Prader-Willi syndrome: consensus diagnostic criteria.

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.

Rumination and vomiting in Prader-Willi syndrome.

Inability to vomit has been cited as characteristic of Prader-Willi syndrome (PWS). Although post-prandial vomiting after gastric by-pass surgery has been reported, neither vomiting under "typical" circumstances or rumination have been described. Prompted by the discovery of several cases of vomiting and rumination, a questionnaire was sent to members of the PWS Association. Approximately 36% (113/313) of affected individuals reportedly experienced at least one episode of vomiting. Induced vomiting was unsuccessful in 9 of 14 cases in whom results were known. However, no complications of Ipecac were reported. We suggest that there is an alteration in the physiologic set-point at which vomiting occurs, leading to a decreased propensity to vomit. Liberal and strict definitions of rumination yielded 15.7% and 10.2% positive responses, respectively. Rumination was associated with a history of vomiting. Enamel deterioration consistent with rumination has been observed, and such changes should be looked for in all PWS children. In several instances, rumination was found to decrease when very strict weight control was lessened. Certain individuals may ruminate under too strict a weight control program, and weight control goals should be evaluated to achieve a reasonable compromise between ideal weight and obesity. Vomiting and rumination do not rule out the diagnosis of PWS.

Clinical spectrum and molecular diagnosis of Angelman and Prader-Willi syndrome patients with an imprinting mutation.

Recent studies have identified a new class of Prader-Willi syndrome (PWS) and Angelman syndrome (AS) patients who have biparental inheritance, but neither the typical deletion nor uniparental disomy (UPD) or translocation. However, these patients have uniparental DNA methylation throughout 15q11-q13, and thus appear to have a mutation in the imprinting process for this region. Here we describe detailed clinical findings of five AS imprinting mutation patients (three families) and two PWS imprinting mutation patients (one new family). All these patients have essentially the classical clinical phenotype for the respective syndrome, except that the incidence of microcephaly is lower in imprinting mutation AS patients than in deletion AS patients. Furthermore, imprinting mutation AS and PWS patients do not typically have hypopigmentation, which is commonly found in patients with the usual large deletion. Molecular diagnosis of these cases is initially achieved by DNA methylation analyses of the DN34/ZNF127, PW71 (D15S63), and SNRPN loci. The latter two probes have clear advantages in the simple molecular diagnostic analysis of PWS and AS patients with an imprinting mutation, as has been found for typical deletion or UPD PWS and AS cases. With the recent finding of inherited microdeletions in PWS and AS imprinting mutation families, our studies define a new class of these two syndromes. The clinical and molecular identification of these PWS and AS patients has important genetic counseling consequences.

A community outreach program for individuals with Prader-Willi syndrome.

Individuals with Prader-Willi Syndrome (PWS) face life with multifaceted problems that hinder adaptation to daily life. Helping this population presents a major challenge to health professionals. With few exceptions, primary providers lack support systems essential for effective management. The Iowa Child Health Specialty Clinics (CHSC) has pioneered an outreach program for affected children, their families, and primary providers. Community-based services provided by a CHSC regional nurse and PWS consultant emphasize education, communication, networking services, case review, and pragmatic approaches to care. Satisfaction with initial outreach has been high. This discussion proposes to better prepare nurses to appreciate needs of individuals with PWS and their families and to function as coordinators of services.

Adults with Prader-Willi syndrome: a survey of 232 cases.

Older individuals with Prader-Willi syndrome have rarely been documented. This report describes the physical characteristics, health problems, cognition, psychosocial adjustment and impact on the family of 232 adults with the syndrome, ranging in age from 16 to 64 years. The sample showed that Prader-Willi syndrome occurs with equal frequency in both sexes. Most were short, overweight, cognitively impaired, emotionally labile, had poor gross motor skills and were always hungry. Males were taller and heavier than females, and both sexes were far shorter and heavier than US norms. Micropenis and cryptorchidism in males and primary amenorrhea, late menarche and irregular menstrual cycles in females indicated hypogenitalism in both sexes. Of 106 with chromosome analysis, 54 had an abnormality on chromosome 15, primarily a deletion; the others had normal chromosomes.