Search

ObjectiveThe goal of this study was to generate and report standardized growth curves for weight, height, head circumference, and BMI for non-growth hormone-treated white male and female US subjects with Prader-Willi syndrome (PWS) between 3 and 18 years of age and develop standardized growth charts.MethodsAnthropometric measures (N = 133) were obtained according to standard methods from 120 non-growth hormone-treated white subjects (63 males and 57 females) with PWS between 3 and 18 years of age. Standardized growth curves were developed for the third, 10th, 25th, 50th, 75th, 90th, and 97th percentiles by using the LMS method for weight, height, head circumference, and BMI for PWS subjects along with the normative third, 50th, and 97th percentiles from national and international growth data. The LMS smoothing procedure summarized the distribution of the anthropometric variables at each age using three parameters: power of the Box-Cox transformation λ (L), median μ (M) and coefficient of variation δ (S).ResultsWeight, height, head circumference, and BMI standardized growth charts representing 7 percentile ranges were developed from 120 non-growth hormone-treated white male and female US subjects with PWS (age range: 3-18 years) and normative third, 50th, and 97th percentiles from national and international data.ConclusionsWe encourage the use of syndrome-specific growth standards to examine and evaluate subjects with PWS when monitoring growth patterns and determining nutritional and obesity status. These variables can be influenced by culture, individual medical care, diet intervention, and physical activity plans.

ObjectiveTo generate and report standardized growth curves for weight, length, head circumference, weight/length, and BMI for non-growth hormone-treated white infants (boys and girls) with Prader-Willi syndrome (PWS) between 0 and 36 months of age. The goal was to monitor growth and compare data with other infants with PWS.MethodsAnthropometric measures (N = 758) were obtained according to standard methods and analyzed from 186 non-growth hormone-treated white infants (108 boys and 78 girls) with PWS between 0 and 36 months of age. Standardized growth curves were developed and the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles were calculated by using the LMS (refers to λ, μ, and σ) smoothing procedure method for weight, length, head circumference, weight/length, and BMI along with the normative 50th percentile using Centers for Disease Control and Prevention national growth data from 2003. The data were plotted for comparison purposes.ResultsFive separate standardized growth curves (weight, length, head circumference, weight/length, and BMI) representing 7 percentile ranges were developed from 186 non-growth hormone-treated white male and female infants with PWS aged 0 to 36 months, and the normative 50th percentile was plotted on each standardized infant growth curve.ConclusionsWe encourage the use of these growth standards when examining infants with PWS and evaluating growth for comparison purposes, monitoring for growth patterns, nutritional assessment, and recording responses to growth hormone therapy, commonly used in infants and children with PWS.

