P < .05; sleep efficiency, r = -.66, P < .05). Increasing severity of obstructive sleep apnea (OSA) or sleep disturbance was associated with daytime inactivity/sleepiness and autistic-relating behavior (DBC) and with impulsiveness (ACPT). Unexpectedly, sleep hypoxemia appeared to be predictive of increased performance IQ. CONCLUSIONS: OSA is prevalent among subjects with PWS and is associated with increased body mass, daytime inactivity/ sleepiness, and some behavioral disturbances.

Results of biliopancreatic diversion in two patients with Prader-Willi syndrome.

Prader-Willi Syndrome (PWS) is a genetic disorder characterized by hypotonia, mental retardation or learning disability, hyperphagia and compulsive eating due to hypothalamic dysfunction. Obesity is a major cause of increased morbidity and mortality among patients with PWS. Gastric restrictive surgery has been associated with partial breakdown of the staple-line in PWS. We report two patients with PWS associated with morbid obesity and obstructive sleep apnea who underwent biliopancreatic diversion (BPD). A 27-year-old male with BMI 52 kg/m(2) and a 20 year-old female with BMI 64 kg/m(2) underwent BPD. No perioperative complications were observed. After BPD, the male's BMI was 36.7 kg/m(2) at 12 months and the female's BMI was 48.4 kg/m(2) at 28 months, with excess weight loss 58% and 48%, respectively. They developed loose stools associated with eating. These patients have shown a considerable improvement in hypersomnia and respiratory difficulties. BPD proved to be an effective approach to weight loss in PWS, resulting in improvement of sleep apnea, behavior problems and quality of life.

Síndrome de Prader-Willi / Case report: Prader-willi: syndrome

Objetivo: o presente artigo objetiva relatar um caso de síndrome de Prader-Willi (SPW). Discussão do caso: paciente de 15 anos, sexo masculino, que se apresentou com as principais características da síndrome: a obesidade móbida, baixa estatura, hipogononadismo e fáceis característica . K. B.R. teve seu diagnóstico suspeito com 4 dias de vida, quando apresentou reflexos diminuídos, hipotonia, choro fraco e dificuldade em mamar. Com aproximadamente 2 anos, iniciou exagerado ganho de oeso, justificado pela sua fome insaciável. Aos 5 anos de idade fez-se o diagnóstico clínico de SPW, que posteriormente foi confirmado pela avaliação genética. Comentários: a SPW é um distúrbio neurocomportamental que geralmente surge por uma deleção proximal do cromossomo 15 durante a gametogênese paterna. A incidência varia de 1 caso em 25.000 até 1 caso em 10.000 nascidos vivos. O quadro clínico é caracterizado por hipotonia neonatal, retardo mental moderado, hiperfagia e obesidade precoce, hipogonadismo, acromicria e fáceis característca. O diagnóstico é feito clinicamente, podendo ser confirmado pela análise do segmento cromossômico 15q11-q13, por meio da metilação ou da hibridização in situ. Não há tratamento específico eficaz. Atualmente, a administração de hormônio do crescimento é a opção mais aceita.

Sindrome de Prader-Labhart-Willi: clínica y citogenética / Prader-labhart-willi syndrome: clinic and citogenetics

El Sindrome de Prader-labhart-Willi (SPLW), se caracteriza por hipotonía infantil, hipogonadismo, retraso en el desarrollo psicomotor, seguido de hiperfagia, instauración de obesidad, corta estatura, anormal función intelectual como del comportamiento y un leve dismorfismo accesorio. La etiología permanece aún sin determinar, sin embargo se han encontrado alteraciones en el cromosoma 15 en un porcentaje variable de pacientes con SPLW. para detectar pacientes afectados con este sindrome, se evaluaron 5,080 individuos con retardo mental que acuden a los Centros de Educación Especial (C.E.E.) de Lima y Callao. Se encontraron 5 casos con el cuadro completo cuyas características concuerdan muy bien con lo reportado en la literatura; además utilizando la técnica de bandeo cromosómico no se hallaron anomalías en sus cariotipos. La baja incidencia de SPLW encontrada, se atribuye a la excesiva rigurosidad en los criterios diagnósticos y a la inasistencia de estos pacientes a lo C.E.E. causada por sus peculiares problemas de comportamiento. Se realiza una revisión bibliográfica de la entidad y se concluye que debe ampliarse el espectro de severidad de este sindrome al hacer el diagnóstico