Objective. To determine whether phenotypic differences exist among individuals with Prader-Willi syndrome with either type I or type II deletions of chromosome 15 or maternal disomy 15 leading to a better understanding of cause and pathophysiology of this classical genetic syndrome. Methods. We analyzed clinical, anthropometric, and behavioral data in 12 individuals (5 men, 7 women; mean age: 25.9 [+ or -] 8.8 years) with PWS and a type I (TI) deletion, 14 individuals (6 men, 8 women; mean age: 19.6 [+ or -] 6.5 years) with PWS and a type II (TII) deletion, and 21 individuals (10 men, 11 women; mean age: 23.6 [+ or -] 9.2 years) with PWS and maternal disomy 15 (UPD). The deletion type was determined by genotyping of DNA markers between proximal chromosome 15 breakpoints BP1 and BP2. TI deletions are ~500 kb larger than TII deletions. Several validated psychological and behavioral tests were used to assess phenotypic characteristics of individuals with PWS representing the 3 genetic subtypes. Results. Significant differences were found between the 2 deletion groups and those with UPD in multiple psychological and behavorial tests, but no differences were observed in other clinical or anthropometric data studied. Adaptive behavior scores were generally worse in individuals with PWS and the TI deletion, and specific obsessive-compulsive behaviors were more evident in the TI individuals compared with those with UPD. Individuals with PWS with TI deletions also had poorer reading and math skills as well as visual-motor integration. Conclusions. Our study indicates that individuals with TI deletion generally have more behavioral and psychological problems than individuals with the TII deletion or UPD. Four recently identified genes have been identified in the chromosome region between BP1 and BP2 with 1 of the genes (NIPA-1) expressed in mouse brain tissue but not thought to be imprinted. It may be important for brain development or function. These genes are deleted in individuals with TI deletion and are implicated in compulsive behavior and lower intellectual ability in individuals with TI versus TII. Pediatrics 2004; 113:565-573; Prader-Willi syndrome, type I and type II deletions, maternal disomy 15, clinical differences. ABBREVIATIONS. PWS, Prader-Willi syndrome; UPD, maternal disomy 15; AS, Angelman syndrome; BP, breakpoint; TI, type I; TII, type II; IQ, intelligence quotient; CBC, Child Behavior Checklist; Y-BOCS, Yale-Brown Obsessive-Compulsive Scale; VMI, visual-motor integration; SIB, self-injurious behavior., Prader-Willi syndrome (PWS) is a genetic disorder that results from the absence of normally active paternally expressed genes from the 15q11-q13 chromosome region. (1-3) A number of genes located in [...]

A set of diagnostic criteria may help with the diagnosis of Prader-Willi syndrome in children and adults. Prader-Willi syndrome is a genetic disorder that is often difficult to diagnose. These diagnostic criteria include two scoring systems: one system for infants younger than 36 months old and another system for children over three years old and adults. Diagnostic criteria for infants include reduced skeletal muscle tone and feeding problems. Other criteria include abnormal facial features, obesity, short stature, impaired gonad function, mental retardation and behavioral problems. Some of the characteristics of Prader-Willi syndrome change over time in different patients. There is no biological marker that can be used to diagnose individuals with suspected Prader-Willi syndrome. A set of diagnostic criteria may help standardize the diagnosis of Willi-Prader syndrome., The diagnosis of Prader-Willi syndrome (PWS) is based on clinical findings that change with age. Hypotonia is prominent in infancy. Obesity, mild mental retardation or learning disability, and behavior problems, especially in association with food and eating, result in a debilitating physical and developmental disability in adolescence and adulthood. No consistent biological marker is yet available for PWS in spite of recent research activity in cytogenetics and molecular genetics. Diagnostic criteria for PWS were developed, by consensus of seven clinicians experienced with the syndrome in consultation with national and international experts. Two scoring systems are provided: one for children aged 0 to 36 months and another one for children aged 3 years to adults. These criteria will aid in recognition of the syndrome in hypotonic infants and in obese, mildly retarded, behaviorally disturbed adolescents and adults. They will also ensure uniform diagnosis for future clinical and laboratory research in PWS. Pediatrics 1993;91:398-402; Prader-Willi syndrome, diagnostic criteria.

Standards (95th, 50th, and 5th percentiles) in fragile X syndrome for weight, height, head circumference, ear length, and testicular volume are reported. For comparison with fragile X syndrome standardized curves, normal control data from the literature were similarly plotted and curves produced. These standards reflect the physical parameters that are frequently abnormal in males with the fragile X syndrome and should be useful in the medical management of patients with this syndrome. The standards may also be used to help identify those individuals, particularly the younger males, for chromosome studies to confirm the clinical impression of the fragile X syndrome.

Prader-Willi syndrome is characterized by the loss of muscle tone during infancy, then later on, during early childhood, obesity, mental retardation, diminished pigmentation, small hands and feet, short height, impaired secretion from the ovaries and testes, and facial peculiarities. This disorder affects 1 in 16,000 infants and appears to result from a genetic defect. There is limited information about the growth of children with Prader-Willi syndrome. Certain anthropometric measurements were made in 71 children and adults under age 24 years with Prader-Willi syndrome in order to develop standards regarding growth. Weight, height, sitting height, three different head measurements, four hand and two foot measurements, and two skinfold measurements were made for each patient. The results were compared to data obtained from normal subjects. The anthropometric standards for Prader-Willi syndrome presented in this article should be useful in examining and comparing patients with this disorder and in the diagnosis of this syndrome in younger children. (Consumer Summary produced by Reliance Medical Information, Inc.)

Prader-Willi syndrome is a neurodevelopmental disorder that is characterized by infantile hypotonia, feeding difficulties, hypogonadism, mental deficiency, hyperphagia (leading to obesity in early childhood), learning problems, and behavioral difficulties. A paternal 15q11-q13 deletion is found in ~70% of patients with Prader-Willi syndrome, ~25% have uniparental maternal disomy 15, and the remaining 2% to 5% have imprinting defects. The proximal deletion breakpoint in the 15q11-q13 region occurs at 1 of 2 sites located within either of 2 large duplicons allowing for the identification of 2 deletion subgroups. The larger, type I (TI) deletion involves breakpoint 1, which is close to the centromere, whereas the smaller, type II (TII) deletion involves breakpoint 2, located ~500 kilobases distal to breakpoint 1. Breakpoint 3 is located at the distal end of the 15q11-q13 region and common to both typical deletion subgroups. Analyses of the genetic subtypes of Prader-Willi syndrome to date have primarily compared individuals with typical deletion and uniparental maternal disomy 15 without grouping the individuals with a deletion into TI or TII. Distinct differences have been reported between individuals with Prader-Willi syndrome resulting from deletion compared with uniparental maternal disomy 15 in physical, cognitive, and behavioral parameters. We previously presented the first assessment of clinical differences in individuals with Prader-Willi syndrome categorized as having type I or II deletions. Adaptive behavior, obsessive-compulsive behaviors, reading, math, and visual-motor integration assessments were generally poorer in individuals with Prader-Willi syndrome and the TI deletion compared with subjects with Prader-Willi syndrome with the TII deletion or uniparental maternal disomy 15. Four genes (NIPA1, NIPA2, CYFIP1, and GCP5) have been identified in the chromosomal region between breakpoints 1 and 2 and are implicated in compulsive behavior and lower intellectual ability observed in individuals with Prader-Willi syndrome with TI versus TII deletions. We quantified messenger-RNA levels of these 4 genes in actively growing lymphoblastoid cells derived from 8 subjects with Prader-Willi syndrome with the TI deletion (4 males, 4 females; mean: age 25.2 [+ or -] 8.9 years) and 9 with the TII deletion (3 males, 6 females; mean age: 19.5 [+ or -] 5.8 years). Messenger-RNA levels were correlated with validated psychological and behavioral scales administered by trained psychologists blinded to genotype status. Messenger RNA from NIPA1, NIPA2, CYFIP1, and GCP5 was reduced but detectable in the subjects with Prader-Willi syndrome with the TI deletion, supporting biallelic expression. For the most part, messenger-RNA values were positively correlated with assessment parameters, indicating a direct relationship between messenger-RNA levels and better assessment scores, with the highest correlation for NIPA2. The coefficient of determination indicated the quantity of messenger RNA of the 4 genes explained from 24% to 99% of the variation of the behavioral and academic parameters measured. By comparison, the coefficient of determination for deletion type alone explained 5% to 50% of the variation in the assessed parameters. Understanding the influence of gene expression on behavioral and cognitive characteristics in humans is in the early stage of research development. Additional research is needed to identify the function of these genes and their interaction with gene networks to clarify the potential role they play in central nervous system development and function. KEYWORDS. Prader-Willi syndrome, PWS, type I and II deletions, genotype-phenotype correlation, academic and behavioral assessment, gene expression. URL: www.pediatrics.org/cgi/doi/10.1542/peds.2006-0424